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Sample records for adult songbird brain

  1. A framework for integrating the songbird brain

    PubMed Central

    Smith, V.A.; Wada, K.; Rivas, M.V.; McElroy, M.; Smulders, T.V.; Carninci, P.; Hayashizaki, Y.; Dietrich, F.; Wu, X.; McConnell, P.; Yu, J.; Wang, P.P.; Hartemink, A.J.; Lin, S.

    2008-01-01

    Biological systems by default involve complex components with complex relationships. To decipher how biological systems work, we assume that one needs to integrate information over multiple levels of complexity. The songbird vocal communication system is ideal for such integration due to many years of ethological investigation and a discreet dedicated brain network. Here we announce the beginnings of a songbird brain integrative project that involves high-throughput, molecular, anatomical, electrophysiological and behavioral levels of analysis. We first formed a rationale for inclusion of specific biological levels of analysis, then developed high-throughput molecular technologies on songbird brains, developed technologies for combined analysis of electrophysiological activity and gene regulation in awake behaving animals, and developed bioinformatic tools that predict causal interactions within and between biological levels of organization. This integrative brain project is fitting for the interdisciplinary approaches taken in the current songbird issue of the Journal of Comparative Physiology A and is expected to be conducive to deciphering how brains generate and perceive complex behaviors. PMID:12471494

  2. Integrating Genomes, Brain and Behavior in the Study of Songbirds

    PubMed Central

    Clayton, David F.; Balakrishnan, Christopher N.; London, Sarah E.

    2010-01-01

    Songbirds share some essential traits but are extraordinarily diverse, allowing comparative analyses aimed at identifying specific genotype–phenotype associations. This diversity encompasses traits like vocal communication and complex social behaviors that are of great interest to humans, but that are not well represented in other accessible research organisms. Many songbirds are readily observable in nature and thus afford unique insight into the links between environment and organism. The distinctive organization of the songbird brain will facilitate analysis of genomic links to brain and behavior. Access to the zebra finch genome sequence will, therefore, prompt new questions and provide the ability to answer those questions. PMID:19788884

  3. Dopamine receptors in a songbird brain

    PubMed Central

    Kubikova, Lubica; Wada, Kazuhiro; Jarvis, Erich D

    2010-01-01

    Dopamine is a key neuromodulatory transmitter in the brain. It acts through dopamine receptors to affect changes in neural activity, gene expression, and behavior. In songbirds, dopamine is released into the striatal song nucleus Area X, and the levels depend on social contexts of undirected and directed singing. This differential release is associated with differential expression of activity-dependent genes, such as egr1 (avian zenk), which in mammalian brain are modulated by dopamine receptors. Here we cloned from zebra finch brain cDNAs of all avian dopamine receptors: the D1 (D1A, D1B, D1D) and D2 (D2, D3, D4) families. Comparative sequence analyses of predicted proteins revealed expected phylogenetic relationships, in which the D1 family exists as single exon and the D2 family exists as spliced exon genes. In both zebra finch and chicken, the D1A, D1B, and D2 receptors were highly expressed in the striatum, the D1D and D3 throughout the pallium and within the mesopallium, respectively, and the D4 mainly in the cerebellum. Furthermore, within the zebra finch, all receptors, except for D4, showed differential expression in song nuclei relative to the surrounding regions and developmentally regulated expression that decreased for most receptors during the sensory acquisition and sensorimotor phases of song learning. Within Area X, half of the cells expressed both D1A and D2 receptors, and a higher proportion of the D1A-only-containing neurons expressed egr1 during undirected but not during directed singing. Our findings are consistent with hypotheses that dopamine receptors may be involved in song development and social context-dependent behaviors. J. Comp. Neurol. 518:741–769, 2010. © 2009 Wiley-Liss, Inc. PMID:20058221

  4. Endocrine and social regulation of adult neurogenesis in songbirds.

    PubMed

    Balthazart, Jacques; Ball, Gregory F

    2016-04-01

    The identification of pronounced seasonal changes in the volume of avian song control nuclei stimulated the discovery of adult neurogenesis in songbirds as well as renewed studies in mammals including humans. Neurogenesis in songbirds is modulated by testosterone and other factors such as photoperiod, singing activity and social environment. Adult neurogenesis has been widely studied by labeling, with tritiated thymidine or its analog BrdU, cells duplicating their DNA in anticipation of their last mitotic division and following their fate as new neurons. New methods based on endogenous markers of cell cycling or of various stages of neuronal life have allowed for additional progress. In particular immunocytochemical visualization of the microtubule-associated protein doublecortin has provided an integrated view of neuronal replacement in the song control nucleus HVC. Multiple questions remain however concerning the specific steps in the neuronal life cycle that are modulated by various factors and the underlying cellular mechanisms. PMID:26996818

  5. Learning-related brain hemispheric dominance in sleeping songbirds

    PubMed Central

    Moorman, Sanne; Gobes, Sharon M. H.; van de Kamp, Ferdinand C.; Zandbergen, Matthijs A.; Bolhuis, Johan J.

    2015-01-01

    There are striking behavioural and neural parallels between the acquisition of speech in humans and song learning in songbirds. In humans, language-related brain activation is mostly lateralised to the left hemisphere. During language acquisition in humans, brain hemispheric lateralisation develops as language proficiency increases. Sleep is important for the formation of long-term memory, in humans as well as in other animals, including songbirds. Here, we measured neuronal activation (as the expression pattern of the immediate early gene ZENK) during sleep in juvenile zebra finch males that were still learning their songs from a tutor. We found that during sleep, there was learning-dependent lateralisation of spontaneous neuronal activation in the caudomedial nidopallium (NCM), a secondary auditory brain region that is involved in tutor song memory, while there was right hemisphere dominance of neuronal activation in HVC (used as a proper name), a premotor nucleus that is involved in song production and sensorimotor learning. Specifically, in the NCM, birds that imitated their tutors well were left dominant, while poor imitators were right dominant, similar to language-proficiency related lateralisation in humans. Given the avian-human parallels, lateralised neural activation during sleep may also be important for speech and language acquisition in human infants. PMID:25761654

  6. Learning-related brain hemispheric dominance in sleeping songbirds.

    PubMed

    Moorman, Sanne; Gobes, Sharon M H; van de Kamp, Ferdinand C; Zandbergen, Matthijs A; Bolhuis, Johan J

    2015-01-01

    There are striking behavioural and neural parallels between the acquisition of speech in humans and song learning in songbirds. In humans, language-related brain activation is mostly lateralised to the left hemisphere. During language acquisition in humans, brain hemispheric lateralisation develops as language proficiency increases. Sleep is important for the formation of long-term memory, in humans as well as in other animals, including songbirds. Here, we measured neuronal activation (as the expression pattern of the immediate early gene ZENK) during sleep in juvenile zebra finch males that were still learning their songs from a tutor. We found that during sleep, there was learning-dependent lateralisation of spontaneous neuronal activation in the caudomedial nidopallium (NCM), a secondary auditory brain region that is involved in tutor song memory, while there was right hemisphere dominance of neuronal activation in HVC (used as a proper name), a premotor nucleus that is involved in song production and sensorimotor learning. Specifically, in the NCM, birds that imitated their tutors well were left dominant, while poor imitators were right dominant, similar to language-proficiency related lateralisation in humans. Given the avian-human parallels, lateralised neural activation during sleep may also be important for speech and language acquisition in human infants. PMID:25761654

  7. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds

    PubMed Central

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D.

    2014-01-01

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

  8. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  9. What songbirds teach us about learning

    NASA Astrophysics Data System (ADS)

    Brainard, Michael S.; Doupe, Allison J.

    2002-05-01

    Bird fanciers have known for centuries that songbirds learn their songs. This learning has striking parallels to speech acquisition: like humans, birds must hear the sounds of adults during a sensitive period, and must hear their own voice while learning to vocalize. With the discovery and investigation of discrete brain structures required for singing, songbirds are now providing insights into neural mechanisms of learning. Aided by a wealth of behavioural observations and species diversity, studies in songbirds are addressing such basic issues in neuroscience as perceptual and sensorimotor learning, developmental regulation of plasticity, and the control and function of adult neurogenesis.

  10. How the songbird brain listens to its own songs

    NASA Astrophysics Data System (ADS)

    Hahnloser, Richard

    2010-03-01

    Songbirds are capable of vocal learning and communication and are ideally suited to the study of neural mechanisms of auditory feedback processing. When a songbird is deafened in the early sensorimotor phase after tutoring, it fails to imitate the song of its tutor and develops a highly aberrant song. It is also known that birds are capable of storing a long-term memory of tutor song and that they need intact auditory feedback to match their own vocalizations to the tutor's song. Based on these behavioral observations, we investigate feedback processing in single auditory forebrain neurons of juvenile zebra finches that are in a late developmental stage of song learning. We implant birds with miniature motorized microdrives that allow us to record the electrical activity of single neurons while birds are freely moving and singing in their cages. Occasionally, we deliver a brief sound through a loudspeaker to perturb the auditory feedback the bird experiences during singing. These acoustic perturbations of auditory feedback reveal complex sensitivity that cannot be predicted from passive playback responses. Some neurons are highly feedback sensitive in that they respond vigorously to song perturbations, but not to unperturbed songs or perturbed playback. These findings suggest that a computational function of forebrain auditory areas may be to detect errors between actual feedback and mirrored feedback deriving from an internal model of the bird's own song or that of its tutor.

  11. Impact of experience-dependent and -independent factors on gene expression in songbird brain.

    PubMed

    Drnevich, Jenny; Replogle, Kirstin L; Lovell, Peter; Hahn, Thomas P; Johnson, Frank; Mast, Thomas G; Nordeen, Ernest; Nordeen, Kathy; Strand, Christy; London, Sarah E; Mukai, Motoko; Wingfield, John C; Arnold, Arthur P; Ball, Gregory F; Brenowitz, Eliot A; Wade, Juli; Mello, Claudio V; Clayton, David F

    2012-10-16

    Songbirds provide rich natural models for studying the relationships between brain anatomy, behavior, environmental signals, and gene expression. Under the Songbird Neurogenomics Initiative, investigators from 11 laboratories collected brain samples from six species of songbird under a range of experimental conditions, and 488 of these samples were analyzed systematically for gene expression by microarray. ANOVA was used to test 32 planned contrasts in the data, revealing the relative impact of different factors. The brain region from which tissue was taken had the greatest influence on gene expression profile, affecting the majority of signals measured by 18,848 cDNA spots on the microarray. Social and environmental manipulations had a highly variable impact, interpreted here as a manifestation of paradoxical "constitutive plasticity" (fewer inducible genes) during periods of enhanced behavioral responsiveness. Several specific genes were identified that may be important in the evolution of linkages between environmental signals and behavior. The data were also analyzed using weighted gene coexpression network analysis, followed by gene ontology analysis. This revealed modules of coexpressed genes that are also enriched for specific functional annotations, such as "ribosome" (expressed more highly in juvenile brain) and "dopamine metabolic process" (expressed more highly in striatal song control nucleus area X). These results underscore the complexity of influences on neural gene expression and provide a resource for studying how these influences are integrated during natural experience. PMID:23045667

  12. Neurosteroid production in the songbird brain: a re-evaluation of core principles

    PubMed Central

    London, Sarah E.; Remage-Healey, Luke; Schlinger, Barney A.

    2009-01-01

    Concepts of brain-steroid signaling have traditionally placed emphasis on the gonads and adrenals as the source of steroids, the strict dichotomy of early developmental (“organizational”) and mature (“activational”) effects, and a relatively slow mechanism of signaling through intranuclear receptors. Continuing research shows that these concepts are not inaccurate, but they are certainly incomplete. In this review, we focus on the song control circuit of songbird species to demonstrate how each of these concepts is limited. We discuss the solid evidence for steroid synthesis within the brain (“neurosteroidogenesis”), the role of neurosteroids in organizational events that occur both early in development and later in life, and how neurosteroids can act in acute and non-traditional ways. The songbird model therefore illustrates how neurosteroids can dramatically increase the diversity of steroid-sensitive brain functions in a behaviorally-relevant system. We hope this inspires further research and thought into neurosteroid signaling in songbirds and other animals. PMID:19442685

  13. FoxP2 regulation during undirected singing in adult songbirds.

    PubMed

    Teramitsu, Ikuko; White, Stephanie A

    2006-07-12

    Learned vocal communication, including human speech, is a socially influenced behavior limited to certain animals. This ability requires auditory feedback during vocalization, which allows for on-line evaluation, to achieve the desired vocal output. To date, FOXP2 (forkhead box P2), a transcriptional repressor, is the only molecule directly linked to human speech. Identified FOXP2 mutations cause orofacial dyspraxia accompanied by abnormalities in corticostriatal circuitry controlling voluntary orofacial movements. These observations implicate FOXP2 in the developmental formation of neural circuits used in speech, but whether FOXP2 additionally plays an active role in mature circuitry was unknown. To address this question, we use a songbird, the zebra finch (Taeniopygia guttata), whose learned song and underlying circuitry are well characterized. We show that, when adult males sing, FoxP2 mRNA is acutely downregulated within area X, the specific region of the songbird striatum dedicated to song. Furthermore, we find downregulation in males that sing by themselves (undirected singers) but not in males that sing to females (directed singers). This FoxP2 downregulation cannot be a simple consequence of the motor act because birds sang in both directed and undirected contexts. Our data suggest that FoxP2 is important not only for the formation but also for the function of vocal control circuitry. Social context-dependent, acute changes in FoxP2 within the basal ganglia of adult songbirds also suggest, by analogy, that the core deficits of affected humans extend beyond development and beyond basic central motor control. PMID:16837586

  14. Measuring brain hemodynamic changes in a songbird: responses to hypercapnia measured with functional MRI and near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Vignal, C.; Boumans, T.; Montcel, B.; Ramstein, S.; Verhoye, M.; Van Audekerke, J.; Mathevon, N.; Van der Linden, A.; Mottin, S.

    2008-05-01

    Songbirds have been evolved into models of choice for the study of the cerebral underpinnings of vocal communication. Nevertheless, there is still a need for in vivo methods allowing the real-time monitoring of brain activity. Functional Magnetic Resonance Imaging (fMRI) has been applied in anesthetized intact songbirds. It relies on blood oxygen level-dependent (BOLD) contrast revealing hemodynamic changes. Non-invasive near-infrared spectroscopy (NIRS) is based on the weak absorption of near-infrared light by biological tissues. Time-resolved femtosecond white laser NIRS is a new probing method using real-time spectral measurements which give access to the local variation of absorbing chromophores such as hemoglobins. In this study, we test the efficiency of our time-resolved NIRS device in monitoring physiological hemodynamic brain responses in a songbird, the zebra finch (Taeniopygia guttata), using a hypercapnia event (7% inhaled CO2). The results are compared to those obtained using BOLD fMRI. The NIRS measurements clearly demonstrate that during hypercapnia the blood oxygen saturation level increases (increase in local concentration of oxyhemoglobin, decrease in deoxyhemoglobin concentration and total hemoglobin concentration). Our results provide the first correlation in songbirds of the variations in total hemoglobin and oxygen saturation level obtained from NIRS with local BOLD signal variations.

  15. ADNP: A major autism mutated gene is differentially distributed (age and gender) in the songbird brain.

    PubMed

    Kleiman, Gal Hacohen; Barnea, Anat; Gozes, Illana

    2015-10-01

    ADNP is a protein necessary for brain development, important for brain plasticity, cognitive and social functioning, characteristics that are all impaired in autism and in the Adnp(+/-) mouse model, in a sex-dependent manner. ADNP was originally discovered as a protein that is secreted from glial cells in response to vasoactive intestinal peptide (VIP). VIP is a major neuroprotective peptide in the CNS and PNS and was also associated with social recognition in rodents and aggression, pair-bonding and parental behaviors in birds. Comparative sequence alignment revealed high evolutionary conservation of ADNP in Chordata. Despite its importance in brain function, ADNP has never been studied in birds. Zebra finches (Taeniopygia guttata) are highly social songbirds that have a sexually dichotomous anatomical brain structure, with males demonstrating a developed song system, presenting a model to study behavior and potential sexually dependent fundamental differences. Here, using quantitative real time polymerase chain reaction (qRT-PCR), we discovered sexually dichotomous and age related differences in ADNP mRNA expression in three different regions of the song bird brain-cerebellum, cerebrum, and brain stem. Higher levels of ADNP mRNA were specifically found in young male compared to the female cerebrum, while aging caused a significant 2 and 3-fold decrease in the female and male cerebrum, respectively. Furthermore, a comparison between the three tested brain regions revealed unique sex-dependent ADNP mRNA distribution patterns, affected by aging. Future studies are aimed at deciphering the function of ADNP in birds, toward a better molecular understanding of sexual dichotomy in singing behavior in birds. PMID:25895853

  16. Estradiol differentially affects auditory recognition and learning according to photoperiodic state in the adult male songbird, European starling (Sturnus vulgaris)

    PubMed Central

    Knudsen, Daniel P.; Krause, Jesse S.; Wingfield, John C.; Gentner, Timothy Q.

    2013-01-01

    Changes in hormones can affect many types of learning in vertebrates. Adults experience fluctuations in a multitude of hormones over a temporal scale, from local, rapid action to more long-term, seasonal changes. Endocrine changes during development can affect behavioral outcomes in adulthood, but how learning is affected in adults by hormone fluctuations experienced during adulthood is less understood. Previous reports have implicated the sex steroid hormone estradiol (E2) in both male and female vertebrate cognitive functioning. Here, we examined the effects of E2 on auditory recognition and learning in male European starlings (Sturnus vulgaris). European starlings are photoperiodic, seasonally breeding songbirds that undergo different periods of reproductive activity according to annual changes in day length. We simulated these reproductive periods, specifically 1. photosensitivity, 2. photostimulation, and 3. photorefractoriness in captive birds by altering day length. During each period, we manipulated circulating E2 and examined multiple measures of learning. To manipulate circulating E2, we used subcutaneous implants containing either 17-β E2 and/or fadrozole (FAD), a highly specific aromatase inhibitor that suppresses E2 production in the body and the brain, and measured the latency for birds to learn and respond to short, male conspecific song segments (motifs). We report that photostimulated birds given E2 had higher response rates and responded with better accuracy than those given saline controls or FAD. Conversely, photosensitive, animals treated with E2 responded with less accuracy than those given FAD. These results demonstrate how circulating E2 and photoperiod can interact to shape auditory recognition and learning in adults, driving it in opposite directions in different states. PMID:24058881

  17. The Songbird Neurogenomics (SoNG) Initiative: Community-based tools and strategies for study of brain gene function and evolution

    PubMed Central

    Replogle, Kirstin; Arnold, Arthur P; Ball, Gregory F; Band, Mark; Bensch, Staffan; Brenowitz, Eliot A; Dong, Shu; Drnevich, Jenny; Ferris, Margaret; George, Julia M; Gong, George; Hasselquist, Dennis; Hernandez, Alvaro G; Kim, Ryan; Lewin, Harris A; Liu, Lei; Lovell, Peter V; Mello, Claudio V; Naurin, Sara; Rodriguez-Zas, Sandra; Thimmapuram, Jyothi; Wade, Juli; Clayton, David F

    2008-01-01

    Background Songbirds hold great promise for biomedical, environmental and evolutionary research. A complete draft sequence of the zebra finch genome is imminent, yet a need remains for application of genomic resources within a research community traditionally focused on ethology and neurobiological methods. In response, we developed a core set of genomic tools and a novel collaborative strategy to probe gene expression in diverse songbird species and natural contexts. Results We end-sequenced cDNAs from zebra finch brain and incorporated additional sequences from community sources into a database of 86,784 high quality reads. These assembled into 31,658 non-redundant contigs and singletons, which we annotated via BLAST search of chicken and human databases. The results are publicly available in the ESTIMA:Songbird database. We produced a spotted cDNA microarray with 20,160 addresses representing 17,214 non-redundant products of an estimated 11,500–15,000 genes, validating it by analysis of immediate-early gene (zenk) gene activation following song exposure and by demonstrating effective cross hybridization to genomic DNAs of other songbird species in the Passerida Parvorder. Our assembly was also used in the design of the "Lund-zfa" Affymetrix array representing ~22,000 non-redundant sequences. When the two arrays were hybridized to cDNAs from the same set of male and female zebra finch brain samples, both arrays detected a common set of regulated transcripts with a Pearson correlation coefficient of 0.895. To stimulate use of these resources by the songbird research community and to maintain consistent technical standards, we devised a "Community Collaboration" mechanism whereby individual birdsong researchers develop experiments and provide tissues, but a single individual in the community is responsible for all RNA extractions, labelling and microarray hybridizations. Conclusion Immediately, these results set the foundation for a coordinated set of 25 planned

  18. Two neural streams, one voice: pathways for theme and variation in the songbird brain.

    PubMed

    Bertram, R; Daou, A; Hyson, R L; Johnson, F; Wu, W

    2014-09-26

    Birdsong offers a unique model system to understand how a developing brain - once given a set of purely acoustic targets - teaches itself the vocal-tract gestures necessary to imitate those sounds. Like human infants, to juvenile male zebra finches (Taeniopygia guttata) falls the burden of initiating the vocal-motor learning of adult sounds. In both species, adult caregivers provide only a set of sounds to be imitated, with little or no information about the vocal-tract gestures used to produce the sounds. Here, we focus on the central control of birdsong and review the recent discovery that zebra finch song is under dual premotor control. Distinct forebrain pathways for structured (theme) and unstructured (variation) singing not only raise new questions about mechanisms of sensory-motor integration, but also provide a fascinating new research opportunity. A cortical locus for a motor memory of the learned song is now firmly established, meaning that anatomical, physiological, and computational approaches are poised to reveal the neural mechanisms used by the brain to compose the songs of birds. PMID:25106128

  19. Recovery of motor and cognitive function after cerebellar lesions in a songbird – role of estrogens

    PubMed Central

    Spence, Rory D.; Zhen, Yin; White, Stephanie; Schlinger, Barney A.; Day, Lainy B.

    2010-01-01

    In addition to its key role in complex motor function, the cerebellum is increasingly recognized to have a role in cognition. Songbirds are particularly good models for the investigation of motor and cognitive processes but little is known about the role of the songbird cerebellum in these processes. To explore cerebellar function in a songbird, we lesioned the cerebellum of adult female zebra finches and examined the effects on a spatial working memory task and on motor function during this task. There is evidence for steroid synthesis in the songbird brain and neurosteroids may have an impact on some forms of neural plasticity in adult songbirds. We therefore hypothesized that neurosteroids would affect motor and cognitive function after a cerebellar injury. We found that cerebellar lesions produced deficits in motor and cognitive aspects of a spatial task. In line with our prediction, birds in which estrogen synthesis was blocked had impaired performance in our spatial task compared with those that had estrogen synthesis blocked but estrogen replaced. There was no clear effect of estrogen replacement on motor function. We also found that lesions induced expression of the estrogen synthetic enzyme aromatase in reactive astrocytes and Bergmann glia around a cerebellar lesion. These data suggest that the cerebellum of songbirds mediates both motor and cognitive function and that estrogens may improve the recovery of cognitive aspects of cerebellar function after injury. PMID:19302157

  20. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

  1. Translating Birdsong: Songbirds as a model for basic and applied medical research

    PubMed Central

    2014-01-01

    Songbirds, long of interest to basic neuroscientists, have great potential as a model system for translational neuroscience. Songbirds learn their complex vocal behavior in a manner that exemplifies general processes of perceptual and motor skill learning, and more specifically resembles human speech learning. Song is subserved by circuitry that is specialized for vocal learning and production, but that has strong similarities to mammalian brain pathways. The combination of a highly quantifiable behavior and discrete neural substrates facilitates understanding links between brain and behavior, both normally and in disease. Here we highlight 1) behavioral and mechanistic parallels between birdsong and aspects of speech and social communication, including insights into mirror neurons, the function of auditory feedback, and genes underlying social communication disorders, and 2) contributions of songbirds to understanding cortical-basal ganglia circuit function and dysfunction, including the possibility of harnessing adult neurogenesis for brain repair. PMID:23750515

  2. GSK-3β Inhibition Affects Singing Behavior and Neurogenesis in Adult Songbirds.

    PubMed

    Aloni, Etay; Shapira, Moran; Eldar-Finkelman, Hagit; Barnea, Anat

    2015-01-01

    GSK-3 (glycogen synthase kinase-3) is a serine/threonine kinase which is a critical regulator in neuronal signaling, cognition, and behavior. We have previously shown that unlike other vertebrates that harbor both α and β GSK-3 genes, the α gene is missing in birds. Therefore, birds can be used as a new animal model to study the roles of GSK-3β in behavior and in regulating adult neurogenesis. In the present study, we inhibited GSK-3β in brains of adult male zebra finches (Taeniopygia guttata) and accordingly investigated how this inhibition affects behavior and cell proliferation. Our results show that GSK-3 inhibition: (1) affects specific aspects of singing behavior, which might be related to social interactions in birds, and (2) differentially affects cell proliferation in various parts of the ventricular zone. Taken together, our study demonstrates a role of GSK-3β in regulating singing behavior and neuronal proliferation in birds and highlights the importance of GSK-3β in modulating cognitive abilities as well as social behavior. PMID:26065821

  3. Postnatal growth rates covary weakly with embryonic development rates and do not explain adult mortality probability among songbirds on four continents.

    PubMed

    Martin, Thomas E; Oteyza, Juan C; Mitchell, Adam E; Potticary, Ahva L; Lloyd, Penn

    2015-03-01

    Growth and development rates may result from genetic programming of intrinsic processes that yield correlated rates between life stages. These intrinsic rates are thought to affect adult mortality probability and longevity. However, if proximate extrinsic factors (e.g., temperature, food) influence development rates differently between stages and yield low covariance between stages, then development rates may not explain adult mortality probability. We examined these issues based on study of 90 songbird species on four continents to capture the diverse life-history strategies observed across geographic space. The length of the embryonic period explained little variation (ca. 13%) in nestling periods and growth rates among species. This low covariance suggests that the relative importance of intrinsic and extrinsic influences on growth and development rates differs between stages. Consequently, nestling period durations and nestling growth rates were not related to annual adult mortality probability among diverse songbird species within or among sites. The absence of a clear effect of faster growth on adult mortality when examined in an evolutionary framework across species may indicate that species that evolve faster growth also evolve physiological mechanisms for ameliorating costs on adult mortality. Instead, adult mortality rates of species in the wild may be determined more strongly by extrinsic environmental causes. PMID:25674692

  4. Postnatal growth rates covary weakly with embryonic development rates and do not explain adult mortality probability among songbirds on four continents

    USGS Publications Warehouse

    Martin, Thomas E.; Oteyza, Juan C.; Mitchell, Adam E.; Potticary, Ahva L.; Lloyd, P.

    2016-01-01

    Growth and development rates may result from genetic programming of intrinsic processes that yield correlated rates between life stages. These intrinsic rates are thought to affect adult mortality probability and longevity. However, if proximate extrinsic factors (e.g., temperature, food) influence development rates differently between stages and yield low covariance between stages, then development rates may not explain adult mortality probability. We examined these issues based on study of 90 songbird species on four continents to capture the diverse life-history strategies observed across geographic space. The length of the embryonic period explained little variation (ca. 13%) in nestling periods and growth rates among species. This low covariance suggests that the relative importance of intrinsic and extrinsic influences on growth and development rates differs between stages. Consequently, nestling period durations and nestling growth rates were not related to annual adult mortality probability among diverse songbird species within or among sites. The absence of a clear effect of faster growth on adult mortality when examined in an evolutionary framework across species may indicate that species that evolve faster growth also evolve physiological mechanisms for ameliorating costs on adult mortality. Instead, adult mortality rates of species in the wild may be determined more strongly by extrinsic environmental causes.

  5. Brain cholinesterase inhibition in songbirds from pecan groves sprayed with phosaline and disulfoton

    USGS Publications Warehouse

    White, D.H.; Seginak, J.T.

    1990-01-01

    Disulfoton at 0.83 kg/ha caused moderate to severe brain cholinesterase (ChE) depression in 11 of 15 blue jays collected in pecan groves 6-7 hr after the application. Phosalone at 0.83 kg/ha to pecan groves caused only slight ChE inhibition in a few blue jays and red-bellied woodpeckers.

  6. Brain transcriptome sequencing and assembly of three songbird model systems for the study of social behavior

    PubMed Central

    Mukai, Motoko; Gonser, Rusty A.; Wingfield, John C.; London, Sarah E.; Tuttle, Elaina M.; Clayton, David F.

    2014-01-01

    Emberizid sparrows (emberizidae) have played a prominent role in the study of avian vocal communication and social behavior. We present here brain transcriptomes for three emberizid model systems, song sparrow Melospiza melodia, white-throated sparrow Zonotrichia albicollis, and Gambel’s white-crowned sparrow Zonotrichia leucophrys gambelii. Each of the assemblies covered fully or in part, over 89% of the previously annotated protein coding genes in the zebra finch Taeniopygia guttata, with 16,846, 15,805, and 16,646 unique BLAST hits in song, white-throated and white-crowned sparrows, respectively. As in previous studies, we find tissue of origin (auditory forebrain versus hypothalamus and whole brain) as an important determinant of overall expression profile. We also demonstrate the successful isolation of RNA and RNA-sequencing from post-mortem samples from building strikes and suggest that such an approach could be useful when traditional sampling opportunities are limited. These transcriptomes will be an important resource for the study of social behavior in birds and for data driven annotation of forthcoming whole genome sequences for these and other bird species. PMID:24883256

  7. Time-resolved and spectral-resolved optical imaging to study brain hemodynamics in songbirds

    NASA Astrophysics Data System (ADS)

    Mottin, Stéphane; Montcel, Bruno; Guillet de Chatellus, Hugues; Ramstein, Stéphane; Vignal, Clémentine; Mathevon, Nicolas

    2011-07-01

    Contrary to the intense debate about brain oxygen dynamics and its uncoupling in mammals, very little is known in birds. In zebra finches, picosecond optical tomography (POT) with a white laser and a streak camera can measure in vivo oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) concentration changes following physiological stimulation (familiar calls and songs). POT demonstrated sufficient sub-micromolar sensitivity to resolve the fast changes in hippocampus and auditory forebrain areas with 250 μm resolution. The time-course is composed of (i) an early 2s-long event with a significant decrease in Hb and HbO2, respectively -0.7 μMoles/L and -0.9 μMoles/L (ii) a subsequent increase in blood oxygen availability with a plateau of HbO2 (+0.3μMoles/L) and (iii) pronounced vasodilatation events immediately following the end of the stimulus. One of the findings of our work is the direct link between the blood oxygen level-dependent (BOLD) signals previously published in birds and our results. Furthermore, the early vasoconstriction event and post-stimulus ringing seem to be more pronounced in birds than in mammals. These results in bird, a tachymetabolic vertebrate with a long lifespan, can potentially yield new insights for example in brain aging.

  8. Localization of androgen receptors and estrogen receptors in the same cells of the songbird brain

    SciTech Connect

    Gahr, M. )

    1990-12-01

    Estrogens and androgens each have unique effects but act together for the neural differentiation and control of sexual behaviors in male vertebrates, such as the canary. The neuronal basis for these synergistic effects is elusive because the spatial relation between estrogen target cells and androgen target cells is unknown. This study localized estrogen receptor (ER)-containing cells by using immunocytochemistry and androgen receptor (AR)-containing cells by using autoradiography in the same sections of the male canary brain. Three cell types, those containing only ER, those containing only AR, and those containing both ER and AR, were found in tissue-specific frequencies. The midbrain nucleus intercollicularis exhibited the highest number of cells expressing both ER and AR, whereas ER and AR are expressed only in disjunctive cell populations in the forebrain nucleus hyperstriatalis ventrale, pars caudale. Synergistic effects of androgens and estrogens for the neural behavorial control could result from cells containing both ER and AR (intracellular) and from neural circuits containing ER and AR in different cells (intercellular).

  9. Auditory–vocal mirroring in songbirds

    PubMed Central

    Mooney, Richard

    2014-01-01

    Mirror neurons are theorized to serve as a neural substrate for spoken language in humans, but the existence and functions of auditory–vocal mirror neurons in the human brain remain largely matters of speculation. Songbirds resemble humans in their capacity for vocal learning and depend on their learned songs to facilitate courtship and individual recognition. Recent neurophysiological studies have detected putative auditory–vocal mirror neurons in a sensorimotor region of the songbird's brain that plays an important role in expressive and receptive aspects of vocal communication. This review discusses the auditory and motor-related properties of these cells, considers their potential role on song learning and communication in relation to classical studies of birdsong, and points to the circuit and developmental mechanisms that may give rise to auditory–vocal mirroring in the songbird's brain. PMID:24778375

  10. The genome of a songbird

    PubMed Central

    Warren, Wesley C.; Clayton, David F.; Ellegren, Hans; Arnold, Arthur P.; Hillier, LaDeana W.; Künstner, Axel; Searle, Steve; White, Simon; Vilella, Albert J.; Fairley, Susan; Heger, Andreas; Kong, Lesheng; Ponting, Chris P.; Jarvis, Erich D.; Mello, Claudio V.; Minx, Pat; Lovell, Peter; Velho, Tarciso A. F.; Ferris, Margaret; Balakrishnan, Christopher N.; Sinha, Saurabh; Blatti, Charles; London, Sarah E.; Li, Yun; Lin, Ya-Chi; George, Julia; Sweedler, Jonathan; Southey, Bruce; Gunaratne, Preethi; Watson, Michael; Nam, Kiwoong; Backström, Niclas; Smeds, Linnea; Nabholz, Benoit; Itoh, Yuichiro; Whitney, Osceola; Pfenning, Andreas R.; Howard, Jason; Völker, Martin; Skinner, Bejamin M.; Griffin, Darren K.; Ye, Liang; McLaren, William M.; Flicek, Paul; Quesada, Victor; Velasco, Gloria; Lopez-Otin, Carlos; Puente, Xose S.; Olender, Tsviya; Lancet, Doron; Smit, Arian F. A.; Hubley, Robert; Konkel, Miriam K.; Walker, Jerilyn A.; Batzer, Mark A.; Gu, Wanjun; Pollock, David D.; Chen, Lin; Cheng, Ze; Eichler, Evan E.; Stapley, Jessica; Slate, Jon; Ekblom, Robert; Birkhead, Tim; Burke, Terry; Burt, David; Scharff, Constance; Adam, Iris; Richard, Hugues; Sultan, Marc; Soldatov, Alexey; Lehrach, Hans; Edwards, Scott V.; Yang, Shiaw-Pyng; Li, XiaoChing; Graves, Tina; Fulton, Lucinda; Nelson, Joanne; Chinwalla, Asif; Hou, Shunfeng; Mardis, Elaine R.; Wilson, Richard K.

    2010-01-01

    The zebra finch is an important model organism in several fields1,2 with unique relevance to human neuroscience3,4. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken5—the only bird with a sequenced genome until now6. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes7. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour. PMID:20360741

  11. Pinealectomy abolishes circadian behavior and interferes with circadian clock gene oscillations in brain and liver but not retina in a migratory songbird.

    PubMed

    Trivedi, Amit Kumar; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

    2016-03-15

    In songbirds, the pineal gland is part of the multi-oscillatory circadian timing system, with participating component oscillators in the eyes and hypothalamus. This study investigated the role of the pineal gland in development of the nighttime migratory restlessness (Zugunruhe) and generation of circadian gene oscillations in the retina, brain and liver tissues in migratory redheaded buntings (Emberiza bruniceps). Pinealectomized (pinx) and sham-operated buntings entrained to short days (8h light: 16h darkness, 8L:16D) were sequentially exposed for 10days each to stimulatory long days (13L: 11D) and constant dim light (LLdim; a condition that tested circadian rhythm persistence). Whereas activity-rest pattern was monitored continuously, the mRNA expressions of clock genes (bmal1, clock, npas2, per2, cry1, rorα, reverα) were measured in the retina, hypothalamus, telencephalon, optic tectum and liver tissues at circadian times, CT, 1, 6, 13, 17 and 21 (CT 0, activity onset) on day 11 of the LLdim. The absence of the pineal gland did not affect the development of long-day induced Zugunruhe but caused decay of the circadian rhythm in Zugunruhe as well as the clock gene oscillations in the hypothalamus, but not in the retina. Further, there were variable effects of pinealectomy in the peripheral brain and liver tissue circadian gene oscillations, notably the persistence of per 2 and cry1 (optic tectum), rorα (telencephalon) and npas2 (liver) mRNA oscillations in pinx birds. We suggest the pineal gland dependence of the generation of circadian gene oscillations in the hypothalamus, not retina, and peripheral brain and liver tissues in migratory redheaded buntings. PMID:26801391

  12. Temporal pattern processing in songbirds.

    PubMed

    Comins, Jordan A; Gentner, Timothy Q

    2014-10-01

    Understanding how the brain perceives, organizes and uses patterned information is directly related to the neurobiology of language. Given the present limitations, such knowledge at the scale of neurons, neural circuits and neural populations can only come from non-human models, focusing on shared capacities that are relevant to language processing. Here we review recent advances in the behavioral and neural basis of temporal pattern processing of natural auditory communication signals in songbirds, focusing on European starlings. We suggest a general inhibitory circuit for contextual modulation that can act to control sensory representations based on patterning rules. PMID:25201176

  13. Genomics analysis of potassium channel genes in songbirds reveals molecular specializations of brain circuits for the maintenance and production of learned vocalizations

    PubMed Central

    2013-01-01

    Background A fundamental question in molecular neurobiology is how genes that determine basic neuronal properties shape the functional organization of brain circuits underlying complex learned behaviors. Given the growing availability of complete vertebrate genomes, comparative genomics represents a promising approach to address this question. Here we used genomics and molecular approaches to study how ion channel genes influence the properties of the brain circuitry that regulates birdsong, a learned vocal behavior with important similarities to human speech acquisition. We focused on potassium (K-)Channels, which are major determinants of neuronal cell excitability. Starting with the human gene set of K-Channels, we used cross-species mRNA/protein alignments, and syntenic analysis to define the full complement of orthologs, paralogs, allelic variants, as well as novel loci not previously predicted in the genome of zebra finch (Taeniopygia guttata). We also compared protein coding domains in chicken and zebra finch orthologs to identify genes under positive selective pressure, and those that contained lineage-specific insertions/deletions in functional domains. Finally, we conducted comprehensive in situ hybridizations to determine the extent of brain expression, and identify K-Channel gene enrichments in nuclei of the avian song system. Results We identified 107 K-Channel finch genes, including 6 novel genes common to non-mammalian vertebrate lineages. Twenty human genes are absent in songbirds, birds, or sauropsids, or unique to mammals, suggesting K-Channel properties may be lineage-specific. We also identified specific family members with insertions/deletions and/or high dN/dS ratios compared to chicken, a non-vocal learner. In situ hybridization revealed that while most K-Channel genes are broadly expressed in the brain, a subset is selectively expressed in song nuclei, representing molecular specializations of the vocal circuitry. Conclusions Together

  14. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  15. Early experience shapes vocal neural coding and perception in songbirds

    PubMed Central

    Woolley, Sarah M. N.

    2012-01-01

    Songbirds, like humans, are highly accomplished vocal learners. The many parallels between speech and birdsong and conserved features of mammalian and avian auditory systems have led to the emergence of the songbird as a model system for studying the perceptual mechanisms of vocal communication. Laboratory research on songbirds allows the careful control of early life experience and high-resolution analysis of brain function during vocal learning, production and perception. Here, I review what songbird studies have revealed about the role of early experience in the development of vocal behavior, auditory perception and the processing of learned vocalizations by auditory neurons. The findings of these studies suggest general principles for how exposure to vocalizations during development and into adulthood influences the perception of learned vocal signals. PMID:22711657

  16. Brain size and limits to adult neurogenesis.

    PubMed

    Paredes, Mercedes F; Sorrells, Shawn F; Garcia-Verdugo, Jose M; Alvarez-Buylla, Arturo

    2016-02-15

    The walls of the cerebral ventricles in the developing embryo harbor the primary neural stem cells from which most neurons and glia derive. In many vertebrates, neurogenesis continues postnatally and into adulthood in this region. Adult neurogenesis at the ventricle has been most extensively studied in organisms with small brains, such as reptiles, birds, and rodents. In reptiles and birds, these progenitor cells give rise to young neurons that migrate into many regions of the forebrain. Neurogenesis in adult rodents is also relatively widespread along the lateral ventricles, but migration is largely restricted to the rostral migratory stream into the olfactory bulb. Recent work indicates that the wall of the lateral ventricle is highly regionalized, with progenitor cells giving rise to different types of neurons depending on their location. In species with larger brains, young neurons born in these spatially specified domains become dramatically separated from potential final destinations. Here we hypothesize that the increase in size and topographical complexity (e.g., intervening white matter tracts) in larger brains may severely limit the long-term contribution of new neurons born close to, or in, the ventricular wall. We compare the process of adult neuronal birth, migration, and integration across species with different brain sizes, and discuss how early regional specification of progenitor cells may interact with brain size and affect where and when new neurons are added. PMID:26417888

  17. Growth and splitting of neural sequences in songbird vocal development.

    PubMed

    Okubo, Tatsuo S; Mackevicius, Emily L; Payne, Hannah L; Lynch, Galen F; Fee, Michale S

    2015-12-17

    Neural sequences are a fundamental feature of brain dynamics underlying diverse behaviours, but the mechanisms by which they develop during learning remain unknown. Songbirds learn vocalizations composed of syllables; in adult birds, each syllable is produced by a different sequence of action potential bursts in the premotor cortical area HVC. Here we carried out recordings of large populations of HVC neurons in singing juvenile birds throughout learning to examine the emergence of neural sequences. Early in vocal development, HVC neurons begin producing rhythmic bursts, temporally locked to a 'prototype' syllable. Different neurons are active at different latencies relative to syllable onset to form a continuous sequence. Through development, as new syllables emerge from the prototype syllable, initially highly overlapping burst sequences become increasingly distinct. We propose a mechanistic model in which multiple neural sequences can emerge from the growth and splitting of a common precursor sequence. PMID:26618871

  18. Growth and splitting of neural sequences in songbird vocal development

    PubMed Central

    Okubo, Tatsuo S.; Mackevicius, Emily L.; Payne, Hannah L.; Lynch, Galen F.; Fee, Michale S.

    2015-01-01

    Neural sequences are a fundamental feature of brain dynamics underlying diverse behaviors, but the mechanisms by which they develop during learning remain unknown. Songbirds learn vocalizations composed of syllables; in adult birds, each syllable is produced by a different sequence of action potential bursts in the premotor cortical area HVC. Here we carried out recordings of large populations of HVC neurons in singing juvenile birds throughout learning to examine the emergence of neural sequences. Early in vocal development, HVC neurons begin producing rhythmic bursts, temporally locked to a ‘prototype’ syllable. Different neurons are active at different latencies relative to syllable onset to form a continuous sequence. Through development, as new syllables emerge from the prototype syllable, initially highly overlapping burst sequences become increasingly distinct. We propose a mechanistic model in which multiple neural sequences can emerge from the growth and splitting of a common precursor sequence. PMID:26618871

  19. Shared neural substrates for song discrimination in parental and parasitic songbirds.

    PubMed

    Louder, Matthew I M; Voss, Henning U; Manna, Thomas J; Carryl, Sophia S; London, Sarah E; Balakrishnan, Christopher N; Hauber, Mark E

    2016-05-27

    In many social animals, early exposure to conspecific stimuli is critical for the development of accurate species recognition. Obligate brood parasitic songbirds, however, forego parental care and young are raised by heterospecific hosts in the absence of conspecific stimuli. Having evolved from non-parasitic, parental ancestors, how brood parasites recognize their own species remains unclear. In parental songbirds (e.g. zebra finch Taeniopygia guttata), the primary and secondary auditory forebrain areas are known to be critical in the differential processing of conspecific vs. heterospecific songs. Here we demonstrate that the same auditory brain regions underlie song discrimination in adult brood parasitic pin-tailed whydahs (Vidua macroura), a close relative of the zebra finch lineage. Similar to zebra finches, whydahs showed stronger behavioral responses during conspecific vs. heterospecific song and tone pips as well as increased neural responses within the auditory forebrain, as measured by both functional magnetic resonance imaging (fMRI) and immediate early gene (IEG) expression. Given parallel behavioral and neuroanatomical patterns of song discrimination, our results suggest that the evolutionary transition to brood parasitism from parental songbirds likely involved an "evolutionary tinkering" of existing proximate mechanisms, rather than the wholesale reworking of the neural substrates of species recognition. PMID:27095589

  20. Exploring Heterozygosity-Survival Correlations in a Wild Songbird Population: Contrasting Effects between Juvenile and Adult Stages

    PubMed Central

    Canal, David; Serrano, David; Potti, Jaime

    2014-01-01

    The relationship between genetic diversity and fitness, a major issue in evolutionary and conservation biology, is expected to be stronger in traits affected by many loci and those directly influencing fitness. Here we explore the influence of heterozygosity measured at 15 neutral markers on individual survival, one of the most important parameters determining individual fitness. We followed individual survival up to recruitment and during subsequent adult life of 863 fledgling pied flycatchers born in two consecutive breeding seasons. Mark-recapture analyses showed that individual heterozygosity did not influence juvenile or adult survival. In contrast, the genetic relatedness of parents was negatively associated with the offspring’s survival during the adult life, but this effect was not apparent in the juvenile (from fledgling to recruitment) stage. Stochastic factors experienced during the first year of life in this long-distance migratory species may have swamped a relationship between heterozygosity and survival up to recruitment. PMID:25122217

  1. Development of Auditory-Vocal Perceptual Skills in Songbirds

    PubMed Central

    Miller-Sims, Vanessa C.; Bottjer, Sarah W.

    2012-01-01

    Songbirds are one of the few groups of animals that learn the sounds used for vocal communication during development. Like humans, songbirds memorize vocal sounds based on auditory experience with vocalizations of adult “tutors”, and then use auditory feedback of self-produced vocalizations to gradually match their motor output to the memory of tutor sounds. In humans, investigations of early vocal learning have focused mainly on perceptual skills of infants, whereas studies of songbirds have focused on measures of vocal production. In order to fully exploit songbirds as a model for human speech, understand the neural basis of learned vocal behavior, and investigate links between vocal perception and production, studies of songbirds must examine both behavioral measures of perception and neural measures of discrimination during development. Here we used behavioral and electrophysiological assays of the ability of songbirds to distinguish vocal calls of varying frequencies at different stages of vocal learning. The results show that neural tuning in auditory cortex mirrors behavioral improvements in the ability to make perceptual distinctions of vocal calls as birds are engaged in vocal learning. Thus, separate measures of neural discrimination and behavioral perception yielded highly similar trends during the course of vocal development. The timing of this improvement in the ability to distinguish vocal sounds correlates with our previous work showing substantial refinement of axonal connectivity in cortico-basal ganglia pathways necessary for vocal learning. PMID:23285011

  2. Anatomically discrete sex differences and enhancement by testosterone of cell proliferation in the telencephalic ventricle zone of the adult canary brain

    PubMed Central

    Barker, Jennifer M.; Ball, Gregory F.; Balthazart, Jacques

    2013-01-01

    Previous work in songbirds has suggested that testosterone increases neuronal recruitment and survival in HVC but does not affect neuronal proliferation in the ventricular zone and that males and females have similar rates of proliferation except at discrete locations. Many of these conclusions are however based on limited data or were inferred indirectly. Here we specifically tested the effects of testosterone on cellular proliferation in the ventricular zone of both male and female adult canaries. We implanted adult birds of both sexes with testosterone or empty implants for one week and injected them with BrdU. One day later, we collected their brains and quantified BrdU-positive cells in the ventricular zone (VZ) at different rostro-caudal levels of the brain, ranging from the level where the song nucleus Area X occurs through the caudal extent of HVC. Proliferation in the dorsal part of the VZ was low and unaffected by sex or testosterone treatment. In the ventral part of the VZ, females had more proliferating cells than males, but only at rostral levels, near Area X. Also in the ventral part of the VZ, testosterone increased proliferation in birds of both sexes, but only in the mid- to caudal-VZ, caudal to the level of Area X, around the septum and HVC. We thus demonstrate here that there is both an effect of testosterone and possibly a more subtle effect of sex on cellular proliferation in the adult songbird brain, and that these effects are specific to different levels of the brain. PMID:24211440

  3. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    ERIC Educational Resources Information Center

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  4. Evaluation of Reference Genes for Quantitative Real-Time PCR in Songbirds

    PubMed Central

    Zinzow-Kramer, Wendy M.; Horton, Brent M.; Maney, Donna L.

    2014-01-01

    Quantitative real-time PCR (qPCR) is becoming a popular tool for the quantification of gene expression in the brain and endocrine tissues of songbirds. Accurate analysis of qPCR data relies on the selection of appropriate reference genes for normalization, yet few papers on songbirds contain evidence of reference gene validation. Here, we evaluated the expression of ten potential reference genes (18S, ACTB, GAPDH, HMBS, HPRT, PPIA, RPL4, RPL32, TFRC, and UBC) in brain, pituitary, ovary, and testis in two species of songbird: zebra finch and white-throated sparrow. We used two algorithms, geNorm and NormFinder, to assess the stability of these reference genes in our samples. We found that the suitability of some of the most popular reference genes for target gene normalization in mammals, such as 18S, depended highly on tissue type. Thus, they are not the best choices for brain and gonad in these songbirds. In contrast, we identified alternative genes, such as HPRT, RPL4 and PPIA, that were highly stable in brain, pituitary, and gonad in these species. Our results suggest that the validation of reference genes in mammals does not necessarily extrapolate to other taxonomic groups. For researchers wishing to identify and evaluate suitable reference genes for qPCR songbirds, our results should serve as a starting point and should help increase the power and utility of songbird models in behavioral neuroendocrinology. PMID:24780145

  5. Guidelines for Better Communication with Brain Impaired Adults

    MedlinePlus

    ... A You are here Home Guidelines for Better Communication with Brain Impaired Adults Printer-friendly version Communicating ... easy solutions, following some basic guidelines should ease communication, and lower levels of stress both for you ...

  6. Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species

    PubMed Central

    Chen, Qianqian; Heston, Jonathan B.; Burkett, Zachary D.; White, Stephanie A.

    2013-01-01

    SUMMARY Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song. PMID:24006346

  7. Memory and Brain Volume in Adults Prenatally Exposed to Alcohol

    ERIC Educational Resources Information Center

    Coles, Claire D.; Goldstein, Felicia C.; Lynch, Mary Ellen; Chen, Xiangchuan; Kable, Julie A.; Johnson, Katrina C.; Hu, Xiaoping

    2011-01-01

    The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n = 26; Alcohol-related Neurodevelopmental Disorder, n = 36; and Dysmorphic, n = 30) were imaged using structural MRI with brain volume calculated for…

  8. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  9. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  10. New Nerve Cells for the Adult Brain.

    ERIC Educational Resources Information Center

    Kempermann, Gerd; Gage, Fred H.

    1999-01-01

    Contrary to dogma, the human brain does produce new nerve cells in adulthood. The mature human brain spawns neurons routinely in the hippocampus, an area important to memory and learning. This research can make it possible to ease any number of disorders involving neurological damage and death. (CCM)

  11. Substance use and brain reward mechanisms in older adults.

    PubMed

    Snyder, Marsha; Platt, Lois

    2013-07-01

    Substance use among older adults is on the rise, with statistics indicating this to be a growing health problem. Brain changes in the reward center of the brain that naturally occur with aging are offered as one source of these statistics. Aging is generally associated with increased prevalence of chronic disease, disability, and death, and therefore a public health goal for older adults is to maintain health, independence, and function. Psychiatric-mental health nurses are uniquely positioned to assist older adults in achievement of these goals through health assessment and promotion. The use of client-centered counseling approaches that recognize the older adult's developmental need for autonomy and choice in decision making have been shown to be effective in increasing motivation in this adult population. PMID:23758223

  12. Histomorphological Phenotyping of the Adult Mouse Brain.

    PubMed

    Mikhaleva, Anna; Kannan, Meghna; Wagner, Christel; Yalcin, Binnaz

    2016-01-01

    This article describes a series of standard operating procedures for morphological phenotyping of the mouse brain using basic histology. Many histological studies of the mouse brain use qualitative approaches based on what the human eye can detect. Consequently, some phenotypic information may be missed. Here we describe a quantitative approach for the assessment of brain morphology that is simple and robust. A total of 78 measurements are made throughout the brain at specific and well-defined regions, including the cortex, the hippocampus, and the cerebellum. Experimental design and timeline considerations, including strain background effects, the importance of sectioning quality, measurement variability, and efforts to correct human errors are discussed. © 2016 by John Wiley & Sons, Inc. PMID:27584555

  13. Adult mouse brain gene expression patterns bear an embryologic imprint

    PubMed Central

    Zapala, Matthew A.; Hovatta, Iiris; Ellison, Julie A.; Wodicka, Lisa; Del Rio, Jo A.; Tennant, Richard; Tynan, Wendy; Broide, Ron S.; Helton, Rob; Stoveken, Barbara S.; Winrow, Christopher; Lockhart, Daniel J.; Reilly, John F.; Young, Warren G.; Bloom, Floyd E.; Lockhart, David J.; Barlow, Carrolee

    2005-01-01

    The current model to explain the organization of the mammalian nervous system is based on studies of anatomy, embryology, and evolution. To further investigate the molecular organization of the adult mammalian brain, we have built a gene expression-based brain map. We measured gene expression patterns for 24 neural tissues covering the mouse central nervous system and found, surprisingly, that the adult brain bears a transcriptional “imprint” consistent with both embryological origins and classic evolutionary relationships. Embryonic cellular position along the anterior–posterior axis of the neural tube was shown to be closely associated with, and possibly a determinant of, the gene expression patterns in adult structures. We also observed a significant number of embryonic patterning and homeobox genes with region-specific expression in the adult nervous system. The relationships between global expression patterns for different anatomical regions and the nature of the observed region-specific genes suggest that the adult brain retains a degree of overall gene expression established during embryogenesis that is important for regional specificity and the functional relationships between regions in the adult. The complete collection of extensively annotated gene expression data along with data mining and visualization tools have been made available on a publicly accessible web site (www.barlow-lockhart-brainmapnimhgrant.org). PMID:16002470

  14. The effects of vitamin D on brain development and adult brain function.

    PubMed

    Kesby, James P; Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

    2011-12-01

    A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine. PMID:21664231

  15. A brain sexual dimorphism controlled by adult circulating androgens.

    PubMed

    Cooke, B M; Tabibnia, G; Breedlove, S M

    1999-06-22

    Reports of structural differences between the brains of men and women, heterosexual and homosexual men, and male-to-female transsexuals and other men have been offered as evidence that the behavioral differences between these groups are likely caused by differences in the early development of the brain. However, a possible confounding variable is the concentration of circulating hormones seen in these groups in adulthood. Evaluation of this possibility hinges on the extent to which circulating hormones can alter the size of mammalian brain regions as revealed by Nissl stains. We now report a sexual dimorphism in the volume of a brain nucleus in rats that can be completely accounted for by adult sex differences in circulating androgen. The posterodorsal nucleus of the medial amygdala (MePD) has a greater volume in male rats than in females, but adult castration of males causes the volume to shrink to female values within four weeks, whereas androgen treatment of adult females for that period enlarges the MePD to levels equivalent to normal males. This report demonstrates that adult hormone manipulations can completely reverse a sexual dimorphism in brain regional volume in a mammalian species. The sex difference and androgen responsiveness of MePD volume is reflected in the soma size of neurons there. PMID:10377450

  16. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  17. Inflammation is detrimental for neurogenesis in adult brain

    NASA Astrophysics Data System (ADS)

    Ekdahl, Christine T.; Claasen, Jan-Hendrik; Bonde, Sara; Kokaia, Zaal; Lindvall, Olle

    2003-11-01

    New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.

  18. [Chemotherapy for brain tumors in adult patients].

    PubMed

    Weller, M

    2008-02-01

    Chemotherapy has become a third major treatment option for patients with brain tumors, in addition to surgery and radiotherapy. The role of chemotherapy in the treatment of gliomas is no longer limited to recurrent disease. Temozolomide has become the standard of care in newly diagnosed glioblastoma. Several ongoing trials seek to define the role of chemotherapy in the primary care of other gliomas. Some of these studies are no longer only based on histological diagnoses, but take into consideration molecular markers such as MGMT promoter methylation and loss of genetic material on chromosomal arms 1p and 19q. Outside such clinical trials chemotherapy is used in addition to radiotherapy, e.g., in anaplastic astrocytoma, medulloblastoma or germ cell tumors, or as an alternative to radiotherapy, e.g., in anaplastic oligodendroglial tumors or low-grade gliomas. In contrast, there is no established role for chemotherapy in other tumors such as ependymomas, meningiomas or neurinomas. Primary cerebral lymphomas are probably the only brain tumors which can be cured by chemotherapy alone and only by chemotherapy. The chemotherapy of brain metastases follows the recommendations for the respective primary tumors. Further, strategies of combined radiochemotherapy using mainly temozolomide or topotecan are currently explored. Leptomeningeal metastases are treated by radiotherapy or systemic or intrathecal chemotherapy depending on their pattern of growth. PMID:18253773

  19. Bilateral Brain Regions Associated with Naming in Older Adults

    ERIC Educational Resources Information Center

    Obler, Loraine K.; Rykhlevskaia, Elena; Schnyer, David; Clark-Cotton, Manuella R.; Spiro, Avron, III; Hyun, JungMoon; Kim, Dae-Shik; Goral, Mira; Albert, Martin L.

    2010-01-01

    To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall,…

  20. Pedophilic brain potential responses to adult erotic stimuli.

    PubMed

    Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul

    2016-02-01

    Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. PMID:26683083

  1. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  2. A New Mechanism of Sound Generation in Songbirds

    NASA Astrophysics Data System (ADS)

    Goller, Franz; Larsen, Ole N.

    1997-12-01

    Our current understanding of the sound-generating mechanism in the songbird vocal organ, the syrinx, is based on indirect evidence and theoretical treatments. The classical avian model of sound production postulates that the medial tympaniform membranes (MTM) are the principal sound generators. We tested the role of the MTM in sound generation and studied the songbird syrinx more directly by filming it endoscopically. After we surgically incapacitated the MTM as a vibratory source, zebra finches and cardinals were not only able to vocalize, but sang nearly normal song. This result shows clearly that the MTM are not the principal sound source. The endoscopic images of the intact songbird syrinx during spontaneous and brain stimulation-induced vocalizations illustrate the dynamics of syringeal reconfiguration before phonation and suggest a different model for sound production. Phonation is initiated by rostrad movement and stretching of the syrinx. At the same time, the syrinx is closed through movement of two soft tissue masses, the medial and lateral labia, into the bronchial lumen. Sound production always is accompanied by vibratory motions of both labia, indicating that these vibrations may be the sound source. However, because of the low temporal resolution of the imaging system, the frequency and phase of labial vibrations could not be assessed in relation to that of the generated sound. Nevertheless, in contrast to the previous model, these observations show that both labia contribute to aperture control and strongly suggest that they play an important role as principal sound generators.

  3. Life Satisfaction in Adult Survivors of Childhood Brain Tumors

    PubMed Central

    Crom, Deborah B.; Li, Zhenghong; Brinkman, Tara M.; Hudson, Melissa M.; Armstrong, Gregory T.; Neglia, Joseph; Ness, Kirsten K.

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, life-long deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors’ physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggests some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population–based matched controls. Chi-square tests, t-tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors’ general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population. PMID:25027187

  4. A revised dosimetric model of the adult head and brain

    SciTech Connect

    Bouchet, L.G.; Bolch, W.E.; Weber, D.A.

    1996-06-01

    During the last decade, new radiopharmaceutical have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head. Brain and head models developed in the past have been only simplistic representations of this anatomic region. For example, the brain within the phantom of MIRD Pamphlet No. 5 Revised is modeled simply as a single ellipsoid of tissue With no differentiation of its internal structures. To address this need, the MIRD Committee established a Task Group in 1992 to construct a more detailed brain model to include the cerebral cortex, the white matter, the cerebellum, the thalamus, the caudate nucleus, the lentiform nucleus, the cerebral spinal fluid, the lateral ventricles, and the third ventricle. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. This model has been incorporated into the radiation transport code EGS4 so as to calculate photon and electron absorbed fractions in the energy range 10 keV to 4 MeV for each of thirteen sources in the brain. Furthermore, explicit positron transport have been considered, separating the contribution by the positron itself and its associated annihilations photons. No differences are found between the electron and positron absorbed fractions; however, for initial energies of positrons greater than {approximately}0.5 MeV, significant differences are found between absorbed fractions from explicit transport of annihilation photons and those from an assumed uniform distribution of 0.511-MeV photons. Subsequently, S values were calculated for a variety of beta-particle and positron emitters brain imaging agents. Moreover, pediatric head and brain dosimetric models are currently being developed based on this adult head model.

  5. The adult human brain harbors multipotent perivascular mesenchymal stem cells.

    PubMed

    Paul, Gesine; Özen, Ilknur; Christophersen, Nicolaj S; Reinbothe, Thomas; Bengzon, Johan; Visse, Edward; Jansson, Katarina; Dannaeus, Karin; Henriques-Oliveira, Catarina; Roybon, Laurent; Anisimov, Sergey V; Renström, Erik; Svensson, Mikael; Haegerstrand, Anders; Brundin, Patrik

    2012-01-01

    Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain. PMID:22523602

  6. Immunological regulation of neurogenic niches in the adult brain

    PubMed Central

    Gonzalez-Perez, Oscar; Gutierrez-Fernandez, Fernando; Lopez-Virgen, Veronica; Collas-Aguilar, Jorge; Quinones-Hinojosa, Alfredo; Garcia-Verdugo, Jose M.

    2012-01-01

    In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular (SVZ) and subgranular (SGZ) zones are the main neurogenic regions in adult brain. Therein, it resides a subpopulation of astrocytes that act as neural stem cells. Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of neural stem cells. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor-alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of neural stem cells and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult neural stem cells under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells. PMID:22986164

  7. Isolation and culture of neurospheres from the adult newt brain.

    PubMed

    Hameed, Liyakath Ali Shahul; Simon, András

    2015-01-01

    Neural stem cells (NSCs) give rise to neurons in the adult brain and are possible targets in regenerative therapies. In vitro cultures of NSCs as neurospheres have been established from cells isolated from diverse species. Newts are exceptional regenerators among vertebrates. These animals are able to efficiently replace neurons following ablation of those by activation and subsequent differentiation of NSCs. Here we describe the method for isolating and culturing of NSCs from the newt brain both during self-renewing and differentiating conditions. Newt NSC culture provides a useful tool for functional studies of NSC fate with the potential of resulting in novel regenerative strategies. PMID:25740488

  8. Effects of pesticides on songbird productivity in conjunction with pecan cultivation in southern Georgia: A multiple-exposure experimental design

    USGS Publications Warehouse

    Patnode, K.A.; White, D.H.

    1991-01-01

    A prototypic experimental design was used to assess sublethal effects of multiple and varied organophosphates and carbamates on reproduction in birds. The design allowed for classification of pesticide exposure according to toxicity of applied compounds and type and frequency of applications. Daily survival rates (DSRs) of nests, eggs, and nestlings were determined for northern mockingbirds (Mimus polyglottos), brown thrashers (Toxostoma rufum), and northern cardinals (Cardinalis cardinalis) nesting along edges of pecan orchards and row crops in southern Georgia [USA]. Egg and nestling DSRs for all species combined varied inversely (P 0.05) among three exposure levels. Brain cholinesterase activities were age-dependent and substantiated adult, but not nestling, exposure. Results suggest that increasing exposure to pesticides may reduce songbird productivity.

  9. Electrophysiological recording in the brain of intact adult zebrafish.

    PubMed

    Johnston, Lindsey; Ball, Rebecca E; Acuff, Seth; Gaudet, John; Sornborger, Andrew; Lauderdale, James D

    2013-01-01

    Previously, electrophysiological studies in adult zebrafish have been limited to slice preparations or to eye cup preparations and electrorentinogram recordings. This paper describes how an adult zebrafish can be immobilized, intubated, and used for in vivo electrophysiological experiments, allowing recording of neural activity. Immobilization of the adult requires a mechanism to deliver dissolved oxygen to the gills in lieu of buccal and opercular movement. With our technique, animals are immobilized and perfused with habitat water to fulfill this requirement. A craniotomy is performed under tricaine methanesulfonate (MS-222; tricaine) anesthesia to provide access to the brain. The primary electrode is then positioned within the craniotomy window to record extracellular brain activity. Through the use of a multitube perfusion system, a variety of pharmacological compounds can be administered to the adult fish and any alterations in the neural activity can be observed. The methodology not only allows for observations to be made regarding changes in neurological activity, but it also allows for comparisons to be made between larval and adult zebrafish. This gives researchers the ability to identify the alterations in neurological activity due to the introduction of various compounds at different life stages. PMID:24300281

  10. Exploration and visualization of connectivity in the adult mouse brain.

    PubMed

    Feng, David; Lau, Chris; Ng, Lydia; Li, Yang; Kuan, Leonard; Sunkin, Susan M; Dang, Chinh; Hawrylycz, Michael

    2015-02-01

    The Allen Mouse Brain Connectivity Atlas is a mesoscale whole brain axonal projection atlas of the C57Bl/6J mouse brain. All data were aligned to a common template in 3D space to generate a comprehensive and quantitative database of inter-areal and cell-type-specific projections. A suite of computational tools were developed to search and visualize the projection labeling experiments, available at http://connectivity.brain-map.org. We present three use cases illustrating how these publicly-available tools can be used to perform analyses of long range brain region connectivity. The use cases make extensive use of advanced visualization tools integrated with the atlas including projection density histograms, 3D computed anterograde and retrograde projection paths, and multi-specimen projection composites. These tools offer convenient access to detailed axonal projection information in the adult mouse brain and the ability to perform data analysis and visualization of projection fields and neuroanatomy in an integrated manner. PMID:25637033

  11. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  12. Brain Network Activity in Monolingual and Bilingual Older Adults

    PubMed Central

    Grady, Cheryl L.; Luk, Gigi; Craik, Fergus I.M.; Bialystok, Ellen

    2016-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life. PMID:25445783

  13. An anatomic gene expression atlas of the adult mouse brain.

    PubMed

    Ng, Lydia; Bernard, Amy; Lau, Chris; Overly, Caroline C; Dong, Hong-Wei; Kuan, Chihchau; Pathak, Sayan; Sunkin, Susan M; Dang, Chinh; Bohland, Jason W; Bokil, Hemant; Mitra, Partha P; Puelles, Luis; Hohmann, John; Anderson, David J; Lein, Ed S; Jones, Allan R; Hawrylycz, Michael

    2009-03-01

    Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of genes in the Allen Brain Atlas (ABA). The AGEA includes three discovery tools for examining neuroanatomical relationships and boundaries: (1) three-dimensional expression-based correlation maps, (2) a hierarchical transcriptome-based parcellation of the brain and (3) a facility to retrieve from the ABA specific genes showing enriched expression in local correlated domains. The utility of this atlas is illustrated by analysis of genetic organization in the thalamus, striatum and cerebral cortex. The AGEA is a publicly accessible online computational tool integrated with the ABA (http://mouse.brain-map.org/agea). PMID:19219037

  14. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N.; Post, Jeremy; Woods, Amina S.; Hoffer, Barry J.; Wang, Yun; Harvey, Brandon K.

    2009-01-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.—Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats. PMID:19218497

  15. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation. PMID:22300952

  16. Gonadotropin releasing hormone (GnRH) and gonadotropin inhibitory hormone (GnIH) in the songbird hippocampus: regional and sex differences in adult zebra finches.

    PubMed

    McGuire, Nicolette; Ferris, Jennifer K; Arckens, Lutgarde; Bentley, George E; Soma, Kiran K

    2013-08-01

    Hypothalamic gonadotropin releasing hormone (GnRH) and gonadotropin inhibitory hormone (GnIH) are vital to reproduction in all vertebrates. These neuropeptides are also present outside of the hypothalamus, but the roles of extra-hypothalamic GnRH and GnIH remain enigmatic and widely underappreciated. We used immunohistochemistry and PCR to examine whether multiple forms of GnRH (chicken GnRH-I (GnRH1), chicken GnRH-II (GnRH2) and lamprey GnRH-III (GnRH4)) and GnIH are present in the hippocampus (Hp) of adult zebra finches (Taeniopygia guttata). Using immunohistochemistry, we provide evidence that GnRH1, GnRH2 and GnRH4 are present in hippocampal cell bodies and/or fibers and that GnIH is present in hippocampal fibers only. There are regional differences in hippocampal GnRH immunoreactivity, and these vary across the different forms of GnRH. There are also sex differences in hippocampal GnRH immunoreactivity, with generally more GnRH1 and GnRH2 in the female Hp. In addition, we used PCR to examine the presence of GnRH1 mRNA and GnIH mRNA in micropunches of Hp. PCR and subsequent product sequencing demonstrated the presence of GnRH1 mRNA and the absence of GnIH mRNA in the Hp, consistent with the pattern of immunohistochemical results. To our knowledge, this is the first study in any species to systematically examine multiple forms of GnRH in the Hp or to quantify sex or regional differences in hippocampal GnRH. Moreover, this is the first demonstration of GnIH in the avian Hp. These data shed light on an important issue: the sites of action and possible functions of GnRH and GnIH outside of the HPG axis. PMID:23727031

  17. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    SciTech Connect

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-15

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  18. Neuroimaging in adult penetrating brain injury: a guide for radiographers.

    PubMed

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings. PMID:26229677

  19. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  20. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  1. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  2. Roles for Oestrogen Receptor β in Adult Brain Function

    PubMed Central

    Handa, R. J.; Ogawa, S.; Wang, J. M.; Herbison, A. E.

    2012-01-01

    Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ERβ located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety-like behaviour; (ii) ERβ expressed in gonadotrophin-releasing hormone neurones contributing to oestrogen negative-feedback control of gonadotrophin secretion; (iii) ERβ controlling the offset of lordosis behaviour; (iv) ERβ suppressing aggressive behaviour in males; (v) ERβ modulating responses to social stimuli; and (vi) ERβ in controlling adult neurogenesis. This review highlights two major themes; first, ERβ and ERα are usually tightly inter-related in the oestradiol-dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ERα-dependent mechanisms, modulatory roles for ERβ also exist. Second, the roles of ERα and ERβ within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ERα to enhance, and ERβ to suppress, anxiety-like and aggressive behaviours. Splice variants such as ERβ2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ERβ in mediating the many effects of oestradiol upon adult brain function. PMID:21851428

  3. Neurogenesis in the adult brain: implications for Alzheimer's disease.

    PubMed

    Galvan, Veronica; Bredesen, Dale E

    2007-10-01

    The function of neurogenesis in the adult brain is still unknown. Interventions such as environmental enrichment and exercise impinge on neurogenesis, suggesting that the process is regulated by experience. Conversely, a role for neurogenesis in learning has been proposed through 'cellular plasticity', a process akin to synaptic plasticity but operating at the network level. Although neurogenesis is stimulated by acute injury, and possibly by neurodegenerative processes such as Alzheimer's disease (AD), it does not suffice to restore function. While the role and direction of change in the neurogenic response at different stages of AD is still a matter of debate, it is possible that a deficit in neurogenesis may contribute to AD pathogenesis since at least one of the two regions ostensibly neurogenic in the adult human brain (the subgranular zone of the dentage gyrus and the ventriculo-olfactory neurogenic system) support high-level functions affected in early AD (associative memory and olfaction respectively). The age of onset and the rate of progression of sporadic forms of AD are highly variable. Sporadic AD may have a component of insufficient neurogenic replacement or insufficient neurogenic stimulation that is correlated with traits of personal history; the rate of neurogenesis and the survival of replicating progenitors is strongly modified by behavioral interventions known to impinge on the rate of neurogenesis and the probability of survival of newly born neurons--exercise, enriched experience, and learning. This view is consistent with epidemiological data suggesting that higher education and increased participation in intellectual, social and physical aspects of daily life are associated with slower cognitive decline in healthy elderly ("cognitive reserve") and may reduce the risk of AD. Although neurogenesis can be modulated exogenously by growth factors, stimulation of neurogenesis as a mean to treat neurodegeneration is still for the most part

  4. Variations on a theme: songbirds, variability, and sensorimotor error correction

    PubMed Central

    Kuebrich, Benjamin; Sober, Samuel

    2014-01-01

    Songbirds provide a powerful animal model for investigating how the brain uses sensory feedback to correct behavioral errors. Here, we review a recent study in which we used online manipulations of auditory feedback to quantify the relationship between sensory error size, motor variability, and vocal plasticity. We found that although inducing small auditory errors evoked relatively large compensatory changes in behavior, as error size increased the magnitude of error correction declined. Furthermore, when we induced large errors such that auditory signals no longer overlapped with the baseline distribution of feedback, the magnitude of error correction approached zero. This pattern suggests a simple and robust strategy for the brain to maintain the accuracy of learned behaviors by evaluating sensory signals relative to the previously experienced distribution of feedback. Drawing from recent studies of auditory neurophysiology and song discrimination, we then speculate as to the mechanistic underpinnings of the results obtained in our behavioral experiments. Finally, we review how our own and other studies exploit the strengths of the songbird system, both in the specific context of vocal systems and more generally as a model of the neural control of complex behavior. PMID:25305664

  5. Variations on a theme: Songbirds, variability, and sensorimotor error correction.

    PubMed

    Kuebrich, B D; Sober, S J

    2015-06-18

    Songbirds provide a powerful animal model for investigating how the brain uses sensory feedback to correct behavioral errors. Here, we review a recent study in which we used online manipulations of auditory feedback to quantify the relationship between sensory error size, motor variability, and vocal plasticity. We found that although inducing small auditory errors evoked relatively large compensatory changes in behavior, as error size increased the magnitude of error correction declined. Furthermore, when we induced large errors such that auditory signals no longer overlapped with the baseline distribution of feedback, the magnitude of error correction approached zero. This pattern suggests a simple and robust strategy for the brain to maintain the accuracy of learned behaviors by evaluating sensory signals relative to the previously experienced distribution of feedback. Drawing from recent studies of auditory neurophysiology and song discrimination, we then speculate as to the mechanistic underpinnings of the results obtained in our behavioral experiments. Finally, we review how our own and other studies exploit the strengths of the songbird system, both in the specific context of vocal systems and more generally as a model of the neural control of complex behavior. PMID:25305664

  6. Toxic exposure of songbirds to lead in the Southeast Missouri Lead Mining District

    USGS Publications Warehouse

    Beyer, W. Nelson; Franson, J. Christian; French, John B.; May, Thomas; Rattner, Barnett A.; Shearn-Bochsler, Valerie I.; Warner, Sarah E.; Weber, John; Mosby, David

    2013-01-01

    Mining and smelting in the Southeast Missouri Lead Mining District has caused widespread contamination of soils with lead (Pb) and other metals. Soils from three study sites sampled in the district contained from approximately 1,000–3,200 mg Pb/kg. Analyses of earthworms [33–4,600 mg Pb/kg dry weight (dw)] collected in the district showed likely high Pb exposure of songbirds preying on soil organisms. Mean tissue Pb concentrations in songbirds collected from the contaminated sites were greater (p < 0.05) than those in songbirds from reference sites by factors of 8 in blood, 13 in liver, and 23 in kidney. Ranges of Pb concentrations in livers (mg Pb/kg dw) were as follows: northern cardinal (Cardinalis cardinalis) = 0.11–3.0 (reference) and 1.3–30 (contaminated) and American robin (Turdus migratorius) = 0.43–8.5 (reference) and 7.6–72 (contaminated). Of 34 adult and juvenile songbirds collected from contaminated sites, 11 (32 %) had hepatic Pb concentrations that were consistent with adverse physiological effects, 3 (9 %) with systemic toxic effects, and 4 (12 %) with life-threatening toxic effects. Acid-fast renal intranuclear inclusion bodies, which are indicative of Pb poisoning, were detected in kidneys of two robins that had the greatest renal Pb concentrations (952 and 1,030 mg/kg dw). Mean activity of the enzyme delta-aminolevulinic acid dehydratase (ALAD) in red blood cells, a well-established bioindicator of Pb poisoning in birds, was decreased by 58–82 % in songbirds from the mining sites. We conclude that habitats within the mining district with soil Pb concentrations of ≥1,000 mg Pb/kg are contaminated to the extent that they are exposing ground-feeding songbirds to toxic concentrations of Pb.

  7. Toxic exposure of songbirds to lead in the Southeast Missouri Lead Mining District.

    PubMed

    Beyer, W Nelson; Franson, J Christian; French, John B; May, Thomas; Rattner, Barnett A; Shearn-Bochsler, Valerie I; Warner, Sarah E; Weber, John; Mosby, David

    2013-10-01

    Mining and smelting in the Southeast Missouri Lead Mining District has caused widespread contamination of soils with lead (Pb) and other metals. Soils from three study sites sampled in the district contained from approximately 1,000-3,200 mg Pb/kg. Analyses of earthworms [33-4,600 mg Pb/kg dry weight (dw)] collected in the district showed likely high Pb exposure of songbirds preying on soil organisms. Mean tissue Pb concentrations in songbirds collected from the contaminated sites were greater (p < 0.05) than those in songbirds from reference sites by factors of 8 in blood, 13 in liver, and 23 in kidney. Ranges of Pb concentrations in livers (mg Pb/kg dw) were as follows: northern cardinal (Cardinalis cardinalis) = 0.11-3.0 (reference) and 1.3-30 (contaminated) and American robin (Turdus migratorius) = 0.43-8.5 (reference) and 7.6-72 (contaminated). Of 34 adult and juvenile songbirds collected from contaminated sites, 11 (32%) had hepatic Pb concentrations that were consistent with adverse physiological effects, 3 (9%) with systemic toxic effects, and 4 (12%) with life-threatening toxic effects. Acid-fast renal intranuclear inclusion bodies, which are indicative of Pb poisoning, were detected in kidneys of two robins that had the greatest renal Pb concentrations (952 and 1,030 mg/kg dw). Mean activity of the enzyme delta-aminolevulinic acid dehydratase (ALAD) in red blood cells, a well-established bioindicator of Pb poisoning in birds, was decreased by 58-82% in songbirds from the mining sites. We conclude that habitats within the mining district with soil Pb concentrations of ≥1,000 mg Pb/kg are contaminated to the extent that they are exposing ground-feeding songbirds to toxic concentrations of Pb. PMID:23771631

  8. Evaluation of an automatic brain segmentation method developed for neonates on adult MR brain images

    NASA Astrophysics Data System (ADS)

    Moeskops, Pim; Viergever, Max A.; Benders, Manon J. N. L.; Išgum, Ivana

    2015-03-01

    Automatic brain tissue segmentation is of clinical relevance in images acquired at all ages. The literature presents a clear distinction between methods developed for MR images of infants, and methods developed for images of adults. The aim of this work is to evaluate a method developed for neonatal images in the segmentation of adult images. The evaluated method employs supervised voxel classification in subsequent stages, exploiting spatial and intensity information. Evaluation was performed using images available within the MRBrainS13 challenge. The obtained average Dice coefficients were 85.77% for grey matter, 88.66% for white matter, 81.08% for cerebrospinal fluid, 95.65% for cerebrum, and 96.92% for intracranial cavity, currently resulting in the best overall ranking. The possibility of applying the same method to neonatal as well as adult images can be of great value in cross-sectional studies that include a wide age range.

  9. Diminished adult neurogenesis in the marmoset brain precedes old age

    PubMed Central

    Leuner, Benedetta; Kozorovitskiy, Yevgenia; Gross, Charles G.; Gould, Elizabeth

    2007-01-01

    With aging there is a decline in the number of newly generated neurons in the dentate gyrus of the hippocampus. In rodents and tree shrews, this age-related decrease in neurogenesis is evident long before the animals become aged. No previous studies have investigated whether primates exhibit a similar decline in hippocampal neurogenesis with aging. To investigate this possibility, young to middle aged adult common marmosets (Callithrix jacchus) were injected with BrdU and perfused 3 weeks later. The number of newly generated cells in the subgranular zone/granule cell layer of the dentate gyrus was significantly lower in older animals and decreased linearly with age. A similar age-related decline in new cells was observed in the subventricular zone but not in the hilar region of the dentate gyrus. These data demonstrate that a substantial decrease in neurogenesis occurs before the onset of old age in the adult marmoset brain, suggesting the possibility that similar alterations occur in the human brain. PMID:17940008

  10. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    PubMed

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-10-01

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization. PMID:26384869

  11. Axonal injury and regeneration in the adult brain of Drosophila

    PubMed Central

    Ayaz, Derya; Leyssen, Maarten; Koch, Marta; Yan, Jiekun; Srahna, Mohammed; Sheeba, Vasu; Fogle, Keri J.; Holmes, Todd C.; Hassan, Bassem A.

    2009-01-01

    Drosophila melanogaster is a leading genetic model system in nervous system development and disease research. Using the power of fly genetics in traumatic axonal injury research will significantly speed up the characterization of molecular processes that control axonal regeneration in the Central Nervous System (CNS). We developed a versatile and physiologically robust preparation for the long-term culture of the whole Drosophila brain. We use this method to develop a novel Drosophila model for CNS axonal injury and regeneration. We first show that, similar to mammalian CNS axons, injured adult wild type fly CNS axons fail to regenerate, whereas adult-specific enhancement of Protein Kinase A activity increases the regenerative capacity of lesioned neurons. Combined, these observations suggest conservation of neuronal regeneration mechanisms following injury. We next exploit this model to explore pathways that induce robust regeneration and find that adult-specific activation of JNK signalling is sufficient for de novo CNS axonal regeneration after injury, including the growth of new axons past the lesion site and into the normal target area. PMID:18524906

  12. Stroke Incidence Following Traumatic Brain Injury in Older Adults

    PubMed Central

    Albrecht, Jennifer S.; Liu, Xinggang; Smith, Gordon S.; Baumgarten, Mona; Rattinger, Gail B.; Gambert, Steven R.; Langenberg, Patricia; Zuckerman, Ilene H.

    2015-01-01

    Objective Following traumatic brain injury (TBI), older adults are at increased risk of hemorrhagic and thromboembolic events, but it is unclear whether the increased risk continues after hospital discharge. We estimated incidence rates of hemorrhagic and ischemic stroke following hospital discharge for TBI among adults ≥65 and compared them with pre-TBI rates. Participants 16,936 Medicare beneficiaries aged ≥65 with a diagnosis of TBI in any position on an inpatient claim between 6/1/2006 and 12/31/2009 who survived to hospital discharge. Design Retrospective analysis of a random 5% sample of Medicare claims data Main Measures Hemorrhagic stroke was defined as ICD-9 codes 430.xx-432.xx. Ischemic stroke was defined as ICD-9 codes 433.xx-435.xx, 437.0x, and 437.1x. Results There was a six-fold increase in the rate of hemorrhagic stroke following TBI compared to the pre-TBI period (adjusted Rate Ratio (RR) 6.5; 95% Confidence Interval (CI) 5.3, 7.8), controlling for age and sex. A smaller increase in the rate of ischemic stroke was observed (adjusted RR 1.3; 95% CI 1.2, 1.4). Conclusion Future studies should investigate causes of increased stroke risk post-TBI as well as effective treatments to reduce stroke risk and improve outcomes post-TBI among older adults. PMID:24816156

  13. Resting-State Brain Activity in Adult Males Who Stutter

    PubMed Central

    Zhu, Chaozhe; Wang, Liang; Yan, Qian; Lin, Chunlan; Yu, Chunshui

    2012-01-01

    Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them. PMID:22276215

  14. Songbirds as sentinels of mercury in terrestrial habitats of eastern North America

    USGS Publications Warehouse

    Jackson, Allyson K.; Evers, David C.; Adams, Evan M.; Cristol, Daniel A.; Eagles-Smith, Collin A.; Edmonds, Samuel T.; Gray, Carrie E.; Hoskins, Bart; Lane, Oksana P.; Sauer, Amy; Tear, Timothy

    2015-01-01

    Mercury (Hg) is a globally distributed environmental contaminant with a variety of deleterious effects in fish, wildlife, and humans. Breeding songbirds may be useful sentinels for Hg across diverse habitats because they can be effectively sampled, have well-defined and small territories, and can integrate pollutant exposure over time and space. We analyzed blood total Hg concentrations from 8,446 individuals of 102 species of songbirds, sampled on their breeding territories across 161 sites in eastern North America [geometric mean Hg concentration = 0.25 μg/g wet weight (ww), range <0.01–14.60 μg/g ww]. Our records span an important time period—the decade leading up to implementation of the USEPA Mercury and Air Toxics Standards, which will reduce Hg emissions from coal-fired power plants by over 90 %. Mixed-effects modeling indicated that habitat, foraging guild, and age were important predictors of blood Hg concentrations across species and sites. Blood Hg concentrations in adult invertebrate-eating songbirds were consistently higher in wetland habitats (freshwater or estuarine) than upland forests. Generally, adults exhibited higher blood Hg concentrations than juveniles within each habitat type. We used model results to examine species-specific differences in blood Hg concentrations during this time period, identifying potential Hg sentinels in each region and habitat type. Our results present the most comprehensive assessment of blood Hg concentrations in eastern songbirds to date, and thereby provide a valuable framework for designing and evaluating risk assessment schemes using sentinel songbird species in the time after implementation of the new atmospheric Hg standards.

  15. Neural Correlates of Auditory Processing, Learning and Memory Formation in Songbirds

    NASA Astrophysics Data System (ADS)

    Pinaud, R.; Terleph, T. A.; Wynne, R. D.; Tremere, L. A.

    Songbirds have emerged as powerful experimental models for the study of auditory processing of complex natural communication signals. Intact hearing is necessary for several behaviors in developing and adult animals including vocal learning, territorial defense, mate selection and individual recognition. These behaviors are thought to require the processing, discrimination and memorization of songs. Although much is known about the brain circuits that participate in sensorimotor (auditory-vocal) integration, especially the ``song-control" system, less is known about the anatomical and functional organization of central auditory pathways. Here we discuss findings associated with a telencephalic auditory area known as the caudomedial nidopallium (NCM). NCM has attracted significant interest as it exhibits functional properties that may support higher order auditory functions such as stimulus discrimination and the formation of auditory memories. NCM neurons are vigorously dr iven by auditory stimuli. Interestingly, these responses are selective to conspecific, relative to heterospecific songs and artificial stimuli. In addition, forms of experience-dependent plasticity occur in NCM and are song-specific. Finally, recent experiments employing high-throughput quantitative proteomics suggest that complex protein regulatory pathways are engaged in NCM as a result of auditory experience. These molecular cascades are likely central to experience-associated plasticity of NCM circuitry and may be part of a network of calcium-driven molecular events that support the formation of auditory memory traces.

  16. Mechanisms underlying the social enhancement of vocal learning in songbirds.

    PubMed

    Chen, Yining; Matheson, Laura E; Sakata, Jon T

    2016-06-14

    Social processes profoundly influence speech and language acquisition. Despite the importance of social influences, little is known about how social interactions modulate vocal learning. Like humans, songbirds learn their vocalizations during development, and they provide an excellent opportunity to reveal mechanisms of social influences on vocal learning. Using yoked experimental designs, we demonstrate that social interactions with adult tutors for as little as 1 d significantly enhanced vocal learning. Social influences on attention to song seemed central to the social enhancement of learning because socially tutored birds were more attentive to the tutor's songs than passively tutored birds, and because variation in attentiveness and in the social modulation of attention significantly predicted variation in vocal learning. Attention to song was influenced by both the nature and amount of tutor song: Pupils paid more attention to songs that tutors directed at them and to tutors that produced fewer songs. Tutors altered their song structure when directing songs at pupils in a manner that resembled how humans alter their vocalizations when speaking to infants, that was distinct from how tutors changed their songs when singing to females, and that could influence attention and learning. Furthermore, social interactions that rapidly enhanced learning increased the activity of noradrenergic and dopaminergic midbrain neurons. These data highlight striking parallels between humans and songbirds in the social modulation of vocal learning and suggest that social influences on attention and midbrain circuitry could represent shared mechanisms underlying the social modulation of vocal learning. PMID:27247385

  17. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    PubMed Central

    Oliva, Carolina A.; Vargas, Jessica Y.; Inestrosa, Nibaldo C.

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer’s disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts. PMID:24348327

  18. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain.

    PubMed

    Creeley, Catherine E; Wozniak, David F; Nardi, Anthony; Farber, Nuri B; Olney, John W

    2008-02-01

    The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer's disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine's neurotoxic potential has not been investigated. In the present study, we determined that a dose of memantine (20mg/kg, i.p.), considered to be in the therapeutic (neuroprotective) range for rats, causes a mild neurotoxic reaction in the adult rat brain. Co-administration of memantine (20 or 30 mg/kg) with donepezil (2.5-10mg/kg) markedly potentiated this neurotoxic reaction, causing neuronal injury at lower doses of memantine, and causing the toxic reaction to become disseminated and lethal to neurons throughout many brain regions. These findings raise questions about using this drug combination in AD, especially in the absence of evidence that the combination is beneficial, or that either drug arrests or reverses the disease process. PMID:17112636

  19. Exploratory case-control study of brain tumors in adults

    SciTech Connect

    Burch, J.D.; Craib, K.J.; Choi, B.C.; Miller, A.B.; Risch, H.A.; Howe, G.R.

    1987-04-01

    An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.

  20. Traumatic brain injury: endocrine consequences in children and adults.

    PubMed

    Richmond, Erick; Rogol, Alan D

    2014-02-01

    Traumatic brain injury (TBI) is a common cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioral, psychological and social defects. Recent data suggest that pituitary hormone deficiency is not infrequent among TBI survivors; the prevalence of reported hypopituitarism following TBI varies widely among published studies. The most common cause of TBI is motor vehicle accidents, including pedestrian-car and bicycle car encounters, falls, child abuse, violence and sports injuries. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90 %. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Endocrine dysfunction after TBI in children and adolescents is common. Adolescence is a time of growth, freedom and adjustment, consequently TBI is also common in this group. Sports-related TBI is an important public health concern, but many cases are unrecognized and unreported. Sports that are associated with an increased risk of TBI include those involving contact and/or collisions such as boxing, football, soccer, ice hockey, rugby, and the martial arts, as well as high velocity sports such as cycling, motor racing, equestrian sports, skiing and roller skating. The aim of this paper is to summarize the best evidence of TBI as a cause of pituitary deficiency in children and adults. PMID:24030696

  1. Adult neurogenesis in the decapod crustacean brain: A hematopoietic connection?

    PubMed Central

    Beltz, Barbara S.; Zhang, Yi; Benton, Jeanne L.; Sandeman, David C.

    2011-01-01

    New neurons are produced and integrated into circuits in the adult brains of many organisms, including crustaceans. In some crustacean species, the 1st- generation neuronal precursors reside in a niche exhibiting characteristics analogous to mammalian neurogenic niches. However, unlike mammalian niches where several generations of neuronal precursors coexist, the lineage of precursor cells in crayfish is spatially separated allowing the influence of environmental and endogenous regulators on specific generations in the neuronal precursor lineage to be defined. Experiments also demonstrate that the 1st-generation neuronal precursors in the crayfish Procambarus clarkii are not self-renewing. A source external to the neurogenic niche must therefore provide cells that replenish the 1st-generation precursor pool, because although these cells divide and produce a continuous efflux of 2nd-generation cells from the niche, the population of 1st-generation niche precursors is not diminished with growth and aging. In vitro studies show that cells extracted from the hemolymph, but not other tissues, are attracted to and incorporated into the neurogenic niche, a phenomenon that appears to involve serotonergic mechanisms. We propose that in crayfish, the hematopoietic system may be a source of cells that replenish the niche cell pool. These and other studies reviewed here establish decapod crustaceans as model systems in which the processes underlying adult neurogenesis, such as stem cell origins and transformation, can be readily explored. Studies in diverse species where adult neurogenesis occurs will result in a broader understanding of fundamental mechanisms and how evolutionary processes may have shaped the vertebrate/mammalian condition. PMID:21929622

  2. The microtubule-associated protein doublecortin is broadly expressed in the telencephalon of adult canaries

    PubMed Central

    Boseret, Géraldine; Ball, Gregory F.; Balthazart, Jacques

    2007-01-01

    The protein Doublecortin (DCX) is expressed in post-mitotic migrating and differentiating neurons in the developing vertebrate brain and, as a part of the microtubule machinery, is required for neuronal migration. DCX expression is generally maximal during embryonic and early post-natal life but decreases markedly and almost disappears in older animals in parallel with the major decrease or cessation of neurogenesis. In several seasonally breeding songbird species such as canaries, the volume of several song control nuclei in the brain varies seasonally such that the largest nuclei are observed in the late spring and early summer. This variation is based on changes in cell size, dendritic branching, and, in nucleus HVC, on the incorporation of neurons newly born in adulthood. Because songbirds maintain an active neurogenesis and neuronal incorporation in their telencephalon throughout their lives, we investigated here the distribution of DCX-immunoreactive (ir) structures in the brain of adult male canaries. Densely stained DCX-ir cells were found exclusively in parts of the telencephalon that are known to incorporate new neurons in adulthood, in particular the nidopallium. Within this brain region, the boundaries of the song control nucleus HVC could be clearly distinguished from surrounding structures by a higher density of DCX-ir structures. In most telencephalic areas, about two thirds of these cells displayed a uni- or bipolar fusiform morphology suggesting they were migrating neurons. The rest of the DCX-ir cells in the telencephalon were larger and had a round multipolar morphology. No such staining was found in the rest of the brain. The broad expression of DCX specifically in adult brain structures that exhibit the characteristic of active incorporation of new neurons suggests that DCX plays a key role in the migration of new neurons in the brain of adult songbirds as it presumably does during ontogeny. PMID:17367992

  3. Construction of brain atlases based on a multi-center MRI dataset of 2020 Chinese adults.

    PubMed

    Liang, Peipeng; Shi, Lin; Chen, Nan; Luo, Yishan; Wang, Xing; Liu, Kai; Mok, Vincent C T; Chu, Winnie C W; Wang, Defeng; Li, Kuncheng

    2015-01-01

    Despite the known morphological differences (e.g., brain shape and size) in the brains of populations of different origins (e.g., age and race), the Chinese brain atlas is less studied. In the current study, we developed a statistical brain atlas based on a multi-center high quality magnetic resonance imaging (MRI) dataset of 2020 Chinese adults (18-76 years old). We constructed 12 Chinese brain atlas from the age 20 year to the age 75 at a 5 years interval. New Chinese brain standard space, coordinates, and brain area labels were further defined. The new Chinese brain atlas was validated in brain registration and segmentation. It was found that, as contrast to the MNI152 template, the proposed Chinese atlas showed higher accuracy in hippocampus segmentation and relatively smaller shape deformations during registration. These results indicate that a population-specific time varying brain atlas may be more appropriate for studies involving Chinese populations. PMID:26678304

  4. The Origin of Time in the Songbird Motor Pathway

    NASA Astrophysics Data System (ADS)

    Long, Michael

    2010-03-01

    Many complex behaviors, like speech or music, have a hierarchical organization with structure on many timescales. How does the brain control the timing and ordering of behavioral sequences? Do different circuits control different timescales of the behavior? To begin answering these questions, we use temperature to manipulate the biophysical dynamics in different regions of the songbird forebrain involved in song production. We found that cooling premotor nucleus HVC (high vocal center) uniformly slows song speed by up to 40% while only slightly altering the acoustic structure, whereas cooling downstream motor nucleus RA (robust nucleus of the arcopallium) has no observable effect on song timing, despite a marked affect of RA spiking activity. To better understand the circuit mechanisms of precise premotor timing, we perform intracellular recordings in RA-projecting HVC neurons during singing. Our observations suggest highly ordered dynamics within HVC which are consistent with a synfire-like neuronal architecture.

  5. GABA regulates synaptic integration of newly generated neurons in the adult brain

    NASA Astrophysics Data System (ADS)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  6. Effect of exposure to diazinon on adult rat's brain.

    PubMed

    Rashedinia, Marzieh; Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Lari, Parisa; Razavi, Bibi Marjan; Abnous, Khalil

    2016-04-01

    Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain. PMID:24217015

  7. Encoding of mechanical nociception differs in the adult and infant brain

    PubMed Central

    Fabrizi, Lorenzo; Verriotis, Madeleine; Williams, Gemma; Lee, Amy; Meek, Judith; Olhede, Sofia; Fitzgerald, Maria

    2016-01-01

    Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0–19 days (n = 18, clinically required) and adults aged 23–48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2–4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain. PMID:27345331

  8. Encoding of mechanical nociception differs in the adult and infant brain.

    PubMed

    Fabrizi, Lorenzo; Verriotis, Madeleine; Williams, Gemma; Lee, Amy; Meek, Judith; Olhede, Sofia; Fitzgerald, Maria

    2016-01-01

    Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0-19 days (n = 18, clinically required) and adults aged 23-48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2-4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain. PMID:27345331

  9. A model to predict breeding-season productivity for multibrooded songbirds

    USGS Publications Warehouse

    Powell, L.A.; Conroy, M.J.; Krementz, D.G.; Lang, J.D.

    1999-01-01

    Breeding-season productivity (the per capita number of offspring surviving to the end of the breeding season) is seldom estimated for multibrooded songbirds because of cost and logistical constraints. However, this parameter is critical for predictions of population growth rates and comparisons of seasonal productivity across geographic or temporal scales. We constructed a dynamic, stochastic, individual-based model of breeding-season productivity using demographic data from Wood Thrushes (Hylocichla mustelina) in central Georgia from 1993 to 1996. The model predicts breeding-season productivity as a function of adult survival, juvenile survival, nesting success, season length, renesting interval, and juvenile-care intervals. The model predicted that seasonal fecundity (number of fledglings produced) was 3.04, but only 2.04 juveniles per female survived to the end of the breeding season. Sensitivity analyses showed that differences in renesting interval, nesting success, fledglings per successful nest, and adult and juvenile survival caused variation in breeding-season productivity. Contrary to commonly held notions, season length and fledg-ling-care interval length did not cause variation in breeding-season productivity. This modeling exercise emphasizes the need for demographic data for songbird species, and we encourage biologists to use similar models to evaluate productivity in songbird populations.

  10. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  11. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases.

    PubMed

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors. PMID:27375363

  12. LIFE HISTORY. Age-related mortality explains life history strategies of tropical and temperate songbirds.

    PubMed

    Martin, Thomas E

    2015-08-28

    Life history theory attempts to explain why species differ in offspring number and quality, growth rate, and parental effort. I show that unappreciated interactions of these traits in response to age-related mortality risk challenge traditional perspectives and explain life history evolution in songbirds. Counter to a long-standing paradigm, tropical songbirds grow at similar overall rates to temperate species but grow wings relatively faster. These growth tactics are favored by predation risk, both in and after leaving the nest, and are facilitated by greater provisioning of individual offspring by parents. Increased provisioning of individual offspring depends on partitioning effort among fewer young because of constraints on effort from adult and nest mortality. These growth and provisioning responses to mortality risk finally explain the conundrum of small clutch sizes of tropical birds. PMID:26315435

  13. Physical performance limitations among adult survivors of childhood brain tumors

    PubMed Central

    Ness, Kirsten K.; Morris, E. Brannon; Nolan, Vikki G.; Howell, Carrie R.; Gilchrist, Laura S.; Stovall, Marilyn; Cox, Cheryl L.; Klosky, James L.; Gajjar, Amar; Neglia, Joseph P.

    2013-01-01

    Background Young adult survivors of childhood brain tumors (BT) may have late-effects that compromise physical performance and everyday task participation. Objective To evaluate muscle strength, fitness, physical performance, and task participation among adult survivors of childhood BT. Design/Method In-home evaluations and interviews were conducted for 156 participants (54% male). Results on measures of muscle strength, fitness, physical performance, and participation were compared between survivors and population-group members with chi-squared statistics and two-sample t-tests. Associations between late effects and physical performance, and physical performance and participation, were evaluated in regression models. Results BT survivors were a median age of 22 (18–58), and 14.7 (6.5–45.9) years from diagnosis. Survivors had lower estimates of grip strength (Female: 24.7±9.2 vs. 31.5±5.8, Male: 39.0±12.2 vs. 53.0±10.1 kilograms), knee extension strength (Female: 246.6±95.5 vs. 331.5±5.8, Male: 304.7±116.4 vs. 466.6±92.1 Newtons) and peak oxygen uptake (Female: 25.1±8.8 vs. 31.3±5.1, Male: 24.6±9.5 vs. 33.2±3.4 milliliters/kilogram/minute) than population-group members. Physical performance was lower among survivors and associated with not living independently (OR=5.0, 95% CI=2.0–12.2) and not attending college (OR=2.3, 95% CI 1.2–4.4). Conclusion Muscle strength and fitness values among BT survivors are similar to those among persons 60+ years, and are associated with physical performance limitations. Physical performance limitations are associated with poor outcomes in home and school environments. These data indicate an opportunity for interventions targeted at improving long-term physical function in this survivor population. PMID:20564409

  14. Recovery from Mild Traumatic Brain Injury in Previously Healthy Adults.

    PubMed

    Losoi, Heidi; Silverberg, Noah D; Wäljas, Minna; Turunen, Senni; Rosti-Otajärvi, Eija; Helminen, Mika; Luoto, Teemu M; Julkunen, Juhani; Öhman, Juha; Iverson, Grant L

    2016-04-15

    This prospective longitudinal study reports recovery from mild traumatic brain injury (MTBI) across multiple domains in a carefully selected consecutive sample of 74 previously healthy adults. The patients with MTBI and 40 orthopedic controls (i.e., ankle injuries) completed assessments at 1, 6, and 12 months after injury. Outcome measures included cognition, post-concussion symptoms, depression, traumatic stress, quality of life, satisfaction with life, resilience, and return to work. Patients with MTBI reported more post-concussion symptoms and fatigue than the controls at the beginning of recovery, but by 6 months after injury, did not differ as a group from nonhead injury trauma controls on cognition, fatigue, or mental health, and by 12 months, their level of post-concussion symptoms and quality of life was similar to that of controls. Almost all (96%) patients with MTBI returned to work/normal activities (RTW) within the follow-up of 1 year. A subgroup of those with MTBIs and controls reported mild post-concussion-like symptoms at 1 year. A large percentage of the subgroup who had persistent symptoms had a modifiable psychological risk factor at 1 month (i.e., depression, traumatic stress, and/or low resilience), and at 6 months, they had greater post-concussion symptoms, fatigue, insomnia, traumatic stress, and depression, and worse quality of life. All of the control subjects who had mild post-concussion-like symptoms at 12 months also had a mental health problem (i.e., depression, traumatic stress, or both). This illustrates the importance of providing evidence-supported treatment and rehabilitation services early in the recovery period. PMID:26437675

  15. Monte Carlo simulation of light propagation in the adult brain

    NASA Astrophysics Data System (ADS)

    Mudra, Regina M.; Nadler, Andreas; Keller, Emanuella; Niederer, Peter

    2004-06-01

    When near infrared spectroscopy (NIRS) is applied noninvasively to the adult head for brain monitoring, extra-cerebral bone and surface tissue exert a substantial influence on the cerebral signal. Most attempts to subtract extra-cerebral contamination involve spatially resolved spectroscopy (SRS). However, inter-individual variability of anatomy restrict the reliability of SRS. We simulated the light propagation with Monte Carlo techniques on the basis of anatomical structures determined from 3D-magnetic resonance imaging (MRI) exhibiting a voxel resolution of 0.8 x 0.8 x 0.8 mm3 for three different pairs of T1/T2 values each. The MRI data were used to define the material light absorption and dispersion coefficient for each voxel. The resulting spatial matrix was applied in the Monte Carlo Simulation to determine the light propagation in the cerebral cortex and overlaying structures. The accuracy of the Monte Carlo Simulation was furthermore increased by using a constant optical path length for the photons which was less than the median optical path length of the different materials. Based on our simulations we found a differential pathlength factor (DPF) of 6.15 which is close to with the value of 5.9 found in the literature for a distance of 4.5cm between the external sensors. Furthermore, we weighted the spatial probability distribution of the photons within the different tissues with the probabilities of the relative blood volume within the tissue. The results show that 50% of the NIRS signal is determined by the grey matter of the cerebral cortex which allows us to conclude that NIRS can produce meaningful cerebral blood flow measurements providing that the necessary corrections for extracerebral contamination are included.

  16. The neural dynamics of song syntax in songbirds

    NASA Astrophysics Data System (ADS)

    Jin, Dezhe

    2010-03-01

    Songbird is ``the hydrogen atom'' of the neuroscience of complex, learned vocalizations such as human speech. Songs of Bengalese finch consist of sequences of syllables. While syllables are temporally stereotypical, syllable sequences can vary and follow complex, probabilistic syntactic rules, which are rudimentarily similar to grammars in human language. Songbird brain is accessible to experimental probes, and is understood well enough to construct biologically constrained, predictive computational models. In this talk, I will discuss the structure and dynamics of neural networks underlying the stereotypy of the birdsong syllables and the flexibility of syllable sequences. Recent experiments and computational models suggest that a syllable is encoded in a chain network of projection neurons in premotor nucleus HVC (proper name). Precisely timed spikes propagate along the chain, driving vocalization of the syllable through downstream nuclei. Through a computational model, I show that that variable syllable sequences can be generated through spike propagations in a network in HVC in which the syllable-encoding chain networks are connected into a branching chain pattern. The neurons mutually inhibit each other through the inhibitory HVC interneurons, and are driven by external inputs from nuclei upstream of HVC. At a branching point that connects the final group of a chain to the first groups of several chains, the spike activity selects one branch to continue the propagation. The selection is probabilistic, and is due to the winner-take-all mechanism mediated by the inhibition and noise. The model predicts that the syllable sequences statistically follow partially observable Markov models. Experimental results supporting this and other predictions of the model will be presented. We suggest that the syntax of birdsong syllable sequences is embedded in the connection patterns of HVC projection neurons.

  17. Transoceanic migration by a 12 g songbird

    PubMed Central

    DeLuca, William V.; Woodworth, Bradley K.; Rimmer, Christopher C.; Marra, Peter P.; Taylor, Philip D.; McFarland, Kent P.; Mackenzie, Stuart A.; Norris, D. Ryan

    2015-01-01

    Many fundamental aspects of migration remain a mystery, largely due to our inability to follow small animals over vast spatial areas. For more than 50 years, it has been hypothesized that, during autumn migration, blackpoll warblers (Setophaga striata) depart northeastern North America and undertake a non-stop flight over the Atlantic Ocean to either the Greater Antilles or the northeastern coast of South America. Using miniaturized light-level geolocators, we provide the first irrefutable evidence that the blackpoll warbler, a 12 g boreal forest songbird, completes an autumn transoceanic migration ranging from 2270 to 2770 km (mean ± s.d.: 2540 ± 257) and requiring up to 3 days (62 h ± 10) of non-stop flight. This is one of the longest non-stop overwater flights recorded for a songbird and confirms what has long been believed to be one of the most extraordinary migratory feats on the planet. PMID:25832815

  18. Transoceanic migration by a 12 g songbird.

    PubMed

    DeLuca, William V; Woodworth, Bradley K; Rimmer, Christopher C; Marra, Peter P; Taylor, Philip D; McFarland, Kent P; Mackenzie, Stuart A; Norris, D Ryan

    2015-04-01

    Many fundamental aspects of migration remain a mystery, largely due to our inability to follow small animals over vast spatial areas. For more than 50 years, it has been hypothesized that, during autumn migration, blackpoll warblers (Setophaga striata) depart northeastern North America and undertake a non-stop flight over the Atlantic Ocean to either the Greater Antilles or the northeastern coast of South America. Using miniaturized light-level geolocators, we provide the first irrefutable evidence that the blackpoll warbler, a 12 g boreal forest songbird, completes an autumn transoceanic migration ranging from 2270 to 2770 km (mean ± s.d.: 2540 ± 257) and requiring up to 3 days (62 h ± 10) of non-stop flight. This is one of the longest non-stop overwater flights recorded for a songbird and confirms what has long been believed to be one of the most extraordinary migratory feats on the planet. PMID:25832815

  19. Development of a Conceptual Model to Predict Physical Activity Participation in Adults with Brain Injuries

    ERIC Educational Resources Information Center

    Driver, Simon

    2008-01-01

    The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with…

  20. Future Concerns of Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Olney, Marjorie F.

    2008-01-01

    This study examined future concerns conveyed by adult siblings who provided regular caregiving support to their brothers and sisters with traumatic brain injury (TBI). The authors surveyed a national sample of 280 adult siblings of persons with TBI. Using a constant comparative approach to text analysis, the authors analyzed responses to the…

  1. The Social Environment and Neurogenesis in the Adult Mammalian Brain

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2012-01-01

    Adult neurogenesis – the formation of new neurons in adulthood – has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult–adult (e.g., mating and chemosensory interactions) and adult–offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant–subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed. PMID:22586385

  2. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    ERIC Educational Resources Information Center

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  3. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  4. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-01-01

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases. PMID:27098178

  5. Insulin-like growth factor I is required for vessel remodeling in the adult brain

    PubMed Central

    Lopez-Lopez, C.; LeRoith, D.; Torres-Aleman, I.

    2004-01-01

    Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1α and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum/brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction. PMID:15210967

  6. Redefining reproductive success in songbirds: Moving beyond the nest success paradigm

    USGS Publications Warehouse

    Streby, Henry M.; Refsnider, Jeanine M.; Andersen, David E.

    2014-01-01

    One of the most commonly estimated parameters in studies of songbird ecology is reproductive success, as a measure of either individual fitness or population productivity. Traditionally, the “success” in reproductive success refers to whether, or how many, nestlings leave nests. Here, we advocate that “reproductive success” in songbirds be redefined as full-season productivity, orthe number of young raised to independence from adult care in a breeding season. A growing body of evidence demonstrates interdependence between nest success and fledgling survival, and emphasizes that data from either life stage alone can produce misleading measures of individual fitness and population productivity. Nest success, therefore, is an insufficient measure of reproductive success, and songbird ecology needs to progress beyond this long-standing paradigm. Full-season productivity, an evolutionarily rational measure of reproductive success, provides the framework for appropriately addressing unresolved questions about the adaptive significance of many breeding behaviors and within which effective breeding-grounds conservation and management can be designed.

  7. BDNF Expression in Larval and Adult Zebrafish Brain: Distribution and Cell Identification

    PubMed Central

    Cacialli, Pietro; Gueguen, Marie-Madeleine; Coumailleau, Pascal; D’Angelo, Livia; Kah, Olivier; Lucini, Carla; Pellegrini, Elisabeth

    2016-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations. PMID:27336917

  8. High-resolution gene expression atlases for adult and developing mouse brain and spinal cord.

    PubMed

    Henry, Alex M; Hohmann, John G

    2012-10-01

    Knowledge of the structure, genetics, circuits, and physiological properties of the mammalian brain in both normal and pathological states is ever increasing as research labs worldwide probe the various aspects of brain function. Until recently, however, comprehensive cataloging of gene expression across the central nervous system has been lacking. The Allen Institute for Brain Science, as part of its mission to propel neuroscience research, has completed several large gene-mapping projects in mouse, nonhuman primate, and human brain, producing informative online public resources and tools. Here we present the Allen Mouse Brain Atlas, covering ~20,000 genes throughout the adult mouse brain; the Allen Developing Mouse Brain Atlas, detailing expression of approximately 2,000 important developmental genes across seven embryonic and postnatal stages of brain growth; and the Allen Spinal Cord Atlas, revealing expression for ~20,000 genes in the adult and neonatal mouse spinal cords. Integrated data-mining tools, including reference atlases, informatics analyses, and 3-D viewers, are described. For these massive-scale projects, high-throughput industrial techniques were developed to standardize and reliably repeat experimental goals. To verify consistency and accuracy, a detailed analysis of the 1,000 most viewed genes for the adult mouse brain (according to website page views) was performed by comparing our data with peer-reviewed literature and other databases. We show that our data are highly consistent with independent sources and provide a comprehensive compendium of information and tools used by thousands of researchers each month. All data and tools are freely available via the Allen Brain Atlas portal (www.brain-map.org). PMID:22832508

  9. A Comprehensive Account of Sound Sequence Imitation in the Songbird

    PubMed Central

    Westkott, Maren; Pawelzik, Klaus R.

    2016-01-01

    The amazing imitation capabilities of songbirds show that they can memorize sensory sequences and transform them into motor activities which in turn generate the original sound sequences. This suggests that the bird's brain can learn (1) to reliably reproduce spatio-temporal sensory representations and (2) to transform them into corresponding spatio-temporal motor activations by using an inverse mapping. Neither the synaptic mechanisms nor the network architecture enabling these two fundamental aspects of imitation learning are known. We propose an architecture of coupled neuronal modules that mimick areas in the song bird and show that a unique synaptic plasticity mechanism can serve to learn both, sensory sequences in a recurrent neuronal network, as well as an inverse model that transforms the sensory memories into the corresponding motor activations. The proposed membrane potential dependent learning rule together with the architecture that includes basic features of the bird's brain represents the first comprehensive account of bird imitation learning based on spiking neurons. PMID:27486395

  10. Acute brain slice methods for adult and aging animals: application of targeted patch clampanalysis and optogenetics

    PubMed Central

    Daigle, Tanya L.; Chen, Qian; Feng, Guoping

    2014-01-01

    Summary The development of the living acute brain slice preparation for analyzing synaptic function roughly a half century ago was a pivotal achievement that greatly influenced the landscape of modern neuroscience. Indeed, many neuroscientists regard brain slices as the gold-standard model system for detailed cellular, molecular, and circuitry level analysis and perturbation of neuronal function. A critical limitation of this model system is the difficulty in preparing slices from adult and aging animals, and over the past several decades few substantial methodological improvements have emerged to facilitate patch clamp analysis in the mature adult stage. In this chapter we describe a robust and practical protocol for preparing brain slices from mature adult mice that are suitable for patch clamp analysis. This method reduces swelling and damage in superficial layers of the slices and improves the success rate for targeted patch clamp recordings, including recordings from fluorescently labeled populations in slices derived from transgenic mice. This adult brain slice method is suitable for diverse experimental applications, including both monitoring and manipulating neuronal activity with genetically encoded calcium indicators and optogenetic actuators, respectively. We describe the application of this adult brain slice platform and associated methods for screening kinetic properties of Channelrhodopsin (ChR) variants expressed in genetically-defined neuronal subtypes. PMID:25023312

  11. Clonal development and organization of the adult Drosophila central brain

    PubMed Central

    Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David; Long, Fuhui; Yang, Jacob S.; He, Yisheng; Ding, Peng; Kao, Jui-Chun; Wu, Gloria Yueh-Yi; Peng, Hanchuan; Myers, Gene; Lee, Tzumin

    2013-01-01

    Summary Background The insect brain can be divided into neuropils that are formed by neurites of both local and remote origin. The complexity of the interconnections obscures how these neuropils are established and interconnected through development. The Drosophila central brain develops from a fixed number of neuroblasts (NBs) that deposit neurons in regional clusters. Results By determining individual NB clones and pursuing their projections into specific neuropils we unravel the regional development of the brain neural network. Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with characteristic cell body locations and neurite trajectories. Most clones show complex projection patterns, but despite the complexity, neighboring clones often co-innervate the same local neuropil(s) and further target a restricted set of distant neuropils. Conclusions These observations argue for regional clonal development of both neuropils and neuropil connectivity throughout the Drosophila central brain. PMID:23541733

  12. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  13. The opportunities and challenges of large-scale molecular approaches to songbird neurobiology

    PubMed Central

    Mello, C.V.; Clayton, D.F.

    2014-01-01

    High-through put methods for analyzing genome structure and function are having a large impact in song-bird neurobiology. Methods include genome sequencing and annotation, comparative genomics, DNA microarrays and transcriptomics, and the development of a brain atlas of gene expression. Key emerging findings include the identification of complex transcriptional programs active during singing, the robust brain expression of non-coding RNAs, evidence of profound variations in gene expression across brain regions, and the identification of molecular specializations within song production and learning circuits. Current challenges include the statistical analysis of large datasets, effective genome curations, the efficient localization of gene expression changes to specific neuronal circuits and cells, and the dissection of behavioral and environmental factors that influence brain gene expression. The field requires efficient methods for comparisons with organisms like chicken, which offer important anatomical, functional and behavioral contrasts. As sequencing costs plummet, opportunities emerge for comparative approaches that may help reveal evolutionary transitions contributing to vocal learning, social behavior and other properties that make songbirds such compelling research subjects. PMID:25280907

  14. The opportunities and challenges of large-scale molecular approaches to songbird neurobiology.

    PubMed

    Mello, C V; Clayton, D F

    2015-03-01

    High-throughput methods for analyzing genome structure and function are having a large impact in songbird neurobiology. Methods include genome sequencing and annotation, comparative genomics, DNA microarrays and transcriptomics, and the development of a brain atlas of gene expression. Key emerging findings include the identification of complex transcriptional programs active during singing, the robust brain expression of non-coding RNAs, evidence of profound variations in gene expression across brain regions, and the identification of molecular specializations within song production and learning circuits. Current challenges include the statistical analysis of large datasets, effective genome curations, the efficient localization of gene expression changes to specific neuronal circuits and cells, and the dissection of behavioral and environmental factors that influence brain gene expression. The field requires efficient methods for comparisons with organisms like chicken, which offer important anatomical, functional and behavioral contrasts. As sequencing costs plummet, opportunities emerge for comparative approaches that may help reveal evolutionary transitions contributing to vocal learning, social behavior and other properties that make songbirds such compelling research subjects. PMID:25280907

  15. Morphological brain network assessed using graph theory and network filtration in deaf adults.

    PubMed

    Kim, Eunkyung; Kang, Hyejin; Lee, Hyekyoung; Lee, Hyo-Jeong; Suh, Myung-Whan; Song, Jae-Jin; Oh, Seung-Ha; Lee, Dong Soo

    2014-09-01

    Prolonged deprivation of auditory input can change brain networks in pre- and postlingual deaf adults by brain-wide reorganization. To investigate morphological changes in these brains voxel-based morphometry, voxel-wise correlation with the primary auditory cortex, and whole brain network analyses using morphological covariance were performed in eight prelingual deaf, eleven postlingual deaf, and eleven hearing adults. Network characteristics based on graph theory and network filtration based on persistent homology were examined. Gray matter density in the primary auditor cortex was preserved in prelingual deafness, while it tended to decrease in postlingual deafness. Unlike postlingual, prelingual deafness showed increased bilateral temporal connectivity of the primary auditory cortex compared to the hearing adults. Of the graph theory-based characteristics, clustering coefficient, betweenness centrality, and nodal efficiency all increased in prelingual deafness, while all the parameters of postlingual deafness were similar to the hearing adults. Patterns of connected components changing during network filtration were different between prelingual deafness and hearing adults according to the barcode, dendrogram, and single linkage matrix representations, while these were the same in postlingual deafness. Nodes in fronto-limbic and left temporal components were closely coupled, and nodes in the temporo-parietal component were loosely coupled, in prelingual deafness. Patterns of connected components changing in postlingual deafness were the same as hearing adults. We propose that the preserved density of auditory cortex associated with increased connectivity in prelingual deafness, and closer coupling between certain brain areas, represent distinctive reorganization of auditory and related cortices compared with hearing or postlingual deaf adults. The differential network reorganization in the prelingual deaf adults could be related to the absence of auditory speech

  16. Event-related brain potentials - Comparison between children and adults

    NASA Technical Reports Server (NTRS)

    Courchesne, E.

    1977-01-01

    The reported investigation shows that nontarget stimuli which are infrequently presented and deviate from the background elicit Nc and Pc waves in children. The same stimuli elicit P3 waves in adults. The scalp distribution of P3 waves in adults appears to vary with the ease of stimulus recognition or the degree of stimulus novelty. However, the Nc and Pc distributions in children do not seem to vary with these factors. The differences between children and adults in event-related potentials suggest corresponding differences in the mode of processing employed by each when rare, deviant stimuli are encountered

  17. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed Central

    Xu, Feng; Liu, Peiying; Pekar, James J.; Lu, Hanzhang

    2015-01-01

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain’s response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine’s effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  18. A revised dosimetric model of the adult head and brain

    SciTech Connect

    Bouchet, L.G.; Bolch, W.E.; Weber, D.A.; Atkins, H.L.; Poston, J.W. ||

    1996-07-01

    During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificicity within the brain and their increasing use for diagnostic studies support the need for a more antihropomorphic model of the human brain and head. Brain and head models developed in the past have comprised only simplistic representations of this anatomic region. A new brain model has been developed which includes eight subregions: the caudate nucleus, the cerebellium, the cerebral cortex, the lateral ventricles, the lentiform nucleus, the thalamus, the third ventricle and the white matter. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. The head model, which includes both the thyroid and eyes, was modified in this work to include the cerebrospinal fluid within the cranial and spinal regions. Absorbed fractions of energy for photon and electron sources located in thirteen source regions within the new head model were calculated using the EGS4 Monte Carlo radiation transport code for radiations in the energy range 10 keV to 4 MeV. S-values were calculated for five radionuclides used in brain imaging ({sup 11}C, {sup 15}O, {sup 18}F, {sup 99m}Tc and {sup 123}I) and for three radionuclides showing selective uptake in the thyroid ({sup 99m}Tc, {sup 123}I, and {sup 131}I). S-values were calculated using 100 discrete energy points in the beta-emission spectrum of the different radionuclides. 17 refs., 14 figs., 3 tabs.

  19. aBEAT: a toolbox for consistent analysis of longitudinal adult brain MRI.

    PubMed

    Dai, Yakang; Wang, Yaping; Wang, Li; Wu, Guorong; Shi, Feng; Shen, Dinggang

    2013-01-01

    Longitudinal brain image analysis is critical for revealing subtle but complex structural and functional changes of brain during aging or in neurodevelopmental disease. However, even with the rapid increase of clinical research and trials, a software toolbox dedicated for longitudinal image analysis is still lacking publicly. To cater for this increasing need, we have developed a dedicated 4D Adult Brain Extraction and Analysis Toolbox (aBEAT) to provide robust and accurate analysis of the longitudinal adult brain MR images. Specially, a group of image processing tools were integrated into aBEAT, including 4D brain extraction, 4D tissue segmentation, and 4D brain labeling. First, a 4D deformable-surface-based brain extraction algorithm, which can deform serial brain surfaces simultaneously under temporal smoothness constraint, was developed for consistent brain extraction. Second, a level-sets-based 4D tissue segmentation algorithm that incorporates local intensity distribution, spatial cortical-thickness constraint, and temporal cortical-thickness consistency was also included in aBEAT for consistent brain tissue segmentation. Third, a longitudinal groupwise image registration framework was further integrated into aBEAT for consistent ROI labeling by simultaneously warping a pre-labeled brain atlas to the longitudinal brain images. The performance of aBEAT has been extensively evaluated on a large number of longitudinal MR T1 images which include normal and dementia subjects, achieving very promising results. A Linux-based standalone package of aBEAT is now freely available at http://www.nitrc.org/projects/abeat. PMID:23577105

  20. Development of a conceptual model to predict physical activity participation in adults with brain injuries.

    PubMed

    Driver, Simon

    2008-10-01

    The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with brain injuries completed a series of questionnaires measuring each psychosocial variable. The structural analysis indicated a nonsignificant chi squared value and good fit indices for model two which included affect as the mediating variable. Findings indicate that affect is critical in shaping the physical activity cognitions and behaviors of adults with brain injuries. Suggestions are made on practical ways to enhance affect and subsequently physical activity participation. PMID:18955746

  1. Ephrin/Eph receptor expression in brain of adult nonhuman primates: implications for neuroadaptation.

    PubMed

    Xiao, Danqing; Miller, Gregory M; Jassen, Amy; Westmoreland, Susan V; Pauley, Douglas; Madras, Bertha K

    2006-01-01

    In developing brain, Eph receptors and their ephrin ligands (Ephs/ephrins) are implicated in facilitating topographic guidance of a number of pathways, including the nigrostriatal and mesolimbic dopamine (DA) pathways. In adult rodent brain, these molecules are implicated in neuronal plasticity associated with learning and memory. Cocaine significantly alters the expression of select members of this family of axonal guidance molecules, implicating Ephs, ephrins in drug-induced neuroadaptation. The potential contribution of Ephs, ephrins to cocaine-induced reorganization of striatal circuitry brain in primates [Saka, E., Goodrich, C., Harlan, P., Madras, B.K., Graybiel, A.M., 2004. Repetitive behaviors in monkeys are linked to specific striatal activation patterns. J. Neurosci. 24, 7557-7565] is unknown because there are no documented reports of Eph/ephrin expression or function in adult primate brain. We now report that brains of adult old and new world monkeys express mRNA encoding EphA4 receptor and ephrin-B2 ligand, implicated in topographic guidance of dopamine and striatal neurons during development. Their encoded proteins distributed highly selectively in regions of adult monkey brain. EphA4 mRNA levels were prominent in the DA-rich caudate/putamen, nucleus accumbens and globus pallidus, as well as the medial and orbitofrontal cortices, hippocampus, amygdala, thalamus and cerebellum. Immunocytochemical localization of EphA4 protein revealed discrete expression in caudate/putamen, globus pallidus, substantia nigra, cerebellar Purkinje cells, pyramidal cells of frontal cortices (layers II, III and V) and the subgranular zone of the hippocampus. Evidence for EphA4 expression in dopamine neurons emerged from colocalization with tyrosine-hydroxylase-positive terminals in striatum and substantia nigra and ventral tegmental area cell bodies. The association of axonal guidance molecules with drug-induced reorganization of adult primate brain circuitry warrants

  2. Localization of PPAR isotypes in the adult mouse and human brain

    PubMed Central

    Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron

    2016-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430

  3. Using Network Science to Evaluate Exercise-Associated Brain Changes in Older Adults

    PubMed Central

    Burdette, Jonathan H.; Laurienti, Paul J.; Espeland, Mark A.; Morgan, Ashley; Telesford, Qawi; Vechlekar, Crystal D.; Hayasaka, Satoru; Jennings, Janine M.; Katula, Jeffrey A.; Kraft, Robert A.; Rejeski, W. Jack

    2010-01-01

    Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise. PMID:20589103

  4. Brain function differences in language processing in children and adults with autism.

    PubMed

    Williams, Diane L; Cherkassky, Vladimir L; Mason, Robert A; Keller, Timothy A; Minshew, Nancy J; Just, Marcel Adam

    2013-08-01

    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. PMID:23495230

  5. Brain Function Differences in Language Processing in Children and Adults with Autism

    PubMed Central

    Williams, Diane L.; Cherkassky, Vladimir L.; Mason, Robert A.; Keller, Timothy A.; Minshew, Nancy J.; Just, Marcel Adam

    2015-01-01

    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. PMID:23495230

  6. Conservation and expression of IQ-domain-containing calpacitin gene products (Neuromodulin/GAP-43, Neurogranin/RC3) in the adult and developing oscine song control system

    PubMed Central

    Clayton, David F.; George, Julia M.; Mello, Claudio V.; Siepka, Sandra M.

    2009-01-01

    Songbirds are appreciated for the insights they provide into regulated neural plasticity. Here we describe the comparative analysis and brain expression of two gene sequences encoding probable regulators of synaptic plasticity in songbirds: Neuromodulin (GAP-43) and Neurogranin (RC3). Both are members of the calpacitin family and share a distinctive conserved core domain that mediates interactions between calcium, calmodulin and protein kinase C signaling pathways. Comparative sequence analysis is consistent with known phylogenetic relationships, with songbirds most closely related to chicken and progressively more distant from mammals and fish. The C-terminus of Neurogranin is different in birds and mammals, and antibodies to the protein reveal high expression in adult zebra finches in cerebellar Purkinje cells, which has not been observed in other species. RNAs for both proteins are generally abundant in the telencephalon yet markedly reduced in certain nuclei of the song control system in adult canaries and zebra finches: Neuromodulin RNA is very low in RA and HVC (relative to the surrounding pallial areas), whereas Neurogranin RNA is conspicuously low in Area X (relative to surrounding striatum). In both cases, this selective down-regulation develops in the zebra finch during the juvenile song learning period, 25–45 days after hatching. These results suggest molecular parallels to the robust stability of the adult avian song control circuit. PMID:19023859

  7. Educating the adult brain: How the neuroscience of learning can inform educational policy

    NASA Astrophysics Data System (ADS)

    Knowland, Victoria C. P.; Thomas, Michael S. C.

    2014-05-01

    The acquisition of new skills in adulthood can positively affect an individual's quality of life, including their earning potential. In some cases, such as the learning of literacy in developing countries, it can provide an avenue to escape from poverty. In developed countries, job retraining in adulthood contributes to the flexibility of labour markets. For all adults, learning opportunities increase participation in society and family life. However, the popular view is that adults are less able to learn for an intrinsic reason: their brains are less plastic than in childhood. This article reviews what is currently known from neuroscientific research about how brain plasticity changes with age, with a particular focus on the ability to acquire new skills in adulthood. Anchoring their review in the examples of the adult acquisition of literacy and new motor skills, the authors address five specific questions: (1) Are sensitive periods in brain development relevant to learning complex educational skills like literacy? (2) Can adults become proficient in a new skill? (3) Can everyone learn equally effectively in adulthood? (4) What is the role of the learning environment? (5) Does adult education cost too much? They identify areas where further research is needed and conclude with a summary of principles for enhancing adult learning now established on a neuroscience foundation.

  8. The effects of sleep deprivation on brain functioning in older adults.

    PubMed

    Almklov, Erin L; Drummond, Sean P A; Orff, Henry; Alhassoon, Omar M

    2015-01-01

    Few studies have examined the effects of total sleep deprivation (TSD) on cognitive performance and brain activation using functional MRI (fMRI) in older adults. The current study examines blood oxygen level-dependent (BOLD) activation in older adults and younger adults during the sustained attention (GO) and response inhibition (NOGO) portions of a GO-NOGO cognitive task following 36 hr of total sleep deprivation. No significant performance differences were observed between the groups on the behavioral outcome measures of total hits and false alarms. Neuroimaging results, however, revealed a significant interaction between age-group and sleep-deprivation status. Specifically, older adults showed greater BOLD activation as compared to younger adults after 36 hours total sleep deprivation in brain regions typically associated with attention and inhibitory processes. These results suggest in order for older adults to perform the GO-NOGO task effectively after sleep deprivation, they rely on compensatory recruitment of brain regions that aide in the maintenance of cognitive performance. PMID:24787041

  9. Tracking from the Tropics Reveals Behaviour of Juvenile Songbirds on Their First Spring Migration

    PubMed Central

    McKinnon, Emily A.; Fraser, Kevin C.; Stanley, Calandra Q.; Stutchbury, Bridget J. M.

    2014-01-01

    Juvenile songbirds on spring migration travel from tropical wintering sites to temperate breeding destinations thousands of kilometres away with no prior experience to guide them. We provide a first glimpse at the migration timing, routes, and stopover behaviour of juvenile wood thrushes (Hylocichla mustelina) on their inaugural spring migration by using miniaturized archival geolocators to track them from Central America to the U.S. and Canada. We found significant differences between the timing of juvenile migration and that of more experienced adults: juveniles not only departed later from tropical wintering sites relative to adults, they also became progressively later as they moved northward. The increasing delay was driven by more frequent short stops by juveniles along their migration route, particularly in the U.S. as they got closer to breeding sites. Surprisingly, juveniles were just as likely as adults to cross the Gulf of Mexico, an open-water crossing of 800–1000 km, and migration route at the Gulf was not significantly different for juveniles relative to adults. To determine if the later departure of juveniles was related to poor body condition in winter relative to adults, we examined percent lean body mass, fat scores, and pectoral muscle scores of juvenile versus adult birds at a wintering site in Belize. We found no age-related differences in body condition. Later migration timing of juveniles relative to adults could be an adaptive strategy (as opposed to condition-dependent) to avoid the high costs of fast migration and competition for breeding territories with experienced and larger adults. We did find significant differences in wing size between adults and juveniles, which could contribute to lower flight efficiency of juveniles and thus slower overall migration speed. We provide the first step toward understanding the “black box” of juvenile songbird migration by documenting their migration timing and en route performance. PMID:25141193

  10. Vitamin D as a neurosteroid affecting the developing and adult brain.

    PubMed

    Groves, Natalie J; McGrath, John J; Burne, Thomas H J

    2014-01-01

    Vitamin D deficiency is prevalent throughout the world, and growing evidence supports a requirement for optimal vitamin D levels for the healthy developing and adult brain. Vitamin D has important roles in proliferation and differentiation, calcium signaling within the brain, and neurotrophic and neuroprotective actions; it may also alter neurotransmission and synaptic plasticity. Recent experimental studies highlight the impact that vitamin D deficiency has on brain function in health and disease. In addition, results from recent animal studies suggest that vitamin D deficiency during adulthood may exacerbate underlying brain disorders and/or worsen recovery from brain stressors. An increasing number of epidemiological studies indicate that vitamin D deficiency is associated with a wide range of neuropsychiatric disorders and neurodegenerative diseases. Vitamin D supplementation is readily available and affordable, and this review highlights the need for further research. PMID:25033060

  11. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

  12. Amphetamine modulates brain signal variability and working memory in younger and older adults

    PubMed Central

    Garrett, Douglas D.; Nagel, Irene E.; Preuschhof, Claudia; Burzynska, Agnieszka Z.; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J.; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R.; Bäckman, Lars; Lindenberger, Ulman

    2015-01-01

    Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI–based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change–change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics. PMID:26034283

  13. Structural and functional rich club organization of the brain in children and adults.

    PubMed

    Grayson, David S; Ray, Siddharth; Carpenter, Samuel; Iyer, Swathi; Dias, Taciana G Costa; Stevens, Corinne; Nigg, Joel T; Fair, Damien A

    2014-01-01

    Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism. PMID:24505468

  14. Regulation of brain water during acute glucose-induced hyperosmolality in ovine fetuses, lambs, and adults.

    PubMed

    Stonestreet, Barbara S; Petersson, Katherine H; Sadowska, Grazyna B; Patlak, Clifford S

    2004-02-01

    We tested the hypothesis that, during acute glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and that brain volume regulation is present in fetuses, premature and newborn lambs. Brain water responses to glucose-induced hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After exposure of the sheep to increases in osmolality with glucose plus NaCl, brain water and electrolytes were measured. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. In the absence of volume regulation, brain solute remains constant as osmolality changes. The osmotically active solute demonstrated direct linear correlations with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation (r = 0.72, n = 24, P = 0.0001), premature lambs (r = 0.58, n = 22, P = 0.005), newborn lambs (r = 0.57, n = 24, P = 0.004), and adult sheep (r = 0.70, n = 18, P = 0.001). Similar findings were observed in the cerebellum and medulla. Increases in the quantity of osmotically active solute over the range of plasma osmolalities indicate that volume regulation was present in the brain regions of the fetuses, premature lambs, newborn lambs, and adult sheep during glucose-induced hyperosmolality. We conclude that, during glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and exhibits volume regulation in fetuses at 60% of gestation, premature lambs, newborn lambs, and adult sheep. PMID:14578364

  15. Regeneration, Plasticity, and Induced Molecular Programs in Adult Zebrafish Brain

    PubMed Central

    Cosacak, Mehmet Ilyas; Papadimitriou, Christos; Kizil, Caghan

    2015-01-01

    Regenerative capacity of the brain is a variable trait within animals. Aquatic vertebrates such as zebrafish have widespread ability to renew their brains upon damage, while mammals have—if not none—very limited overall regenerative competence. Underlying cause of such a disparity is not fully evident; however, one of the reasons could be activation of peculiar molecular programs, which might have specific roles after injury or damage, by the organisms that regenerate. If this hypothesis is correct, then there must be genes and pathways that (a) are expressed only after injury or damage in tissues, (b) are biologically and functionally relevant to restoration of neural tissue, and (c) are not detected in regenerating organisms. Presence of such programs might circumvent the initial detrimental effects of the damage and subsequently set up the stage for tissue redevelopment to take place by modulating the plasticity of the neural stem/progenitor cells. Additionally, if transferable, those “molecular mechanisms of regeneration” could open up new avenues for regenerative therapies of humans in clinical settings. This review focuses on the recent studies addressing injury/damage-induced molecular programs in zebrafish brain, underscoring the possibility of the presence of genes that could be used as biomarkers of neural plasticity and regeneration. PMID:26417601

  16. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  17. Canonical genetic signatures of the adult human brain.

    PubMed

    Hawrylycz, Michael; Miller, Jeremy A; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L; Jegga, Anil G; Aronow, Bruce J; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F; Dierker, Donna L; Menche, Jörg; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R; Jones, Allan; Van Essen, David C; Koch, Christof; Lein, Ed

    2015-12-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  18. A Statistical Method for Quantifying Songbird Phonology and Syntax

    PubMed Central

    Wu, Wei; Thompson, John A.; Bertram, Richard; Johnson, Frank

    2008-01-01

    Songbirds are the preeminent animal model for understanding how the brain encodes and produces learned vocalizations. Here, we report a new statistical method, the Kullback-Leibler (K-L) distance, for analyzing vocal change over time. First, we use a computerized recording system to capture all song syllables produced by birds each day. Sound Analysis Pro software (Tchernichovski et al., 2000) is then used to measure the duration of each syllable as well as four spectral features: pitch, entropy, frequency modulation, and pitch goodness. Next, 2-dimensional scatter plots of each day of singing are created where syllable duration is on the x-axis and each of the spectral features is represented separately on the y-axis. Each point in the scatter plots represents one syllable and we regard these plots as random samples from a probability distribution. We then apply the standard information-theoretic quantity K-L distance to measure dissimilarity in phonology across days of singing. A variant of this procedure can also be used to analyze differences in syllable syntax. PMID:18674560

  19. Genetic Methods to Identify and Manipulate Newly Born Neurons in the Adult Brain

    PubMed Central

    Imayoshi, Itaru; Sakamoto, Masayuki; Kageyama, Ryoichiro

    2011-01-01

    Although mammalian neurogenesis is mostly completed by the perinatal period, new neurons are continuously generated in the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. Since the discovery of adult neurogenesis, many extensive studies have been performed on various aspects of adult neurogenesis, including proliferation and fate-specification of adult neural stem cells, and the migration, maturation and synaptic integration of newly born neurons. Furthermore, recent research has shed light on the intensive contribution of adult neurogenesis to olfactory-related and hippocampus-mediated brain functions. The field of adult neurogenesis progressed tremendously thanks to technical advances that facilitate the identification and selective manipulation of newly born neurons among billions of pre-existing neurons in the adult central nervous system. In this review, we introduce recent advances in the methodologies for visualizing newly generated neurons and manipulating neurogenesis in the adult brain. Particularly, the application of site-specific recombinases and Tet inducible system in combination with transgenic or gene targeting strategy is discussed in further detail. PMID:21562606

  20. Brain Blood Flow Related to Acoustic Laryngeal Reaction Time in Adult Developmental Stutterers.

    ERIC Educational Resources Information Center

    Watson, Ben C.; And Others

    1992-01-01

    This study sought to identify patterns of impaired acoustic laryngeal reaction time as a function of response complexity parallel to metabolic measures of brain function. Findings indicated that the disruption in speech motor control for 16 adult male developmental stutterers was systematically related to metabolic asymmetry in left superior and…

  1. Brain Mapping of Language and Auditory Perception in High-Functioning Autistic Adults: A PET Study.

    ERIC Educational Resources Information Center

    Muller, R-A.; Behen, M. E.; Rothermel, R. D.; Chugani, D. C.; Muzik, O.; Mangner, T. J.; Chugani, H. T.

    1999-01-01

    A study used positron emission tomography (PET) to study patterns of brain activation during auditory processing in five high-functioning adults with autism. Results found that participants showed reversed hemispheric dominance during the verbal auditory stimulation and reduced activation of the auditory cortex and cerebellum. (CR)

  2. Humor, Rapport, and Uncomfortable Moments in Interactions with Adults with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kovarsky, Dana; Schiemer, Christine; Murray, Allison

    2011-01-01

    We examined uncomfortable moments that damaged rapport during group interactions between college students in training to become speech-language pathologists and adults with traumatic brain injury. The students worked as staff in a community-based program affiliated with a university training program that functioned as a recreational gathering…

  3. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  4. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    PubMed Central

    Zheng, Zhiwei; Zhu, Xinyi; Yin, Shufei; Wang, Baoxi; Niu, Yanan; Huang, Xin; Li, Rui; Li, Juan

    2015-01-01

    Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age. PMID:25810927

  5. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    PubMed

    King, Tricia Z; Na, Sabrina; Mao, Hui

    2015-08-01

    Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory. PMID:26234757

  6. Food Provisioning and Parental Status in Songbirds: Can Occupancy Models Be Used to Estimate Nesting Performance?

    PubMed Central

    Corbani, Aude Catherine; Hachey, Marie-Hélène; Desrochers, André

    2014-01-01

    Indirect methods to estimate parental status, such as the observation of parental provisioning, have been problematic due to potential biases associated with imperfect detection. We developed a method to evaluate parental status based on a novel combination of parental provisioning observations and hierarchical modeling. In the summers of 2009 to 2011, we surveyed 393 sites, each on three to four consecutive days at Forêt Montmorency, Québec, Canada. We assessed parental status of 2331 adult songbirds based on parental food provisioning. To account for imperfect detection of parental status, we applied MacKenzie et al.'s (2002) two-state hierarchical model to obtain unbiased estimates of the proportion of sites with successfully nesting birds, and the proportion of adults with offspring. To obtain an independent evaluation of detection probability, we monitored 16 active nests in 2010 and conducted parental provisioning observations away from them. The probability of detecting food provisioning was 0.31 when using nest monitoring, a value within the 0.11 to 0.38 range that was estimated by two-state models. The proportion of adults or sites with broods approached 0.90 and varied depending on date during the sampling season and year, exemplifying the role of eastern boreal forests as highly productive nesting grounds for songbirds. This study offers a simple and effective sampling design for studying avian reproductive performance that could be implemented in national surveys such as breeding bird atlases. PMID:24999969

  7. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche.

    PubMed

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V; Sun, Bin; Dizon, Maria L V; Szele, Francis G

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  8. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

    PubMed Central

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V.; Sun, Bin; Dizon, Maria L. V.; Szele, Francis G.

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  9. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-01-01

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells. PMID:27259217

  10. Social performance reveals unexpected vocal competency in young songbirds

    PubMed Central

    Kojima, Satoshi; Doupe, Allison J.

    2011-01-01

    Vocal ontogeny in songbirds provides a good model for understanding how complex motor behavior, including speech, is learned. For birdsong, as for other motor learning, it has generally been assumed that a subject's motor output at any point during learning represents what the subject has learned to produce by that time. Here, we show, however, that juvenile zebra finches partway through song learning, singing immature song, are capable of producing song with much more mature properties, depending on the behavioral context. In these birds, we were able to elicit courtship (female-directed) song, which young birds normally sing infrequently, and to compare it with the alone or “undirected” song (Undir) predominantly produced during learning as well as with the same bird's subsequent adult song. We found that the juvenile courtship song was much less variable than the immature Undir and as stereotyped as the adult song produced after a further month of practice. More strikingly, the juvenile courtship song was also acoustically much more similar than Undir to the adult song. This finding demonstrates that the Undir that juvenile birds usually produce underestimates the extent of learning and that song structure is learned faster than previously thought. Moreover, the rapid improvement in song quality in response to external social cues supports the idea that courtship singing is a state of motor “performance,” in which the bird selects the best variants of the song learned during singing alone, and suggests that such performance states can reveal unappreciated progression of learning. PMID:21220335

  11. Quantitative Expression Profile of Distinct Functional Regions in the Adult Mouse Brain

    PubMed Central

    Nagano, Mamoru; Uno, Kenichiro D.; Tsujino, Kaori; Hanashima, Carina; Shigeyoshi, Yasufumi; Ueda, Hiroki R.

    2011-01-01

    The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B*) project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems. PMID:21858037

  12. Rapid and efficient gene delivery into the adult mouse brain via focal electroporation

    PubMed Central

    Nomura, Tadashi; Nishimura, Yusuke; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    In vivo gene delivery is required for studying the cellular and molecular mechanisms of various biological events. Virus-mediated gene transfer or generation of transgenic animals is widely used; however, these methods are time-consuming and expensive. Here we show an improved electroporation technique for acute gene delivery into the adult mouse brain. Using a syringe-based microelectrode, local DNA injection and the application of electric current can be performed simultaneously; this allows rapid and efficient gene transduction of adult non-neuronal cells. Combining this technique with various expression vectors that carry specific promoters resulted in targeted gene expression in astrocytic cells. Our results constitute a powerful strategy for the genetic manipulation of adult brains in a spatio-temporally controlled manner. PMID:27430903

  13. Rapid and efficient gene delivery into the adult mouse brain via focal electroporation.

    PubMed

    Nomura, Tadashi; Nishimura, Yusuke; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    In vivo gene delivery is required for studying the cellular and molecular mechanisms of various biological events. Virus-mediated gene transfer or generation of transgenic animals is widely used; however, these methods are time-consuming and expensive. Here we show an improved electroporation technique for acute gene delivery into the adult mouse brain. Using a syringe-based microelectrode, local DNA injection and the application of electric current can be performed simultaneously; this allows rapid and efficient gene transduction of adult non-neuronal cells. Combining this technique with various expression vectors that carry specific promoters resulted in targeted gene expression in astrocytic cells. Our results constitute a powerful strategy for the genetic manipulation of adult brains in a spatio-temporally controlled manner. PMID:27430903

  14. Removing brakes on adult brain plasticity: from molecular to behavioral interventions

    PubMed Central

    Bavelier, D.; Levi, D.M.; Li, R.W.; Dan, Y.; Hensch, T.K.

    2010-01-01

    Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as peri-neuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects. PMID:21068299

  15. Regional Brain Volumes and ADHD Symptoms in Middle-Aged Adults: The PATH Through Life Study.

    PubMed

    Das, Debjani; Cherbuin, Nicolas; Anstey, Kaarin J; Abhayaratna, Walter; Easteal, Simon

    2014-02-24

    Objective: We investigated whether volumetric differences in ADHD-associated brain regions are related to current symptoms of inattention and hyperactivity in healthy middle-aged adults and whether co-occurring anxiety/depression symptoms moderate these relationships. Method: ADHD Self-Report Scale and Brief Patient Health Questionnaire were used to assess current symptoms of inattention, hyperactivity, anxiety, and depression in a population-based sample (n = 269). Brain volumes, measured using a semi-automated method, were analyzed using multiple regression and structural equation modeling to evaluate brain volume-inattention/hyperactivity symptom relationships for selected regions. Results: Volumes of the left nucleus accumbens and a region overlapping the dorsolateral prefrontal cortex were positively associated with inattention symptoms. Left hippocampal volume was negatively associated with hyperactivity symptoms. The brain volume-inattention/hyperactivity symptom associations were stronger when anxiety/depression symptoms were controlled for. Conclusion: Inattention and hyperactivity symptoms in middle-aged adults are associated with different brain regions and co-occurring anxiety/depression symptoms moderate these brain-behavior relationships. (J. of Att. Dis. XXXX; XX(X) XX-XX). PMID:24567365

  16. Analgesic use and the risk of primary adult brain tumor.

    PubMed

    Egan, Kathleen M; Nabors, Louis B; Thompson, Zachary J; Rozmeski, Carrie M; Anic, Gabriella A; Olson, Jeffrey J; LaRocca, Renato V; Chowdhary, Sajeel A; Forsyth, Peter A; Thompson, Reid C

    2016-09-01

    Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma. PMID:26894804

  17. Brain Pathology in Adult Rats Treated With Domoic Acid.

    PubMed

    Vieira, A C; Alemañ, N; Cifuentes, J M; Bermúdez, R; Peña, M López; Botana, L M

    2015-11-01

    Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain. PMID:25939577

  18. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    ClinicalTrials.gov

    2016-09-07

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  19. Rejecting familiar distracters during recognition in young adults with traumatic brain injury and in healthy older adults.

    PubMed

    Ozen, Lana J; Skinner, Erin I; Fernandes, Myra A

    2010-05-01

    The most common cognitive complaint reported by healthy older adults and young adults with traumatic brain injury (TBI) is memory difficulties. We investigated the effects of normal aging and the long-term effects of TBI in young adults on the susceptibility to incorrectly endorse distracter information on a memory test. Prior to a study phase, participants viewed a "pre-exposure" list containing distracter words, presented once or three times, and half of the target study words. Subsequently, during the study phase, all target words were presented such that, across lists, study words were viewed either once or three times. On the recognition test, TBI and older adult participants were more likely to falsely endorse "pre-exposed" distracter words viewed three times as being from the target study list, compared to non-head-injured young controls. Normal aging and head injury in young may similarly compromise one's ability to reject highly familiar, but distracting, information during recognition. Older adult and TBI participants were also slower to complete the Trail Making task and had poorer output on a Digit Span task, suggesting these two populations share a deficit in executive function and working memory. Similar changes in frontal lobe function may underlie these shared cognitive deficits. PMID:20211048

  20. Evaluation of a Reading Comprehension Strategy Package to Improve Reading Comprehension of Adult College Students with Acquired Brain Injuries

    ERIC Educational Resources Information Center

    Griffiths, Gina G.

    2013-01-01

    Adults with mild to moderate acquired brain injury (ABI) often pursue post-secondary or professional education after their injuries in order to enter or re-enter the job market. An increasing number of these adults report problems with reading-to-learn. The problem is particularly concerning given the growing population of adult survivors of ABI.…

  1. A productivity model for parasitized, multibrooded songbirds

    USGS Publications Warehouse

    Powell, L.A.; Knutson, M.G.

    2006-01-01

    We present an enhancement of a simulation model to predict annual productivity for Wood Thrushes (Hylocichla mustelina) and American Redstarts (Setophaga ruticilla); the model includes effects of Brown-headed Cowbird (Molothrus ater) parasitism. We used species-specific data from the Driftless Area Ecoregion of Wisconsin, Minnesota, and Iowa to parameterize the model as a case study. The simulation model predicted annual productivity of 2.03 ?? 1.60 SD for Wood Thrushes and 1.56 ?? 1.31 SD for American Redstarts. Our sensitivity analysis showed that high parasitism lowered Wood Thrush annual productivity more than American Redstart productivity, even though parasitism affected individual nests of redstarts more severely. Annual productivity predictions are valuable for habitat managers, but productivity is not easily obtained from field studies. Our model provides a useful means of integrating complex life history parameters to predict productivity for songbirds that experience nest parasitism. ?? The Cooper Ornithological Society 2006.

  2. Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

    PubMed Central

    Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.

    2016-01-01

    Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680

  3. Sleep and synaptic plasticity in the developing and adult brain.

    PubMed

    Frank, Marcos G

    2015-01-01

    Sleep is hypothesized to play an integral role in brain plasticity. This has traditionally been investigated using behavioral assays. In the last 10-15 years, studies combining sleep measurements with in vitro and in vivo models of synaptic plasticity have provided exciting new insights into how sleep alters synaptic strength. In addition, new theories have been proposed that integrate older ideas about sleep function and recent discoveries in the field of synaptic plasticity. There remain, however, important challenges and unanswered questions. For example, sleep does not appear to have a single effect on synaptic strength. An unbiased review of the literature indicates that the effects of sleep vary widely depending on ontogenetic stage, the type of waking experience (or stimulation protocols) that precede sleep and the type of neuronal synapse under examination. In this review, I discuss these key findings in the context of current theories that posit different roles for sleep in synaptic plasticity. PMID:24671703

  4. Neural imaging in songbirds using fiber optic fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Nooshabadi, Fatemeh; Hearn, Gentry; Lints, Thierry; Maitland, Kristen C.

    2012-02-01

    The song control system of juvenile songbirds is an important model for studying the developmental acquisition and generation of complex learned vocal motor sequences, two processes that are fundamental to human speech and language. To understand the neural mechanisms underlying song production, it is critical to characterize the activity of identified neurons in the song control system when the bird is singing. Neural imaging in unrestrained singing birds, although technically challenging, will advance our understanding of neural ensemble coding mechanisms in this system. We are exploring the use of a fiber optic microscope for functional imaging in the brain of behaving and singing birds in order to better understand the contribution of a key brain nucleus (high vocal center nucleus; HVC) to temporal aspects of song motor control. We have constructed a fluorescence microscope with LED illumination, a fiber bundle for transmission of fluorescence excitation and emission light, a ~2x GRIN lens, and a CCD for image acquisition. The system has 2 μm resolution, 375 μm field of view, 200 μm working distance, and 1 mm outer diameter. As an initial characterization of this setup, neurons in HVC were imaged using the fiber optic microscope after injection of quantum dots or fluorescent retrograde tracers into different song nuclei. A Lucid Vivascope confocal microscope was used to confirm the imaging results. Long-term imaging of the activity of these neurons in juvenile birds during singing may lead us to a better understanding of the central motor codes for song and the central mechanism by which auditory experience modifies song motor commands to enable vocal learning and imitation.

  5. Brain metabolite concentrations across cortical regions in healthy adults

    PubMed Central

    Bracken, Bethany K.; Jensen, J. Eric; Prescot, Andrew P.; Cohen, Bruce M.; Renshaw, Perry F.; Öngür, Dost

    2010-01-01

    Magnetic resonance spectroscopy (MRS) can provide in vivo information about metabolite levels across multiple brain regions. This study used MRS to examine concentrations of N-acetylaspartate (NAA), a marker of neuronal integrity and function, and choline (Cho) which is related to the amount of cell membrane per unit volume, in anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) in healthy individuals. Data were drawn from two experiments which examined glutamatergic and GABAergic signaling in schizophrenia and bipolar disorder. After controlling for gray matter percentages, NAA/Creatine (Cr) was 18% higher in POC than in ACC (p<0.001); Cho/Cr was 46% lower in POC than in ACC (p<0.001). There was an effect of study (p<0.001 for both metabolites), but no region by study interaction (NAA p=0.101, Cho p=0.850). Since NAA is localized to the intracellular space, these data suggest that ACC neuronal compartment is reduced as compared with POC, or that there is a lower concentration of NAA per cell in the ACC than POC, or both. Since elevated Cho suggests more cell membrane per unit volume, reduced NAA in ACC appears to be coupled with increases in overall cell membrane compartment. These findings are consistent with a number of previous studies using proton MRS which found increasing NAA and decreasing Cho moving caudally, and with post mortem anatomical studies which found neurons in more widely spaced bundles in ACC when compared to parietal and occipital cortices. MRS may be a useful tool for studying physical properties of the living human brain. PMID:21081116

  6. Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction

    PubMed Central

    De Jesús Andino, Francisco; Jones, Letitia; Maggirwar, Sanjay B.; Robert, Jacques

    2016-01-01

    While increasing evidence points to a key role of monocytes in amphibian host defenses, monocytes are also thought to be important in the dissemination and persistent infection caused by ranavirus. However, little is known about the fate of infected macrophages or if ranavirus exploits immune privileged organs, such as the brain, in order to establish a reservoir. The amphibian Xenopus laevis and Frog Virus 3 (FV3) were established as an experimental platform for investigating in vivo whether ranavirus could disseminate to the brain. Our data show that the FV3 infection alters the BBB integrity, possibly mediated by an inflammatory response, which leads to viral dissemination into the central nervous system in X. laevis tadpole but not adult. Furthermore, our data suggest that the macrophages play a major role in viral dissemination by carrying the virus into the neural tissues. PMID:26931458

  7. Segmentation of center brains and optic lobes in 3D confocal images of adult fruit fly brains.

    PubMed

    Lam, Shing Chun Benny; Ruan, Zongcai; Zhao, Ting; Long, Fuhui; Jenett, Arnim; Simpson, Julie; Myers, Eugene W; Peng, Hanchuan

    2010-02-01

    Automatic alignment (registration) of 3D images of adult fruit fly brains is often influenced by the significant displacement of the relative locations of the two optic lobes (OLs) and the center brain (CB). In one of our ongoing efforts to produce a better image alignment pipeline of adult fruit fly brains, we consider separating CB and OLs and align them independently. This paper reports our automatic method to segregate CB and OLs, in particular under conditions where the signal to noise ratio (SNR) is low, the variation of the image intensity is big, and the relative displacement of OLs and CB is substantial. We design an algorithm to find a minimum-cost 3D surface in a 3D image stack to best separate an OL (of one side, either left or right) from CB. This surface is defined as an aggregation of the respective minimum-cost curves detected in each individual 2D image slice. Each curve is defined by a list of control points that best segregate OL and CB. To obtain the locations of these control points, we derive an energy function that includes an image energy term defined by local pixel intensities and two internal energy terms that constrain the curve's smoothness and length. Gradient descent method is used to optimize this energy function. To improve both the speed and robustness of the method, for each stack, the locations of optimized control points in a slice are taken as the initialization prior for the next slice. We have tested this approach on simulated and real 3D fly brain image stacks and demonstrated that this method can reasonably segregate OLs from CBs despite the aforementioned difficulties. PMID:19698789

  8. The functional organisation of glia in the adult brain of Drosophila and other insects

    PubMed Central

    Edwards, Tara N.; Meinertzhagen, Ian A.

    2010-01-01

    This review annotates and categorises the glia of adult Drosophila and other model insects and describes the developmental origins of these in the Drosophila optic lobe. The functions of glia in the adult vary depending upon their sub-type and location in the brain. The task of annotating glia is essentially complete only for the glia of the fly's lamina, which comprise: two types of surface glia - the pseudocartridge and fenestrated glia; two types of cortex glia - the distal and proximal satellite glia; and two types of neuropile glia - the epithelial and marginal glia. We advocate that the term subretinal glia, as used to refer to both pseudocartridge and fenestrated glia, be abandoned. Other neuropiles contain similar glial subtypes, but other than the antennal lobes these have not been described in detail. Surface glia form the blood brain barrier, regulating the flow of substances into and out of the nervous system, both for the brain as a whole and the optic neuropiles in particular. Cortex glia provide a second level of barrier, wrapping axon fascicles and isolating neuronal cell bodies both from neighbouring brain regions and from their underlying neuropiles. Neuropile glia can be generated in the adult and a subtype, ensheathing glia, are responsible for cleaning up cellular debris during Wallerian degeneration. Both the neuropile ensheathing and astrocyte-like glia may be involved in clearing neurotransmitters from the extracellular space, thus modifying the levels of histamine, glutamate and possibly dopamine at the synapse to ultimately affect behaviour. PMID:20109517

  9. Localization and regulation of PML bodies in the adult mouse brain.

    PubMed

    Hall, Małgorzata H; Magalska, Adriana; Malinowska, Monika; Ruszczycki, Błażej; Czaban, Iwona; Patel, Satyam; Ambrożek-Latecka, Magdalena; Zołocińska, Ewa; Broszkiewicz, Hanna; Parobczak, Kamil; Nair, Rajeevkumar R; Rylski, Marcin; Pawlak, Robert; Bramham, Clive R; Wilczyński, Grzegorz M

    2016-06-01

    PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic leukemia. In non-neuronal cells, PML is a principal component of characteristic nuclear bodies. In the brain, PML has been implicated in the control of embryonic neurogenesis, and in certain physiological and pathological phenomena in the adult brain. Yet, the cellular and subcellular localization of the PML protein in the brain, including its presence in the nuclear bodies, has not been investigated comprehensively. Because the formation of PML bodies appears to be a key aspect in the function of the PML protein, we investigated the presence of these structures and their anatomical distribution, throughout the adult mouse brain. We found that PML is broadly expressed across the gray matter, with the highest levels in the cerebral and cerebellar cortices. In the cerebral cortex PML is present exclusively in neurons, in which it forms well-defined nuclear inclusions containing SUMO-1, SUMO 2/3, but not Daxx. At the ultrastructural level, the appearance of neuronal PML bodies differs from the classic one, i.e., the solitary structure with more or less distinctive capsule. Rather, neuronal PML bodies have the form of small PML protein aggregates located in the close vicinity of chromatin threads. The number, size, and signal intensity of neuronal PML bodies are dynamically influenced by immobilization stress and seizures. Our study indicates that PML bodies are broadly involved in activity-dependent nuclear phenomena in adult neurons. PMID:25956166

  10. Calpain proteolysis of alpha II-spectrin in the normal adult human brain.

    PubMed

    Huh, G Y; Glantz, S B; Je, S; Morrow, J S; Kim, J H

    2001-12-01

    The proteolysis of alphaII-spectrin by calpain may be physiologically involved with synaptic remodeling, long-term potentiation, and memory formation. Calpain activation may also mediate neuronal apoptosis, responses to hypoxic insult, and excitotoxic injury. Surprisingly little is known of the activity of these calpain-mediated processes in the adult human brain. Using an antibody that specifically recognizes calpain-cleaved alphaII-spectrin, we have mapped the topographic distribution of the major alphaII-spectrin break-down product (alphaII-bdp1) in six adult brains examined post-mortem. All brains were from patients without evident neurological disease. Focally positive alphaII-bdp1 was consistently detected in the neuropil of the cortical gray matter, in occasional pyramidal neurons, and in rare reactive astrocytes in the cerebral cortex and hippocampus. Cerebellar Purkinje cells were more frequently, and more intensely, immunopositive. In all fields, staining was most intense in the soma and dendrites of neurons. There was no correlation of the frequency of positive cells with the postmortem interval or clinical condition. While these findings do not rigorously exclude contributions from postmortem calpain activation, they do suggest that a low-level of calpain processing of alphaII-spectrin is likely to be a constitutive process in the adult human brain. PMID:11720774

  11. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats

    PubMed Central

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R.; Tóth, Andrea E.; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A.

    2016-01-01

    Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and

  12. Light Scattering Properties Vary across Different Regions of the Adult Mouse Brain

    PubMed Central

    Stubblefield, Elizabeth A.; Felsen, Gidon

    2013-01-01

    Recently developed optogenetic tools provide powerful approaches to optically excite or inhibit neural activity. In a typical in-vivo experiment, light is delivered to deep nuclei via an implanted optical fiber. Light intensity attenuates with increasing distance from the fiber tip, determining the volume of tissue in which optogenetic proteins can successfully be activated. However, whether and how this volume of effective light intensity varies as a function of brain region or wavelength has not been systematically studied. The goal of this study was to measure and compare how light scatters in different areas of the mouse brain. We delivered different wavelengths of light via optical fibers to acute slices of mouse brainstem, midbrain and forebrain tissue. We measured light intensity as a function of distance from the fiber tip, and used the data to model the spread of light in specific regions of the mouse brain. We found substantial differences in effective attenuation coefficients among different brain areas, which lead to substantial differences in light intensity demands for optogenetic experiments. The use of light of different wavelengths additionally changes how light illuminates a given brain area. We created a brain atlas of effective attenuation coefficients of the adult mouse brain, and integrated our data into an application that can be used to estimate light scattering as well as required light intensity for optogenetic manipulation within a given volume of tissue. PMID:23874433

  13. Structural and Functional Rich Club Organization of the Brain in Children and Adults

    PubMed Central

    Grayson, David S.; Ray, Siddharth; Carpenter, Samuel; Iyer, Swathi; Dias, Taciana G. Costa; Stevens, Corinne; Nigg, Joel T.; Fair, Damien A.

    2014-01-01

    Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain’s white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain’s major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism. PMID:24505468

  14. Nuclear receptors of the honey bee: annotation and expression in the adult brain

    PubMed Central

    Velarde, Rodrigo A; Robinson, Gene E; Fahrbach, Susan E

    2006-01-01

    The Drosophila genome encodes 18 canonical nuclear receptors. All of the Drosophila nuclear receptors are here shown to be present in the genome of the honey bee (Apis mellifera). Given that the time since divergence of the Drosophila and Apis lineages is measured in hundreds of millions of years, the identification of matched orthologous nuclear receptors in the two genomes reveals the fundamental set of nuclear receptors required to ‘make’ an endopterygote insect. The single novelty is the presence in the A. mellifera genome of a third insect gene similar to vertebrate photoreceptor-specific nuclear receptor (PNR). Phylogenetic analysis indicates that this novel gene, which we have named AmPNR-like, is a new member of the NR2 subfamily not found in the Drosophila or human genomes. This gene is expressed in the developing compound eye of the honey bee. Like their vertebrate counterparts, arthropod nuclear receptors play key roles in embryonic and postembryonic development. Studies in Drosophila have focused primarily on the role of these transcription factors in embryogenesis and metamorphosis. Examination of an expressed sequence tag library developed from the adult bee brain and analysis of transcript expression in brain using in situ hybridization and quantitative RT-PCR revealed that several members of the nuclear receptor family (AmSVP, AmUSP, AmERR, AmHr46, AmFtz-F1, and AmHnf-4) are expressed in the brain of the adult bee. Further analysis of the expression of AmUSP and AmSVP in the mushroom bodies, the major insect brain centre for learning and memory, revealed changes in transcript abundance and, in the case of AmUSP, changes in transcript localization, during the development of foraging behaviour in the adult. Study of the honey bee therefore provides a model for understanding nuclear receptor function in the adult brain. PMID:17069634

  15. BRAIN EXPRESSION AND SONG REGULATION OF THE CHOLECYSTOKININ GENE IN THE ZEBRA FINCH (TAENIOPYGIA GUTTATA)

    PubMed Central

    Lovell, Peter V.; Mello, Claudio V.

    2010-01-01

    The gene encoding cholecystokinin (Cck) is abundantly expressed in the mammalian brain and has been associated with such functions as feeding termination and satiety, locomotion and self-stimulation, the modulation of anxiety-like behaviors, and learning and memory. Here we describe the brain expression and song regulation of Cck in the brain of the adult male zebra finch (Taeniopygia guttata), a songbird species. Using in situ hybridization, we demonstrate that Cck is highly expressed in several discrete brain regions, most prominently the caudal-most portion of the hippocampal formation, the caudodorsal nidopallial shelf and the caudomedial nidopallium (NCM), the core or shell regions of dorsal thalamic nuclei, dopaminergic cell groups in the mesencephalon and pons, the principal nucleus of the trigeminal nerve, and the dorsal raphe. Cck was largely absent in song control system, a group of nuclei required for vocal learning and song production in songbirds, though sparse labeling was detected throughout the striatum, including song nucleus area X. We also show that levels of Cck mRNA and the number of labeled cells increase in the NCM of males and females following auditory stimulation with conspecific song. Double labeling further reveals that the majority of Cck cells, excluding those in the reticular nucleus of the thalamus, are non-GABAergic. Together, these data provide the first comprehensive characterization of Cck expression in a songbird, and suggest a possible involvement of Cck regulation in important aspects of birdsong biology, such as perceptual processing, auditory memorization and/or vocal-motor control of song production. PMID:21165972

  16. Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

    SciTech Connect

    Shahbazian, F.M.

    1985-01-01

    Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of (/sup 14/C)valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements.

  17. Normative data for subcortical regional volumes over the lifetime of the adult human brain.

    PubMed

    Potvin, Olivier; Mouiha, Abderazzak; Dieumegarde, Louis; Duchesne, Simon

    2016-08-15

    Normative data for volumetric estimates of brain structures are necessary to adequately assess brain volume alterations in individuals with suspected neurological or psychiatric conditions. Although many studies have described age and sex effects in healthy individuals for brain morphometry assessed via magnetic resonance imaging, proper normative values allowing to quantify potential brain abnormalities are needed. We developed norms for volumetric estimates of subcortical brain regions based on cross-sectional magnetic resonance scans from 2790 healthy individuals aged 18 to 94years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer, a widely used and freely available automated segmentation software. Models predicting subcortical regional volumes of each hemisphere were produced including age, sex, estimated total intracranial volume (eTIV), scanner manufacturer, magnetic field strength, and interactions as predictors. The mean explained variance by the models was 48%. For most regions, age, sex and eTIV predicted most of the explained variance while manufacturer, magnetic field strength and interactions predicted a limited amount. Estimates of the expected volumes of an individual based on its characteristics and the scanner characteristics can be obtained using derived formulas. For a new individual, significance test for volume abnormality, effect size and estimated percentage of the normative population with a smaller volume can be obtained. Normative values were validated in independent samples of healthy adults and in adults with Alzheimer's disease and schizophrenia. PMID:27165761

  18. Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

    PubMed

    Priller, Josef

    2003-08-01

    While the brain has traditionally been considered a rather secluded site, recent studies suggest that adult bone marrow (BM)-derived stem cells can generate glia and neurons in rodents and humans. Macrophages and microglia are the first to appear in the murine brain after transplantation of genetically marked BM cells. Within weeks after transplantation, some authors have found astrocytes and cells expressing neuronal antigens. We detected cerebellar Purkinje neurons and interneurons, such as basket cells, expressing the green fluorescent protein (GFP) 10-15 months after transplantation of GFP-labeled BM cells. The results push the boundaries of our classic view of lineage restriction. PMID:12898276

  19. Brain metabolism and memory in age differentiated healthy adults

    SciTech Connect

    Riege, W.H.; Metter, E.J.; Kuhl, D.E.; Phelps, M.E.

    1984-01-01

    The (F-18)-fluorodeoxyglucose (FDG) scan method with positron emission tomography was used to determine age differences in factors underlying both the performances on 18 multivariate memory tests and the rates of cerebral glucose utilization in 9 left and 9 right hemispheric regions of 23 healthy adults in the age range of 27-78 years. Young persons below age 42 had higher scores than middle-aged (age 48-65 yrs) or old (age 66-78 yrs) persons on two of seven factors, reflecting memory for sequences of words or events together with metabolic indices of Broca's (and its mirror region) and Thalamic areas. Reliable correlations (critical r = 0.48, p<0.02) indicated that persons with high Superior Frontal and low Caudate-Thalamic metabolic measures were the same who performed well in tests of memory for sentences, story, designs, and complex patterns; while metabolic indices of Occipital and Posterior Temporal regions were correlated with the decision criteria adopted in testing. The mean metabolic ratio (b = -0.033, F = 5.47, p<0.03) and those of bilateral Broca's regions (b = -0.002, F = 13.65, p<0.001) significantly declined with age. The functional interrelation of frontal-subcortical metabolic ratios with memory processing was more prominent in younger persons under study and implicates decreasing thalamo-frontal interaction with age.

  20. Pediatric Cancers and Brain Tumors in Adolescents and Young Adults.

    PubMed

    McCabe, Martin G; Valteau-Couanet, Dominique

    2016-01-01

    Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood. These tumors are less well understood, usually not managed according to standardized protocols and rarely included in clinical trials. Survival outcomes are generally poorer than their childhood equivalents. We present here a summary of the published literature on embryonal tumors that present ectopically during adolescence and adulthood. We show that for some tumors protocol-driven treatment, supported by accurate and complete diagnostics and staging, can result in equivalent outcomes to those seen during childhood. We make the case that clinical trial eligibility criteria should be disease-based rather than age-based, and support improvements in dialogue between children's and adults' cancer clinicians to improve outcomes for these rare tumors. PMID:27595358

  1. Rehabilitation for Adults with Traumatic Brain Injury: Where Will We Be Clinically in 2026?

    PubMed

    Turkstra, Lyn S

    2016-08-01

    In 10 years, there might be fewer adults who need rehabilitation after traumatic brain injury because of advances in injury prevention and very early treatment. For adults who do need rehabilitation, assessment might include biosensor recordings in their everyday communication contexts, and home practice might be delivered by a robot that can be programmed to mimic target characteristics of human behavior. These advances in science and technology will enhance rehabilitation, but it will always be our responsibility as speech-language pathologists to advocate for our patients and clients and support them in achieving the best possible quality of communication life. PMID:27232097

  2. The brain and the braincase: a spatial analysis on the midsagittal profile in adult humans.

    PubMed

    Bruner, Emiliano; Amano, Hideki; de la Cuétara, José Manuel; Ogihara, Naomichi

    2015-09-01

    The spatial relationships between brain and braincase represent a major topic in surgery and evolutionary neuroanatomy. In paleoneurology, neurocranial landmarks are often used as references for brain areas. In this study, we analyze the variation and covariation of midsagittal brain and skull coordinates in a sample of adult modern humans in order to demonstrate spatial associations between hard and soft tissues. The correlation between parietal lobe size and parietal bone size is very low, and there is a marked individual variation. The distances between lobes and bones are partially influenced by the dimensions of the parietal lobes. The main pattern of morphological variability among individuals, associated with the size of the precuneus, apparently does not influence the position of the neurocranial sutures. Therefore, variations in precuneal size modify the distance between the paracentral lobule and bregma, and between the parietal lobe and lambda. Hence, the relative position of the cranial and cerebral landmarks can change as a function of the parietal dimensions. The slight correlation and covariation among these elements suggests a limited degree of spatial integration between soft and hard tissues. Therefore, although the brain influences the cranial size and shape during morphogenesis, the specific position of the cerebral components is sensitive to multiple effects and local factors, without a strict correspondence with the bone landmarks. This absence of correspondent change between brain and skull boundaries suggests caution when making inferences about the brain areas from the position of the cranial sutures. The fact that spatial relationships between cranial and brain areas may vary according to brain proportions must be considered in paleoneurology, when brain anatomy is inferred from cranial evidence. PMID:26200138

  3. Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults

    PubMed Central

    Voss, Michelle W.; Prakash, Ruchika S.; Erickson, Kirk I.; Basak, Chandramallika; Chaddock, Laura; Kim, Jennifer S.; Alves, Heloisa; Heo, Susie; Szabo, Amanda N.; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L.; Gothe, Neha; Olson, Erin A.; McAuley, Edward; Kramer, Arthur F.

    2010-01-01

    Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction. PMID:20890449

  4. Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

    PubMed Central

    2012-01-01

    Background Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted. PMID:22695063

  5. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    PubMed

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration. PMID:25977550

  6. Environmental Impact on Direct Neuronal Reprogramming In Vivo in the Adult Brain

    PubMed Central

    López-Juárez, Alejandro; Howard, Jennifer; Sakthivel, Bhuvaneswari; Aronow, Bruce; Campbell, Kenneth; Nakafuku, Masato

    2013-01-01

    Direct reprogramming of non-neuronal cells to generate new neurons is a promising approach to repair damaged brains. Impact of the in vivo environment on neuronal reprogramming, however, is poorly understood. Here we show that regional differences and injury conditions have significant influence on the efficacy of reprogramming and subsequent survival of newly generated neurons in the adult rodent brain. A combination of local exposure to growth factors and retrovirus-mediated overexpression of the neurogenic transcription factor Neurogenin2 (Neurog2) can induce new neurons from non-neuronal cells in the adult neocortex and striatum where neuronal turnover is otherwise very limited. These two regions respond to growth factors and Neurog2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo. PMID:23974433

  7. Sex differences and rapid estrogen signaling: a look at songbird audition

    PubMed Central

    Krentzel, Amanda A.; Remage-Healey, Luke

    2015-01-01

    The actions of estrogens have been associated with brain differentiation and sexual dimorphism in a wide range of vertebrates. Here we consider the actions of brain-derived ‘neuroestrogens’ in the forebrain and the accompanying differences and similarities observed between males and females in a variety of species. We summarize recent evidence showing that baseline and fluctuating levels of neuroestrogens within the auditory forebrain of male and female zebra finches are largely similar, and that neuroestrogens enhance auditory representations in both sexes. With a comparative perspective we review evidence that non-genomic mechanisms of neuroestrogen actions are sexually differentiated, and we propose a working model for nonclassical estrogen signaling via the MAPK intracellular signaling cascade in the songbird auditory forebrain that is informed by the way sex differences may be compensated. This view may lead to a more comprehensive understanding of how sex influences estradiol-dependent modulation of sensorimotor representations. PMID:25637753

  8. Brain Training Game Boosts Executive Functions, Working Memory and Processing Speed in the Young Adults: A Randomized Controlled Trial

    PubMed Central

    Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

    2013-01-01

    Background Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. Methods We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Results and Discussion Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Conclusions Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. Trial

  9. Applications of hybrid diffuse optics for clinical management of adults after brain injury

    NASA Astrophysics Data System (ADS)

    Kim, Meeri Nam

    Information about cerebral blood flow (CBF) is valuable for clinical management of patients after severe brain injury. Unfortunately, current modalities for monitoring brain are often limited by hurdles that include high cost, low throughput, exposure to ionizing radiation, probe invasiveness, and increased risk to critically ill patients when transportation out of their room or unit is required. A further limitation of current technologies is an inability to provide continuous bedside measurements that are often desirable for unstable patients. Here we explore the clinical utility of diffuse correlation spectroscopy (DCS) as an alternative approach for bedside CBF monitoring. DCS uses the rapid intensity fluctuations of near-infrared light to derive a continuous measure of changes in blood flow without ionizing radiation or invasive probing. Concurrently, we employ another optical technique, called diffuse optical spectroscopy (DOS), to derive changes in cerebral oxyhemoglobin ( HbO2) and deoxyhemoglobin (Hb) concentrations. Our clinical studies integrate DCS with DOS into a single hybrid instrument that simultaneously monitors CBF and HbO2/Hb in the injured adult brain. The first parts of this dissertation present the motivations for monitoring blood flow in injured brain, as well as the theory underlying diffuse optics technology. The next section elaborates on details of the hybrid instrumentation. The final chapters describe four human subject studies carried out with these methods. Each of these studies investigates an aspect of the potential of the hybrid monitor in clinical applications involving adult brain. The studies include: (1) validation of DCS-measured CBF against xenon-enhanced computed tomography in brain-injured adults; (2) a study of the effects of age and gender on posture-change-induced CBF variation in healthy subjects; (3) a study of the efficacy of DCS/DOS for monitoring neurocritical care patients during various medical interventions such

  10. Regulation of netrin-1 receptors by amphetamine in the adult brain.

    PubMed

    Yetnikoff, L; Labelle-Dumais, C; Flores, C

    2007-12-19

    Netrin-1 is a guidance cue molecule fundamental to the organization of neuronal connectivity during development. Netrin-1 and its receptors, deleted in colorectal cancer (DCC) and UNC-5 homologues (UNC-5), continue to be expressed in the adult brain, although neither their function nor the kinds of events that activate their expression are known. Two lines of evidence suggest a role for netrin-1 in amphetamine-induced dopamine plasticity in the adult. First, DCC is highly expressed by adult dopamine neurons. Second, adult mice with reduced DCC levels do not develop amphetamine-induced behavioral sensitization. To explore the role of netrin-1 in amphetamine-induced plasticity, we examined the effects of sensitizing treatment regimens of amphetamine on DCC and/or UNC-5 protein expression in the adult rat. These treatments produced striking and enduring increases in DCC and UNC-5 expression in the cell body, but not terminal regions, of the mesocorticolimbic dopamine system. Notably, neuroadaptations in the cell body region of mesocorticolimbic dopamine neurons underlie the development of sensitization to the effects of amphetamine. Furthermore, these localized amphetamine-induced changes were prevented by co-treatment with an N-methyl-d-aspartate receptor antagonist, a treatment known to block the development of amphetamine-induced sensitization of behavioral activation, dopamine release and motivated behavior. Using immunohistochemistry, we showed that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic dopamine neurons. These results provide the first evidence that repeated exposure to a stimulant drug such as amphetamine affects netrin-1 receptor expression in the adult brain. Taken together, our findings suggest that changes in netrin-1 receptor expression may play a role in the lasting effects of exposure to amphetamine and other stimulant drugs. PMID:17996376

  11. REGULATION OF NETRIN-1 RECEPTORS BY AMPHETAMINE IN THE ADULT BRAIN

    PubMed Central

    YETNIKOFF, L.; LABELLE-DUMAIS, C.; FLORES, C.

    2016-01-01

    Netrin-1 is a guidance cue molecule fundamental to the organization of neuronal connectivity during development. Netrin-1 and its receptors, deleted in colorectal cancer (DCC) and UNC-5 homologues (UNC-5), continue to be expressed in the adult brain, although neither their function nor the kinds of events that activate their expression are known. Two lines of evidence suggest a role for netrin-1 in amphetamine-induced dopamine plasticity in the adult. First, DCC is highly expressed by adult dopamine neurons. Second, adult mice with reduced DCC levels do not develop amphetamine-induced behavioral sensitization. To explore the role of netrin-1 in amphetamine-induced plasticity, we examined the effects of sensitizing treatment regimens of amphetamine on DCC and/or UNC-5 protein expression in the adult rat. These treatments produced striking and enduring increases in DCC and UNC-5 expression in the cell body, but not terminal regions, of the mesocorticolimbic dopamine system. Notably, neuroadaptations in the cell body region of mesocorticolimbic dopamine neurons underlie the development of sensitization to the effects of amphetamine. Furthermore, these localized amphetamine-induced changes were prevented by co-treatment with an N-methyl-D-aspartate receptor antagonist, a treatment known to block the development of amphetamine-induced sensitization of behavioral activation, dopamine release and motivated behavior. Using immunohistochemistry, we showed that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic dopamine neurons. These results provide the first evidence that repeated exposure to a stimulant drug such as amphetamine affects netrin-1 receptor expression in the adult brain. Taken together, our findings suggest that changes in netrin-1 receptor expression may play a role in the lasting effects of exposure to amphetamine and other stimulant drugs. PMID:17996376

  12. A METHODOLOGY FOR ANALYZING CURVATURE IN THE DEVELOPING BRAIN FROM PRETERM TO ADULT

    PubMed Central

    PIENAAR, R.; FISCHL, B.; CAVINESS, V.; MAKRIS, N.; GRANT, P. E.

    2009-01-01

    The character and timing of gyral development is one manifestation of the complex orchestration of human brain development. The ability to quantify these changes would not only allow for deeper understanding of cortical development, but also conceivably allow for improved detection of pathologies. This paper describes a FreeSurfer based image-processing analysis “pipeline” or methodology that inputs an MRI volume, corrects possible contrast defects, creates surface reconstructions, and outputs various curvature-based function analyses. A technique of performing neonate reconstructions using FreeSurfer, which has not been possible previously due to inverted image contrast in pre-myelinated brains, is described. Once surfaces are reconstructed, the analysis component of the pipeline incorporates several surface-based curvature functions found in literature (principle curvatures, Gaussian, mean curvature, “curvedness”, and Willmore Bending Energy). We consider the problem of analyzing curvatures from different sized brains by introducing a Gaussian-curvature based variable-radius filter. Segmented volume data is also analyzed for folding measures: a gyral folding index (gyrification-white index GWI), and a gray-white matter junction folding index (WMF). A very simple curvature-based classifier is proposed that has the potential to discriminate between certain classes of subjects. We also present preliminary results of this curvature analysis pipeline on nine neonate subjects (30.4 weeks through 40.3 weeks Corrected Gestational Age), 3 children (2, 3, and 7 years) and 3 adults (33, 37, and 39 years). Initial results demonstrate that curvature measures and functions across our subjects peaked at term, with a gradual decline through early childhood and further decline continuing through to adults. We can also discriminate older neonates, children, and adults based on curvature analysis. Using a variable radius Gaussian-curvature filter, we also observed that the

  13. Eph receptor and ephrin signaling in developing and adult brain of the honeybee (Apis mellifera).

    PubMed

    Vidovic, Maria; Nighorn, Alan; Koblar, Simon; Maleszka, Ryszard

    2007-02-01

    Roles for Eph receptor tyrosine kinase and ephrin signaling in vertebrate brain development are well established. Their involvement in the modulation of mammalian synaptic structure and physiology is also emerging. However, less is known of their effects on brain development and their function in adult invertebrate nervous systems. Here, we report on the characterization of Eph receptor and ephrin orthologs in the honeybee, Apis mellifera (Am), and their role in learning and memory. In situ hybridization for mRNA expression showed a uniform distribution of expression of both genes across the developing pupal and adult brain. However, in situ labeling with Fc fusion proteins indicated that the AmEphR and Amephrin proteins were differentially localized to cell body regions in the mushroom bodies and the developing neuropiles of the antennal and optic lobes. In adults, AmEphR protein was localized to regions of synaptic contacts in optic lobes, in the glomeruli of antennal lobes, and in the medial lobe of the mushroom body. The latter two regions are involved in olfactory learning and memory in the honeybee. Injections of EphR-Fc and ephrin-Fc proteins into the brains of adult bees, 1 h before olfactory conditioning of the proboscis extension reflex, significantly reduced memory 24 h later. Experimental amnesia in the group injected with ephrin-Fc was apparent 1 h post-training. Experimental amnesia was also induced by post-training injections with ephrin-Fc suggesting a role in recall. This is the first demonstration that Eph molecules function to regulate the formation of memory in insects. PMID:17443785

  14. Eph Receptor and Ephrin Signaling in Developing and Adult Brain of the Honeybee (Apis mellifera)

    PubMed Central

    Vidovic, Maria; Nighorn, Alan; Koblar, Simon; Maleszka, Ryszard

    2007-01-01

    Roles for Eph receptor tyrosine kinase and ephrin signaling in vertebrate brain development are well established. Their involvement in the modulation of mammalian synaptic structure and physiology is also emerging. However, less is known of their effects on brain development and their function in adult invertebrate nervous systems. Here, we report on the characterization of Eph receptor and ephrin orthologs in the honeybee, Apis mellifera (Am), and their role in learning and memory. In situ hybridization for mRNA expression showed a uniform distribution of expression of both genes across the developing pupal and adult brain. However, in situ labeling with Fc fusion proteins indicated that the AmEphR and Amephrin proteins were differentially localized to cell body regions in the mushroom bodies and the developing neuropiles of the antennal and optic lobes. In adults, AmEphR protein was localized to regions of synaptic contacts in optic lobes, in the glomeruli of antennal lobes, and in the medial lobe of the mushroom body. The latter two regions are involved in olfactory learning and memory in the honeybee. Injections of EphR-Fc and ephrin-Fc proteins into the brains of adult bees, 1 h before olfactory conditioning of the proboscis extension reflex, sig-nificantly reduced memory 24 h later. Experimental amnesia in the group injected with ephrin-Fc was apparent 1 h post-training. Experimental amnesia was also induced by post-training injections with ephrin-Fc suggesting a role in recall. This is the first demonstration that Eph molecules function to regulate the formation of memory in insects. PMID:17443785

  15. Graph Theory Analysis of Functional Brain Networks and Mobility Disability in Older Adults

    PubMed Central

    Burdette, Jonathan H.; Morgan, Ashley R.; Williamson, Jeff D.; Kritchevsky, Stephen B.; Laurienti, Paul J.

    2014-01-01

    Background. The brain’s structural integrity is associated with mobility function in older adults. Changes in function may be evident earlier than changes in structure and may be more directly related to mobility. Therefore, we assessed whether functional brain networks varied with mobility function in older adults. Methods. Short Physical Performance Battery (SPPB) and resting state functional magnetic resonance imaging were collected on 24 young (mean age = 26.4±5.1) and 48 older (mean age = 72.04±5.1) participants. Older participants were divided into three groups by SPPB score: Low SPPB (score = 7–9), Mid SPPB (score = 10), High SPPB (score = 11–12).Graph theory–based methods were used to characterize and compare brain network organization. Results. Connectivity in the somatomotor cortex distinguished between groups based on SPPB score. The community structure of the somatomotor cortex was significantly less consistent in the Low SPPB group (mean = 0.097±0.05) compared with Young (mean = 0.163±0.09, p = .03) SPPB group. Striking differences were evident in second-order connections between somatomotor cortex and superior temporal gyrus and insula that reached statistical significance. The Low SPPB group (mean = 140.87±109.30) had a significantly higher number of connections than Young (mean = 45.05±33.79, p = .0003) or High (mean = 49.61±35.31, p = .002) SPPB group. Conclusions. Older adults with poorer mobility function exhibited reduced consistency of somatomotor community structure and a greater number of secondary connections with vestibular and multisensory regions of the brain. Further study is needed to fully interpret these effects, but analysis of functional brain networks adds new insights to the contribution of the brain to mobility. PMID:24717331

  16. A customizable 3-dimensional digital atlas of the canary brain in multiple modalities.

    PubMed

    Vellema, Michiel; Verschueren, Jacob; Van Meir, Vincent; Van der Linden, Annemie

    2011-07-15

    Songbirds are well known for their ability to learn their vocalizations by imitating conspecific adults. This uncommon skill has led to many studies examining the behavioral and neurobiological processes involved in vocal learning. Canaries display a variable, seasonally dependent, vocal behavior throughout their lives. This trait makes this bird species particularly valuable to study the functional relationship between the continued plasticity in the singing behavior and alterations in the anatomy and physiology of the brain. In order to optimally interpret these types of studies, a detailed understanding of the brain anatomy is essential. Because traditional 2-dimensional brain atlases are limited in the information they can provide about the anatomy of the brain, here we present a 3-dimensional MRI-based atlas of the canary brain. Using multiple imaging protocols we were able to maximize the number of detectable brain regions, including most of the areas involved in song perception, learning, and production. The brain atlas can readily be used to determine the stereotactic location of delineated brain areas at any desirable head angle. Alternatively the brain data can be used to determine the ideal orientation of the brain for stereotactic injections, electrophysiological recordings, and brain sectioning. The 3-dimensional canary brain atlas presented here is freely available and is easily adaptable to support many types of neurobiological studies, including anatomical, electrophysiological, histological, explant, and tracer studies. PMID:21565273

  17. Neuronal Organization of the Brain in the Adult Amphioxus (Branchiostoma lanceolatum): A Study With Acetylated Tubulin Immunohistochemistry.

    PubMed

    Castro, Antonio; Becerra, Manuela; Manso, María Jesús; Anadón, Ramón

    2015-10-15

    Amphioxus (Cephalochordata) belongs to the most basal extant chordates, and knowledge of their brain organization appears to be key to deciphering the early stages of evolution of vertebrate brains. Most comprehensive studies of the organization of the central nervous system of adult amphioxus have investigated the spinal cord. Some brain populations have been characterized via neurochemistry and electron microscopy, and the overall cytoarchitecture of the brain was studied by Ekhart et al. (2003; J. Comp. Neurol. 466:319-330) with general staining methods and retrograde transport from the spinal cord. Here, the cytoarchitecture of the brain of adult amphioxus Branchiostoma lanceolatum was reinvestigated by using acetylated tubulin immunohistochemistry, which specifically stains neurons and fibers, in combination with some ancillary methods. This method allowed reproducible staining and mapping of types of neuron, mostly in brain regions caudal to the entrance level of nerve 2, and its comparison with spinal cord populations. The brain populations studied and discussed in detail were the Retzius bipolar cells, lamellate cells, Joseph cells, various types of translumenal cells, somatic motoneurons, Rohde nucleus cells, small ventral multipolar neurons, and Edinger cells. These observations expand our knowledge of the distribution of cell types and provide additional data on the number of cells and the axonal tracts and commissural regions of the adult amphioxus brain. The results of this comprehensive study provide a framework for comparison of complex adult populations with the early brain neuronal populations revealed in developmental studies of the amphioxus. PMID:25846052

  18. Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification in Older Adults: Preliminary Results.

    PubMed

    Szymkowicz, Sarah M; Persson, Jonas; Lin, Tian; Fischer, Håkan; Ebner, Natalie C

    2016-01-01

    Quick correct identification of facial emotions is highly relevant for successful social interactions. Research suggests that older, compared to young, adults experience increased difficulty with face and emotion processing skills. While functional neuroimaging studies suggest age differences in neural processing of faces and emotions, evidence about age-associated structural brain changes and their involvement in face and emotion processing is scarce. Using structural magnetic resonance imaging (MRI), this study investigated the extent to which volumes of frontal and temporal brain structures were related to reaction time in accurate identification of facial emotions in 30 young and 30 older adults. Volumetric segmentation was performed using FreeSurfer and gray matter volumes from frontal and temporal regions were extracted. Analysis of covariances (ANCOVAs) models with response time (RT) as the dependent variable and age group and regional volume, and their interaction, as independent variables were conducted, controlling for total intracranial volume (ICV). Results indicated that, in older adults, larger hippocampal volumes were associated with faster correct facial emotion identification. These preliminary observations suggest that greater volume in brain regions associated with face and emotion processing contributes to improved facial emotion identification performance in aging. PMID:27610082

  19. ChIP-Seq analysis of the adult male mouse brain after developmental exposure to arsenic.

    PubMed

    Tyler, Christina R; Weber, Jessica A; Labrecque, Matthew; Hessinger, Justin M; Edwards, Jeremy S; Allan, Andrea M

    2015-12-01

    Exposure to the common environmental contaminant arsenic impacts the epigenetic landscape, including DNA methylation and histone modifications, of several cell types. Developmental arsenic exposure (DAE) increases acetylation and methylation of histone proteins and the protein expression of several chromatin-modifying enzymes in the dentate gyrus (DG) subregion of the adult male mouse brain [26]. To complement and support these data, ChIP-Seq analysis of DNA associated with trimethylation of histone 3 lysine 4 (H3K4me3) derived from the adult male DG after DAE was performed. DAE induced differential H3K4me3 enrichment on genes in pathways associated with cellular development and growth, cell death and survival, and neurological disorders, particularly as they relate to cancer, in the adult male brain. Comparison of H3K4me3 enrichment in controls revealed mechanisms that are potentially lacking in arsenic-exposed animals, including neurotransmission, neuronal growth and development, hormonal regulation, protein synthesis, and cellular homeostasis. New pathways impacted by arsenic include cytoskeleton organization, cell signaling, and potential disruption of immune function and warrant further investigation using this DAE paradigm in the mouse brain. PMID:26543888

  20. Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification in Older Adults: Preliminary Results

    PubMed Central

    Szymkowicz, Sarah M.; Persson, Jonas; Lin, Tian; Fischer, Håkan; Ebner, Natalie C.

    2016-01-01

    Quick correct identification of facial emotions is highly relevant for successful social interactions. Research suggests that older, compared to young, adults experience increased difficulty with face and emotion processing skills. While functional neuroimaging studies suggest age differences in neural processing of faces and emotions, evidence about age-associated structural brain changes and their involvement in face and emotion processing is scarce. Using structural magnetic resonance imaging (MRI), this study investigated the extent to which volumes of frontal and temporal brain structures were related to reaction time in accurate identification of facial emotions in 30 young and 30 older adults. Volumetric segmentation was performed using FreeSurfer and gray matter volumes from frontal and temporal regions were extracted. Analysis of covariances (ANCOVAs) models with response time (RT) as the dependent variable and age group and regional volume, and their interaction, as independent variables were conducted, controlling for total intracranial volume (ICV). Results indicated that, in older adults, larger hippocampal volumes were associated with faster correct facial emotion identification. These preliminary observations suggest that greater volume in brain regions associated with face and emotion processing contributes to improved facial emotion identification performance in aging. PMID:27610082

  1. Reawakening the sleeping beauty in the adult brain: neurogenesis from parenchymal glia.

    PubMed

    Péron, Sophie; Berninger, Benedikt

    2015-10-01

    Life-long neurogenesis is highly restricted to specialized niches in the adult mammalian brain and therefore the brain's capacity for spontaneous regeneration is extremely limited. However, recent work has demonstrated that under certain circumstances parenchymal astrocytes and NG2 glia can generate neuronal progeny. In the striatum, stroke or excitotoxic lesions can reawaken in astrocytes a latent neurogenic program resulting in the genesis of new neurons. By contrast, in brain areas that fail to mount a neurogenic response following injury, such as the cerebral cortex, forced expression of neurogenic reprogramming factors can lineage convert local glia into induced neurons. Yet, injury-induced and reprogramming-induced neurogenesis exhibit intriguing commonalities, suggesting that they may converge on similar mechanisms. PMID:26296150

  2. Notch Receptor Expression in Neurogenic Regions of the Adult Zebrafish Brain

    PubMed Central

    de Oliveira-Carlos, Vanessa; Ganz, Julia; Hans, Stefan; Kaslin, Jan; Brand, Michael

    2013-01-01

    The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches. PMID:24039926

  3. Brain morphological changes in adolescent and adult patients with anorexia nervosa.

    PubMed

    Seitz, J; Herpertz-Dahlmann, B; Konrad, K

    2016-08-01

    Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (-8.4 vs -3.1 %), the difference in WM (-4.0 vs -2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5-8 years of remission, GM and WM were no longer significantly reduced in adults (GM -0.4 %, WM -0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains. PMID:27188331

  4. Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum

    PubMed Central

    Olivera-Pasilio, Valentina; Peterson, Daniel A.; Castelló, María E.

    2014-01-01

    Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24 h) and long (30 day) chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers), sparse slow cycling (potentially stem) cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones. PMID:25249943

  5. Region-Specific Neural Corticosterone Patterns Differ From Plasma in a Male Songbird

    PubMed Central

    Comito, D.; Kosarussavadi, S.; Schlinger, B. A.

    2014-01-01

    The adrenal hormone corticosterone (CORT) acts on brain to mediate physiology and behavior. In songbirds, behavioral effects of CORT vary across species, environmental conditions, and life history stage, with several mechanisms proposed to account for these divergent results. Although blood CORT levels are well characterized, few studies measure CORT within the brain itself. Here we used in vivo microdialysis to measure CORT in two regions of the zebra finch brain, the hippocampus (HP) and caudal nidopallium (cNp). Our results show that we can successfully measure physiological levels of CORT in brain within 15- to 30-minute intervals of dialysate collection. Moreover, we found that levels in the cNp were generally lower than levels in the HP. Surprisingly, whereas plasma CORT levels increased in response to a standard stressor, no stress-induced surge was detected in the HP or cNp. In addition, although a diel CORT rhythm was observed in plasma, the rhythm in brain was attenuated and only observed when levels were integrated over a 4-hour time period. Regional differences in brain CORT levels were reflected in local mRNA expression levels of the CORT-inactivating enzyme 11β-hydroxysteroid dehydrogenase type 2 with levels elevated in the cNp relative to the HP. Region-specific CORT metabolism may therefore play a role in buffering the brain from CORT fluctuations. PMID:24914945

  6. Brain-expressed imprinted genes and adult behaviour: the example of Nesp and Grb10.

    PubMed

    Dent, Claire L; Isles, Anthony R

    2014-02-01

    Imprinted genes are defined by their parent-of-origin-specific monoallelic expression. Although the epigenetic mechanisms regulating imprinted gene expression have been widely studied, their functional importance is still unclear. Imprinted genes are associated with a number of physiologies, including placental function and foetal growth, energy homeostasis, and brain and behaviour. This review focuses on genomic imprinting in the brain and on two imprinted genes in particular, Nesp and paternal Grb10, which, when manipulated in animals, have been shown to influence adult behaviour. These two genes are of particular interest as they are expressed in discrete and overlapping neural regions, recognised as key "imprinting hot spots" in the brain. Furthermore, these two genes do not appear to influence placental function and/or maternal provisioning of offspring. Consequently, by understanding their behavioural function we may begin to shed light on the evolutionary significance of imprinted genes in the adult brain, independent of the recognised role in maternal care. In addition, we discuss the potential future directions of research investigating the function of these two genes and the behavioural role of imprinted genes more generally. PMID:23974804

  7. Brain changes in older adults at very low risk for Alzheimer's disease.

    PubMed

    Fjell, Anders M; McEvoy, Linda; Holland, Dominic; Dale, Anders M; Walhovd, Kristine B

    2013-05-01

    Alzheimer's disease (AD) has a slow onset, so it is challenging to distinguish brain changes in healthy elderly persons from incipient AD. One-year brain changes with a distinct frontotemporal pattern have been shown in older adults. However, it is not clear to what extent these changes may have been affected by undetected, early AD. To address this, we estimated 1-year atrophy by magnetic resonance imaging (MRI) in 132 healthy elderly persons who had remained free of diagnosed mild cognitive impairment or AD for at least 3 years. We found significant volumetric reductions throughout the brain. The sample was further divided into low-risk groups based on clinical, biomarker, genetic, or cognitive criteria. Although sample sizes varied, significant reductions were observed in all groups, with rates and topographical distribution of atrophy comparable to that of the full sample. Volume reductions were especially pronounced in the default mode network, closely matching the previously described frontotemporal pattern of changes in healthy aging. Atrophy in the hippocampus predicted change in memory, with no additional default mode network contributions. In conclusion, reductions in regional brain volumes can be detected over the course of 1 year even in older adults who are unlikely to be in a presymptomatic stage of AD. PMID:23658162

  8. Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas

    PubMed Central

    Aboody, Karen S.; Brown, Alice; Rainov, Nikolai G.; Bower, Kate A.; Liu, Shaoxiong; Yang, Wendy; Small, Juan E.; Herrlinger, Ulrich; Ourednik, Vaclav; Black, Peter McL.; Breakefield, Xandra O.; Snyder, Evan Y.

    2000-01-01

    One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and migrate widely into normal brain, usually rendering them “elusive” to effective resection, irradiation, chemotherapy, or gene therapy. We demonstrate that neural stem cells (NSCs), when implanted into experimental intracranial gliomas in vivo in adult rodents, distribute themselves quickly and extensively throughout the tumor bed and migrate uniquely in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to stably express a foreign gene. The NSCs “surround” the invading tumor border while “chasing down” infiltrating tumor cells. When implanted intracranially at distant sites from the tumor (e.g., into normal tissue, into the contralateral hemisphere, or into the cerebral ventricles), the donor cells migrate through normal tissue targeting the tumor cells (including human glioblastomas). When implanted outside the CNS intravascularly, NSCs will target an intracranial tumor. NSCs can deliver a therapeutically relevant molecule—cytosine deaminase—such that quantifiable reduction in tumor burden results. These data suggest the adjunctive use of inherently migratory NSCs as a delivery vehicle for targeting therapeutic genes and vectors to refractory, migratory, invasive brain tumors. More broadly, they suggest that NSC migration can be extensive, even in the adult brain and along nonstereotypical routes, if pathology (as modeled here by tumor) is present. PMID:11070094

  9. Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals

    PubMed Central

    Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

    2014-01-01

    Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. PMID:24397462

  10. Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals.

    PubMed

    Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

    2014-04-01

    Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. PMID:24397462

  11. Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

    PubMed Central

    Gurney, J. G.; van Wijngaarden, E.

    1999-01-01

    Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (EMF) has now been conducted for over two decades. Cancer epidemiology studies in relation to EMF have focused primarily on brain cancer and leukemia, both from residential sources of exposure in children and adults and from occupational exposure in adult men. Because genotoxic effects of EMF have not been shown, most recent laboratory research has attempted to show biological effects that could be related to cancer promotion. In this report, we briefly review residential and occupational EMF studies on brain cancer. We also provide a general review of experimental studies as they relate both to the biological plausibility of an EMF-brain cancer relation and to the insufficiency of such research to help guide exposure assessment in epidemiologic studies. We conclude from our review that no recent research, either epidemiologic or experimental, has emerged to provide reasonable support for a causal role of EMF on brain cancer. PMID:11550314

  12. Arginine vasotocin neuronal development and its projection in the adult brain of the medaka.

    PubMed

    Kagawa, Nao; Honda, Akira; Zenno, Akiko; Omoto, Ryosuke; Imanaka, Saya; Takehana, Yusuke; Naruse, Kiyoshi

    2016-02-01

    The neurohypophysial peptide arginine vasotocin (AVT) and its mammalian ortholog arginine vasopressin function in a wide range of physiological and behavioral events. Here, we generated a new line of transgenic medaka (Oryzias latipes), which allowed us to monitor AVT neurons by enhanced green fluorescent protein (EGFP) and demonstrate AVT neuronal development in the embryo and the projection of AVT neurons in the adult brain of avt-egfp transgenic medaka. The onset of AVT expression manifested at 2 days postfertilization (dpf) as a pair of signals in the telencephalon of the brain. The telencephalic AVT neurons migrated and converged on the preoptic area (POA) by 4dpf. At the same stage, another onset of AVT expression manifested in the central optic tectum (OT), and they migrated to the ventral part of the hypothalamus (VH) by 6dpf. In the adult brain, the AVT somata with EGFP signals existed in the gigantocellular POA (gPOA), magnocellular POA (mPOA), and parvocellular POA (pPOA) and in the VH. Whereas the major projection of AVT fibers was found from the pPOA and VH to the posterior pituitary, it was also found that AVT neurons in the three POAs send their fibers into wide regions of the brain such as the telencephalon, mesencephalon and diencephalon. This study suggests that the avt-egfp transgenic medaka is a useful model to explore AVT neuronal development and function. PMID:26739197

  13. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    PubMed

    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype. PMID:27298360

  14. Brain white matter structure and COMT gene are linked to second-language learning in adults

    PubMed Central

    Mamiya, Ping C.; Richards, Todd L.; Coe, Bradley P.; Eichler, Evan E.; Kuhl, Patricia K.

    2016-01-01

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects’ grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype. PMID:27298360

  15. Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X

    PubMed Central

    Haesler, Sebastian; Rochefort, Christelle; Georgi, Benjamin; Licznerski, Pawel; Osten, Pavel; Scharff, Constance

    2007-01-01

    The gene encoding the forkhead box transcription factor, FOXP2, is essential for developing the full articulatory power of human language. Mutations of FOXP2 cause developmental verbal dyspraxia (DVD), a speech and language disorder that compromises the fluent production of words and the correct use and comprehension of grammar. FOXP2 patients have structural and functional abnormalities in the striatum of the basal ganglia, which also express high levels of FOXP2. Since human speech and learned vocalizations in songbirds bear behavioral and neural parallels, songbirds provide a genuine model for investigating the basic principles of speech and its pathologies. In zebra finch Area X, a basal ganglia structure necessary for song learning, FoxP2 expression increases during the time when song learning occurs. Here, we used lentivirus-mediated RNA interference (RNAi) to reduce FoxP2 levels in Area X during song development. Knockdown of FoxP2 resulted in an incomplete and inaccurate imitation of tutor song. Inaccurate vocal imitation was already evident early during song ontogeny and persisted into adulthood. The acoustic structure and the duration of adult song syllables were abnormally variable, similar to word production in children with DVD. Our findings provide the first example of a functional gene analysis in songbirds and suggest that normal auditory-guided vocal motor learning requires FoxP2. PMID:18052609

  16. Norepinephrine Modulates Coding of Complex Vocalizations in the Songbird Auditory Cortex Independent of Local Neuroestrogen Synthesis.

    PubMed

    Ikeda, Maaya Z; Jeon, Sung David; Cowell, Rosemary A; Remage-Healey, Luke

    2015-06-24

    The catecholamine norepinephrine plays a significant role in auditory processing. Most studies to date have examined the effects of norepinephrine on the neuronal response to relatively simple stimuli, such as tones and calls. It is less clear how norepinephrine shapes the detection of complex syntactical sounds, as well as the coding properties of sensory neurons. Songbirds provide an opportunity to understand how auditory neurons encode complex, learned vocalizations, and the potential role of norepinephrine in modulating the neuronal computations for acoustic communication. Here, we infused norepinephrine into the zebra finch auditory cortex and performed extracellular recordings to study the modulation of song representations in single neurons. Consistent with its proposed role in enhancing signal detection, norepinephrine decreased spontaneous activity and firing during stimuli, yet it significantly enhanced the auditory signal-to-noise ratio. These effects were all mimicked by clonidine, an α-2 receptor agonist. Moreover, a pattern classifier analysis indicated that norepinephrine enhanced the ability of single neurons to accurately encode complex auditory stimuli. Because neuroestrogens are also known to enhance auditory processing in the songbird brain, we tested the hypothesis that norepinephrine actions depend on local estrogen synthesis. Neither norepinephrine nor adrenergic receptor antagonist infusion into the auditory cortex had detectable effects on local estradiol levels. Moreover, pretreatment with fadrozole, a specific aromatase inhibitor, did not block norepinephrine's neuromodulatory effects. Together, these findings indicate that norepinephrine enhances signal detection and information encoding for complex auditory stimuli by suppressing spontaneous "noise" activity and that these actions are independent of local neuroestrogen synthesis. PMID:26109659

  17. Rhythmic Continuous-Time Coding in the Songbird Analog of Vocal Motor Cortex.

    PubMed

    Lynch, Galen F; Okubo, Tatsuo S; Hanuschkin, Alexander; Hahnloser, Richard H R; Fee, Michale S

    2016-05-18

    Songbirds learn and produce complex sequences of vocal gestures. Adult birdsong requires premotor nucleus HVC, in which projection neurons (PNs) burst sparsely at stereotyped times in the song. It has been hypothesized that PN bursts, as a population, form a continuous sequence, while a different model of HVC function proposes that both HVC PN and interneuron activity is tightly organized around motor gestures. Using a large dataset of PNs and interneurons recorded in singing birds, we test several predictions of these models. We find that PN bursts in adult birds are continuously and nearly uniformly distributed throughout song. However, we also find that PN and interneuron firing rates exhibit significant 10-Hz rhythmicity locked to song syllables, peaking prior to syllable onsets and suppressed prior to offsets-a pattern that predominates PN and interneuron activity in HVC during early stages of vocal learning. PMID:27196977

  18. In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan

    PubMed Central

    Betts, Matthew J.; Cardenas-Blanco, Arturo; Yang, Shan; Nestor, Peter J.

    2016-01-01

    Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)—a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N = 116 healthy adults (20–79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM–age associations were identified in several deep-brain nuclei—chiefly the striatum and midbrain—and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitable in vivo imaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions. SIGNIFICANCE STATEMENT This study used a whole-brain imaging approach known as quantitative susceptibility mapping (QSM) to provide a novel insight into iron accumulation in the brain across the adult lifespan. Validity of the method was demonstrated by showing concordance with ROI

  19. Pattern-Induced Covert Category Learning in Songbirds.

    PubMed

    Comins, Jordan A; Gentner, Timothy Q

    2015-07-20

    Language is uniquely human, but its acquisition may involve cognitive capacities shared with other species. During development, language experience alters speech sound (phoneme) categorization. Newborn infants distinguish the phonemes in all languages but by 10 months show adult-like greater sensitivity to native language phonemic contrasts than non-native contrasts. Distributional theories account for phonetic learning by positing that infants infer category boundaries from modal distributions of speech sounds along acoustic continua. For example, tokens of the sounds /b/ and /p/ cluster around different mean voice onset times. To disambiguate overlapping distributions, contextual theories propose that phonetic category learning is informed by higher-level patterns (e.g., words) in which phonemes normally occur. For example, the vowel sounds /Ι/ and /e/ can occupy similar perceptual spaces but can be distinguished in the context of "with" and "well." Both distributional and contextual cues appear to function in speech acquisition. Non-human species also benefit from distributional cues for category learning, but whether category learning benefits from contextual information in non-human animals is unknown. The use of higher-level patterns to guide lower-level category learning may reflect uniquely human capacities tied to language acquisition or more general learning abilities reflecting shared neurobiological mechanisms. Using songbirds, European starlings, we show that higher-level pattern learning covertly enhances categorization of the natural communication sounds. This observation mirrors the support for contextual theories of phonemic category learning in humans and demonstrates a general form of learning not unique to humans or language. PMID:26119748

  20. Female song is widespread and ancestral in songbirds.

    PubMed

    Odom, Karan J; Hall, Michelle L; Riebel, Katharina; Omland, Kevin E; Langmore, Naomi E

    2014-01-01

    Bird song has historically been considered an almost exclusively male trait, an observation fundamental to the formulation of Darwin's theory of sexual selection. Like other male ornaments, song is used by male songbirds to attract females and compete with rivals. Thus, bird song has become a textbook example of the power of sexual selection to lead to extreme neurological and behavioural sex differences. Here we present an extensive survey and ancestral state reconstruction of female song across songbirds showing that female song is present in 71% of surveyed species including 32 families, and that females sang in the common ancestor of modern songbirds. Our results reverse classical assumptions about the evolution of song and sex differences in birds. The challenge now is to identify whether sexual selection alone or broader processes, such as social or natural selection, best explain the evolution of elaborate traits in both sexes. PMID:24594930

  1. Human mutant huntingtin disrupts vocal learning in transgenic songbirds.

    PubMed

    Liu, Wan-Chun; Kohn, Jessica; Szwed, Sarah K; Pariser, Eben; Sepe, Sharon; Haripal, Bhagwattie; Oshimori, Naoki; Marsala, Martin; Miyanohara, Atsushi; Lee, Ramee

    2015-11-01

    Speech and vocal impairments characterize many neurological disorders. However, the neurogenetic mechanisms of these disorders are not well understood, and current animal models do not have the necessary circuitry to recapitulate vocal learning deficits. We developed germline transgenic songbirds, zebra finches (Taneiopygia guttata) expressing human mutant huntingtin (mHTT), a protein responsible for the progressive deterioration of motor and cognitive function in Huntington's disease (HD). Although generally healthy, the mutant songbirds had severe vocal disorders, including poor vocal imitation, stuttering, and progressive syntax and syllable degradation. Their song abnormalities were associated with HD-related neuropathology and dysfunction of the cortical-basal ganglia (CBG) song circuit. These transgenics are, to the best of our knowledge, the first experimentally created, functional mutant songbirds. Their progressive and quantifiable vocal disorder, combined with circuit dysfunction in the CBG song system, offers a model for genetic manipulation and the development of therapeutic strategies for CBG-related vocal and motor disorders. PMID:26436900

  2. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults.

    PubMed

    Chapman, Sandra B; Aslan, Sina; Spence, Jeffrey S; Keebler, Molly W; DeFina, Laura F; Didehbani, Nyaz; Perez, Alison M; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  3. Promoting brain health through exercise and diet in older adults: a physiological perspective.

    PubMed

    Jackson, Philippa A; Pialoux, Vincent; Corbett, Dale; Drogos, Lauren; Erickson, Kirk I; Eskes, Gail A; Poulin, Marc J

    2016-08-15

    The rise in incidence of age-related cognitive impairment is a global health concern. Ageing is associated with a number of changes in the brain that, collectively, contribute to the declines in cognitive function observed in older adults. Structurally, the ageing brain atrophies as white and grey matter volumes decrease. Oxidative stress and inflammation promote endothelial dysfunction thereby hampering cerebral perfusion and thus delivery of energy substrates and nutrients. Further, the development of amyloid plaques and neurofibrillary tangles contributes to neuronal loss. Of interest, there are substantial inter-individual differences in the degree to which these physical and functional changes impact upon cognitive function as we grow older. This review describes how engaging in physical activity and cognitive activities and adhering to a Mediterranean style diet promote 'brain health'. From a physiological perspective, we discuss the effects of these modifiable lifestyle behaviours on the brain, and how some recent human trials are beginning to show some promise as to the effectiveness of lifestyle behaviours in combating cognitive impairment. Moreover, we propose that these lifestyle behaviours, through numerous mechanisms, serve to increase brain, cerebrovascular and cognitive reserve, thereby preserving and enhancing cognitive function for longer. PMID:27524792

  4. The Whole-Brain N-Acetylaspartate Correlates with Education in Normal Adults

    PubMed Central

    Glodzik, Lidia; Wu, William E.; Babb, James S.; Achtnichts, Lutz; Amann, Michael; Sollberger, Marc; Monsch, Andreas U.; Gass, Achim; Gonen, Oded

    2012-01-01

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis 97 middle aged to elderly subjects (51–89 years old, 38% women) underwent brain MRI and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount with the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject’s educational attainment was the sum of their years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51–70 years old) participants. In this group education explained 21% variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristic predisposing to higher achievements later in life. We offer that late life WBNAA may be more affected by other like factors acting at midlife and later. PMID:23177924

  5. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults

    PubMed Central

    Chapman, Sandra B.; Aslan, Sina; Spence, Jeffrey S.; Keebler, Molly W.; DeFina, Laura F.; Didehbani, Nyaz; Perez, Alison M.; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56–75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  6. Clinical significance of brain white matter hyperintensities in young adults with psychiatric illness.

    PubMed

    Breeze, Janis L; Hesdorffer, Dale C; Hong, Xiaoni; Frazier, Jean A; Renshaw, Perry F

    2003-01-01

    Magnetic resonance imaging (MRI) provides detailed images of brain anatomy, with especially clear definition of gray and white matter structures. Several brain MRI studies have suggested that adults with bipolar disorder (BD) are more likely to have "white matter hyperintensities" (WMH) than adults without BD. The disproportionately greater frequency of these lesions in otherwise physically healthy patients suggests that the illness itself, or treatments used to control the illness, may be risk factors for the development of white matter changes. Similarly, WMH may be an etiological factor for some types of BD. In addition to reviewing the relevant literature, this research study attempted to determine whether lithium treatment is associated with an increased prevalence of WMH in young adults with psychiatric illness. To test this hypothesis, we evaluated over 600 brain MRI scans from inpatients at McLean Hospital, Belmont, Massachusetts. We controlled for possible confounding variables such as age, vascular disease, substance abuse, and markers of illness severity. We found that individuals with BD were no more likely to have WMH than other psychiatric patients. Lithium use was nonsignificantly associated with the presence of WMH. A multivariate regression model for the presence of WMH showed that heart disease, female gender, and multiple psychiatric admissions were significant predictors of WMH. This study does not support previous findings that BD, compared to other psychiatric illnesses, was associated with increased risk of WMH. Lithium use may be subtly associated with WMH. Our results are consistent with previous research that found an association between cardiovascular disease, advanced age, and the presence of WMH, though our analysis appears to be unique in its inclusion of cardiovascular disease as a risk factor in young adults with psychiatric illness. PMID:14555427

  7. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  8. Cyclophilin D-Sensitive Mitochondrial Permeability Transition in Adult Human Brain and Liver Mitochondria

    PubMed Central

    Morota, Saori; Chen, Li; Matsuyama, Nagahisa; Suzuki, Yoshiaki; Nakajima, Satoshi; Tanoue, Tadashi; Omi, Akibumi; Shibasaki, Futoshi; Shimazu, Motohide; Ikeda, Yukio; Uchino, Hiroyuki; Elmér, Eskil

    2011-01-01

    Abstract The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic target. The objective of this study was to validate the presence of a CypD-sensitive mPT in adult human brain and liver mitochondria. In order to perform functional characterization of human mitochondria, fresh tissue samples were obtained during hemorrhage or tumor surgery and mitochondria were rapidly isolated. Mitochondrial calcium retention capacity, a quantitative assay for mPT, was significantly increased by the CypD inhibitor cyclosporin A in both human brain and liver mitochondria, whereas thiol-reactive compounds and oxidants sensitized mitochondria to calcium-induced mPT. Brain mitochondria underwent swelling upon calcium overload, which was reversible upon calcium removal. To further explore mPT of human mitochondria, liver mitochondria were demonstrated to exhibit several classical features of the mPT phenomenon, such as calcium-induced loss of membrane potential and respiratory coupling, as well as release of the pro-apoptotic protein cytochrome c. We concluded that adult viable human brain and liver mitochondria possess an active CypD-sensitive mPT. Our findings support the rationale of CypD and mPT inhibition as pharmacological targets in acute and chronic neurodegeneration. PMID:21121808

  9. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

  10. Acquisition of Visual Perception in Blind Adults Using the BrainPort Artificial Vision Device

    PubMed Central

    Pintar, Christine; Arnoldussen, Aimee; Fisher, Christopher

    2015-01-01

    OBJECTIVE. We sought to determine whether intensive low vision rehabilitation would confer any functional improvement in a sample of blind adults using the BrainPort artificial vision device. METHOD. Eighteen adults ages 28–69 yr (n = 10 men and n = 8 women) who had light perception only or worse vision bilaterally spent up to 6 hr per day for 1 wk undergoing structured rehabilitation interventions. The functional outcomes of object identification and word recognition were tested at baseline and after rehabilitation training. RESULTS. At baseline, participants were unable to complete the two functional assessments. After participation in the 1-wk training protocol, participants were able to use the BrainPort device to complete the two tasks with moderate success. CONCLUSION. Without training, participants were not able to perform above chance level using the BrainPort device. As artificial vision technologies become available, occupational therapy practitioners can play a key role in clients’ success or failure in using these devices. PMID:25553750

  11. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  12. Differential, regional, and cellular expression of the stathmin family transcripts in the adult rat brain.

    PubMed

    Ozon, S; El Mestikawy, S; Sobel, A

    1999-06-01

    Stathmin is a ubiquitous cytosolic phosphoprotein, preferentially expressed in the nervous system, and previously described as a relay integrating diverse intracellular signaling pathways. Stathmin is the generic element of a mammalian protein family including SCG10, SCLIP, and RB3 with its splice variants RB3' and RB3". In contrast with stathmin, SCG10, SCLIP, and RB3/RB3'/RB3" are exclusively expressed in the nervous system, stathmin and SCG10 being mostly expressed during cell proliferation and differentiation, and SCLIP and RB3 rather in mature neural cells. To further understand their specific roles in the CNS, we compared the localization of the stathmin, SCG10, SCLIP, and RB3 transcripts in adult rat brain. Northern blot analysis as well as in situ hybridization experiments showed that all stathmin-related mRNAs are expressed in a wide range of adult rat brain areas. At a regional level, SCG10 and SCLIP appear generally distributed similarly except in a few areas. The pattern of expression of the RB3 transcript is very different from that of the three other members of the stathmin family. Furthermore, unlike SCG10 and SCLIP, which were detected only in neurons, but like stathmin, RB3 was detected in neurons and also in glial cells of the white matter. Altogether, our results suggest distinct roles for each member of the stathmin-related phosphoprotein family, in regard to their specific regional and cellular localization in the rat brain. PMID:10369222

  13. In vivo quantification of brain injury in adult Niemann-Pick Disease Type C.

    PubMed

    Zaaraoui, Wafaa; Crespy, Lydie; Rico, Audrey; Faivre, Anthony; Soulier, Elisabeth; Confort-Gouny, Sylviane; Cozzone, Patrick J; Pelletier, Jean; Ranjeva, Jean-Philippe; Kaphan, Elsa; Audoin, Bertrand

    2011-06-01

    Development of surrogate markers is necessary to assess the potential efficacy of new therapeutics in Niemann-Pick Disease Type C (NP-C). In the present study, magnetization transfer ratio (MTR) imaging, a quantitative MRI imaging technique sensitive to subtle brain microstructural changes, was applied in two patients suffering from adult NP-C. Statistical mapping analysis was performed to compare each patient's MTR maps with those of a group of 34 healthy controls to quantify and localize the extent of brain injury of each patient. Using this method, pathological changes were evidenced in the cerebellum, the thalami and the lenticular nuclei in both patients and also in the fronto-temporal cortices in the patient with the worse functional deficit. In addition, white matter changes were located in the midbrain, the cerebellum and the fronto-temporal lobes in the patient with the higher level of disability and in only one limited periventricular white matter region in the other patient. A 6-month follow-up was performed in the patient with the lower functional deficit and evidenced significant extension of grey matter (GM) and white matter (WM) injuries during the following period (14% of increased injury for GM and 53% for WM). This study demonstrates that significant brain injury related to clinical deficit can be assessed in vivo in adult NP-C using MTR imaging. Although preliminary, these findings suggest that MTR imaging may be a relevant candidate for the development of biomarker in NP-C. PMID:21397539

  14. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    PubMed

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. PMID:24931850

  15. An ultrastructural study of the phagocytic activity of astrocytes in adult rat brain.

    PubMed Central

    al-Ali, S Y; al-Hussain, S M

    1996-01-01

    The role of adult astrocytes in the removal of cell debris and foreign particles following injury to the brain is controversial. This study was undertaken to elucidate the response of adult astrocytes to needle injury of the rat cerebral cortex, using a suspension of colloidal carbon as a marker for phagocytosis. Either a single or 2 successive injections of colloidal carbon suspension were made into the cerebral cortex. The animals were allowed to survive for periods of from 1 to 30 d. Unequivocal involvement of astrocytes in the removal of carbon particles was evident only in those brains which had been subjected to 2 successive injections of carbon. The particles were located in membrane-bound vacuoles and were subsequently sequestered in lysosomes. Carbon-containing astrocytes were observed in the immediate vicinity of the lesion, in the adjacent parenchyma, around blood vessels and abutting carbon-containing macrophages. This study demonstrates that adult astrocytes are involved in phagocytosis, but only as a second line of defence. The possible significance of carbon-laden astrocytes further away from the site of the lesion is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8621323

  16. Traumatic Brain Injury Causes Aberrant Migration of Adult-Born Neurons in the Hippocampus

    PubMed Central

    Ibrahim, Sara; Hu, Weipeng; Wang, Xiaoting; Gao, Xiang; He, Chunyan; Chen, Jinhui

    2016-01-01

    Traumatic brain injury (TBI) promotes neural stem/progenitor cell (NSC) proliferation in an attempt to initiate innate repair mechanisms. However, all immature neurons in the CNS are required to migrate from their birthplace to their final destination to develop into functional neurons. Here we assessed the destination of adult-born neurons following TBI. We found that a large percentage of immature neurons migrated past their normal stopping site at the inner granular cell layer (GCL), and became misplaced in the outer GCL of the hippocampal dentate gyrus. The aberrant migration of adult-born neurons in the hippocampus occurred 48 hours after TBI, and lasted for 8 weeks, resulting in a great number of newly generated neurons misplaced in the outer GCL in the hippocampus. Those misplaced neurons were able to become mature and differentiate into granular neurons, but located ectopically in the outer GCL with reduced dendritic complexity after TBI. The adult-born neurons at the misplaced position may make wrong connections with inappropriate nearby targets in the pre-existing neural network. These results suggest that although stimulation of endogenous NSCs following TBI might offer new avenues for cell-based therapy, additional intervention is required to further enhance successful neurogenesis for repairing the damaged brain. PMID:26898165

  17. Acute effect of a high nitrate diet on brain perfusion in older adults

    PubMed Central

    Presley, Tennille D.; Morgan, Ashley R.; Bechtold, Erika; Clodfelter, William; Dove, Robin W.; Jennings, Janine M.; Kraft, Robert A.; King, S. Bruce; Laurienti, Paul J.; Rejeski, W. Jack; Burdette, Jonathan H.; Kim-Shapiro, Daniel B.; Miller, Gary D.

    2010-01-01

    Aims Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and Results In this investigation we administered a high vs. low nitrate diet to older adults (74.7 ± 6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. Conclusion These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning. PMID:20951824

  18. Traumatic Brain Injury among Older Adults at Level I and II Trauma Centers

    PubMed Central

    Cuthbert, Jeffrey P.; Whyte, John; Corrigan, John D.; Faul, Mark; Harrison-Felix, Cynthia

    2013-01-01

    Abstract Individuals 65 years of age and over have the highest rates of traumatic brain injury (TBI)-related hospitalizations and deaths, and older adults (defined variably across studies) have particularly poor outcomes after TBI. The factors predicting these outcomes remain poorly understood, and age-specific care guidelines for TBI do not exist. This study provides an overview of TBI in older adults using data from the National Trauma Data Bank (NTDB) gathered between 2007 and 2010, evaluates age group-specific trends in rates of TBI over time using U.S. Census data, and examines whether routinely collected information is able to predict hospital discharge status among older adults with TBI in the NTDB. Results showed a 20–25% increase in trauma center admissions for TBI among the oldest age groups (those >=75 years), relative to the general population, between 2007 and 2010. Older adults (>=65 years) with TBI tended to be white females who have incurred an injury from a fall resulting in a “severe” Abbreviated Injury Scale (AIS) score of the head. Older adults had more in-hospital procedures, such as neuroimaging and neurosurgery, tended to experience longer hospital stays, and were more likely to require continued medical care than younger adults. Older age, injury severity, and hypotension increased the odds of in-hospital death. The public health burden of TBI among older adults will likely increase as the Baby Boom generation ages. Improved primary and secondary prevention of TBI in this cohort is needed. PMID:23962046

  19. Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

    PubMed Central

    Fried, Nathan T.; Moffat, Cynthia; Seifert, Erin L.

    2014-01-01

    Mitochondrial dysfunction has been implicated in many neurological disorders that only develop or are much more severe in adults, yet no methodology exists that allows for medium-throughput functional mitochondrial analysis of brain sections from adult animals. We developed a technique for quantifying mitochondrial respiration in acutely isolated adult rat brain sections with the Seahorse XF Analyzer. Evaluating a range of conditions made quantifying mitochondrial function from acutely derived adult brain sections from the cortex, cerebellum, and trigeminal nucleus caudalis possible. Optimization of this technique demonstrated that the ideal section size was 1 mm wide. We found that sectioning brains at physiological temperatures was necessary for consistent metabolic analysis of trigeminal nucleus caudalis sections. Oxygen consumption in these sections was highly coupled to ATP synthesis, had robust spare respiratory capacities, and had limited nonmitochondrial respiration, all indicative of healthy tissue. We demonstrate the effectiveness of this technique by identifying a decreased spare respiratory capacity in the trigeminal nucleus caudalis of a rat model of chronic migraine, a neurological disorder that has been associated with mitochondrial dysfunction. This technique allows for 24 acutely isolated sections from multiple brain regions of a single adult rat to be analyzed simultaneously with four sequential drug treatments, greatly advancing the ability to study mitochondrial physiology in adult neurological disorders. PMID:25252946

  20. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo

    PubMed Central

    Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain. PMID:26466323

  1. Negotiation of territorial boundaries in a songbird.

    PubMed

    Vehrencamp, Sandra L; Ellis, Jesse M; Cropp, Brett F; Koltz, John M

    2014-11-01

    How do territorial neighbors resolve the location of their boundaries? We addressed this question by testing the predictions of 2 nonexclusive game theoretical models for competitive signaling: the sequential assessment game and the territorial bargaining game. Our study species, the banded wren, is a neotropical nonmigratory songbird living in densely packed territorial neighborhoods. The males possess repertoires of approximately 25 song types that are largely shared between neighbors and sequentially delivered with variable switching rates. Over 3 days, boundary disputes among pairs of neighboring males were synchronously recorded, their perch positions were marked, and their behavioral interactions were noted. For each countersinging interaction between 2 focal males, we quantified approach and retreat order, a variety of song and call patterns, closest approach distance, distance from the territorial center, and female presence. Aggressors produced more rattle-buzz songs during the approaching phase of interactions, whereas defenders overlapped their opponent's songs. During the close phase of the interaction, both males matched frequently, but the key determinant of which one retreated first was song-type diversity-first retreaters sang with a higher diversity. Retreaters also produced more unshared song types during the interaction, and in the retreating phase of the interaction, they overlapped more. A negative correlation between song-type diversity asymmetry and contest duration suggested sequential assessment of motivational asymmetry. The use of this graded signal, which varied with distance from the center and indicated a male's motivation to defend a particular position, supported the bargaining model. The bargaining game could be viewed as a series of sequential assessment contests. PMID:25419086

  2. Negotiation of territorial boundaries in a songbird

    PubMed Central

    Ellis, Jesse M.; Cropp, Brett F.; Koltz, John M.

    2014-01-01

    How do territorial neighbors resolve the location of their boundaries? We addressed this question by testing the predictions of 2 nonexclusive game theoretical models for competitive signaling: the sequential assessment game and the territorial bargaining game. Our study species, the banded wren, is a neotropical nonmigratory songbird living in densely packed territorial neighborhoods. The males possess repertoires of approximately 25 song types that are largely shared between neighbors and sequentially delivered with variable switching rates. Over 3 days, boundary disputes among pairs of neighboring males were synchronously recorded, their perch positions were marked, and their behavioral interactions were noted. For each countersinging interaction between 2 focal males, we quantified approach and retreat order, a variety of song and call patterns, closest approach distance, distance from the territorial center, and female presence. Aggressors produced more rattle-buzz songs during the approaching phase of interactions, whereas defenders overlapped their opponent’s songs. During the close phase of the interaction, both males matched frequently, but the key determinant of which one retreated first was song-type diversity—first retreaters sang with a higher diversity. Retreaters also produced more unshared song types during the interaction, and in the retreating phase of the interaction, they overlapped more. A negative correlation between song-type diversity asymmetry and contest duration suggested sequential assessment of motivational asymmetry. The use of this graded signal, which varied with distance from the center and indicated a male’s motivation to defend a particular position, supported the bargaining model. The bargaining game could be viewed as a series of sequential assessment contests. PMID:25419086

  3. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    PubMed

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. PMID:26315689

  4. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides

    PubMed Central

    Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two– polyR and Trans – that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael’s addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues. PMID:25894337

  5. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects. PMID:20395146

  6. Adult axolotls can regenerate original neuronal diversity in response to brain injury.

    PubMed

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. PMID:27156560

  7. Beyond utterances: distributed cognition as a framework for studying discourse in adults with acquired brain injury.

    PubMed

    Duff, Melissa C; Mutlu, Bilge; Byom, Lindsey; Turkstra, Lyn S

    2012-02-01

    Considerable effort has been directed at understanding the nature of the communicative deficits observed in individuals with acquired brain injuries. Yet several theoretical, methodological, and clinical challenges remain. In this article, we examine distributed cognition as a framework for understanding interaction among communication partners, interaction of communication and cognition, and interaction with the environments and contexts of everyday language use. We review the basic principles of distributed cognition and the implications for applying this approach to the study of discourse in individuals with cognitive-communication disorders. We also review a range of protocols and findings from our research that highlight how the distributed cognition approach might offer a deeper understanding of communicative mechanisms and deficits in individuals with cognitive communication impairments. The advantages and implications of distributed cognition as a framework for studying discourse in adults with acquired brain injury are discussed. PMID:22362323

  8. Brain activation deficit in increased-load working memory tasks among adults with ADHD using fMRI.

    PubMed

    Ko, Chih-Hung; Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Lin, Wei-Chen; Wang, Peng-Wei; Liu, Gin-Chung

    2013-10-01

    Working memory (WM) is impaired among adults with attention-deficit hyperactivity disorder (ADHD). This study aimed to investigate the brain activation deficit for low-level or increased-load WM among adults with ADHD. A total of 20 adults with ADHD and controls were recruited according to diagnostic interviewing by a psychiatrist. Phonological and visual-spatial 2-back and 3-back tasks were performed under functional magnetic resonance scanning. The results demonstrated that both the adults with ADHD and the controls exhibited activation of the fronto-parietal network for WM, and the intensity was greater in the adult ADHD group. The ADHD group had higher brain activation over the bilateral anterior cingulate, left inferior frontal lobe, hippocampus, and supplementary motor area (SMA) for phonological WM than the control group. When the task loading increased from 2-back to 3-back tasks, the adults with ADHD perceived greater difficulty. The control group exhibited increased brain activation over the frontal-parietal network in response to increased phonological WM load. However, the ADHD group showed decreased brain activation over the left precuneus, insula, and SMA. Further analysis demonstrated that the ADHD group exhibited a greater decrease in brain activation over the left fronto-parietal network, including the precuneus, SMA, insula/inferior frontal lobe, and dorsolateral prefrontal cortex, than the control group. These results suggest that adults with ADHD pay more effort to low demanding phonological WM. On the other hand, brain activation of the left fronto-parietal network is impaired when the demands of WM exceed the capacity of adults with ADHD. PMID:23645101

  9. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    PubMed Central

    Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression.Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells. PMID:22952666

  10. Netrin-5 is highly expressed in neurogenic regions of the adult brain

    PubMed Central

    Yamagishi, Satoru; Yamada, Kohei; Sawada, Masato; Nakano, Suguru; Mori, Norio; Sawamoto, Kazunobu; Sato, Kohji

    2015-01-01

    Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain. PMID:25941474

  11. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  12. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain.

    PubMed

    Resnick, Susan M; Pham, Dzung L; Kraut, Michael A; Zonderman, Alan B; Davatzikos, Christos

    2003-04-15

    Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 nondemented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults. Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p < 0.001) and white (p < 0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 +/- 0.3, 2.4 +/- 0.4, and 3.1 +/- 0.4 cm3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 +/- 0.1 cm3 per year (3.7, 1.3, 2.4, and 1.2 cm3, respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline. Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults. These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy. PMID:12716936

  13. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring

    PubMed Central

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-01-01

    Introduction The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. Methods To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. Results The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. Conclusions These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood. PMID:25642385

  14. APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults: A STROBE Article.

    PubMed

    Su, Yun Yan; Liang, Xue; Schoepf, U Joseph; Varga-Szemes, Akos; West, Henry C; Qi, Rongfeng; Kong, Xiang; Chen, Hui Juan; Lu, Guang Ming; Zhang, Long Jiang

    2015-12-01

    To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging.Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests.There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05).APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect. PMID:26717353

  15. Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA.

    PubMed Central

    Iñiguez, M A; Rodriguez-Peña, A; Ibarrola, N; Morreale de Escobar, G; Bernal, J

    1992-01-01

    The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods" of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Muñoz, A., A. Rodriguez-Peña, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a decreased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in either experimental situation. RC3 mRNA levels were not affected by food restriction demonstrating that the effect of hypothyroidism was not related to the lack of weight gain. The control of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations induced by hypothyroidism in the adult brain. Images PMID:1379612

  16. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    PubMed

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary. PMID:23022824

  17. Lesions targeted to the anterior forebrain disrupt vocal variability associated with testosterone-induced sensorimotor song development in adult female canaries, Serinus canaria.

    PubMed

    Rouse, Melvin L; Ball, Gregory F

    2016-01-01

    Learned communication was a trait observed in a limited number of vertebrates such as humans but also songbirds (i.e., species in the suborder passeri sometimes called oscines). Robust male-biased sex-differences in song development and production have been observed in several songbird species. However, in some of these species treating adult females with testosterone (T) induced neuro-behavioral changes such that females become more male-like in brain and behavior. T-treatment in these adult females seemed to stimulate sensorimotor song development to facilitate song masculinization. In male songbirds it was known that the lateral magnocellular nucleus of the anterior nidopallium (LMAN) played a modulatory role during song development. LMAN was androgen sensitive and may be a key target of a T-induced recapitulation of a developmental process in adult females. This hypothesis was tested. Adult female canaries were given either a chemical lesion of LMAN or a control sham-surgery. Prior to surgery birds were individually housed for 2-weeks in sound-attenuated chambers to record baseline vocal behavior. Post-surgery birds were given 1-week to recover before subcutaneous implantation with silastic capsules filled with crystalline-T. Birds remained on treatment for 3-weeks (behavioral recordings continued throughout). Birds with a lesion to LMAN had less variability in their song compared with controls. The diversity of syllable and phrase type(s) was greater in sham controls as compared with birds with LMAN lesions. Birds did not differ in song rate. These data suggested that the sustention and conclusion of T-induced sensorimotor song development in adult female canaries required an intact LMAN. PMID:25864444

  18. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. PMID:22484141

  19. Leptin replacement alters brain response to food cues in genetically leptin-deficient adults

    PubMed Central

    Baicy, Kate; London, Edythe D.; Monterosso, John; Wong, Ma-Li; Delibasi, Tuncay; Sharma, Anil; Licinio, Julio

    2007-01-01

    A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity. PMID:17986612

  20. Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

    PubMed Central

    Tajuddin, Nuzhath; Moon, Kwan-Hoon; Marshall, S. Alex; Nixon, Kimberly; Neafsey, Edward J.; Kim, Hee-Yong; Collins, Michael A.

    2014-01-01

    Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼9 g/kg/d, achieving blood ethanol levels ∼375 mg/dl; “Majchrowicz” model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA (p-cPLA2), secretory PLA2 GIIA (sPLA2) and PARP-1 in regions incurring extensive neurodegeneration in this model—hippocampus, entorhinal cortex, and olfactory bulb—but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2) levels and increased brain “oxidative stress footprints” (4-hydroxynonenal-adducted proteins). For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼60 d) were ethanol-binged (100 mM or ∼450 mg/dl) for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013). Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3), known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins). Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models

  1. Neurons diversify astrocytes in the adult brain through sonic hedgehog signaling.

    PubMed

    Farmer, W Todd; Abrahamsson, Therése; Chierzi, Sabrina; Lui, Christopher; Zaelzer, Cristian; Jones, Emma V; Bally, Blandine Ponroy; Chen, Gary G; Théroux, Jean-Francois; Peng, Jimmy; Bourque, Charles W; Charron, Frédéric; Ernst, Carl; Sjöström, P Jesper; Murai, Keith K

    2016-02-19

    Astrocytes are specialized and heterogeneous cells that contribute to central nervous system function and homeostasis. However, the mechanisms that create and maintain differences among astrocytes and allow them to fulfill particular physiological roles remain poorly defined. We reveal that neurons actively determine the features of astrocytes in the healthy adult brain and define a role for neuron-derived sonic hedgehog (Shh) in regulating the molecular and functional profile of astrocytes. Thus, the molecular and physiological program of astrocytes is not hardwired during development but, rather, depends on cues from neurons that drive and sustain their specialized properties. PMID:26912893

  2. Regrowth of Serotonin Axons in the Adult Mouse Brain Following Injury.

    PubMed

    Jin, Yunju; Dougherty, Sarah E; Wood, Kevin; Sun, Landy; Cudmore, Robert H; Abdalla, Aya; Kannan, Geetha; Pletnikov, Mikhail; Hashemi, Parastoo; Linden, David J

    2016-08-17

    It is widely believed that damaged axons in the adult mammalian brain have little capacity to regrow, thereby impeding functional recovery after injury. Studies using fixed tissue have suggested that serotonin neurons might be a notable exception, but remain inconclusive. We have employed in vivo two-photon microscopy to produce time-lapse images of serotonin axons in the neocortex of the adult mouse. Serotonin axons undergo massive retrograde degeneration following amphetamine treatment and subsequent slow recovery of axonal density, which is dominated by new growth with little contribution from local sprouting. A stab injury that transects serotonin axons running in the neocortex is followed by local regression of cut serotonin axons and followed by regrowth from cut ends into and across the stab rift zone. Regrowing serotonin axons do not follow the pathways left by degenerated axons. The regrown axons release serotonin and their regrowth is correlated with recovery in behavioral tests. PMID:27499084

  3. Effects of alcohol consumption on cognition and regional brain volumes among older adults.

    PubMed

    Downer, Brian; Jiang, Yang; Zanjani, Faika; Fardo, David

    2015-06-01

    This study utilized data from the Framingham Heart Study Offspring Cohort to examine the relationship between midlife and late-life alcohol consumption, cognitive functioning, and regional brain volumes among older adults without dementia or a history of abusing alcohol. The results from multiple linear regression models indicate that late life, but not midlife, alcohol consumption status is associated with episodic memory and hippocampal volume. Compared to late life abstainers, moderate consumers had larger hippocampal volume, and light consumers had higher episodic memory. The differences in episodic memory according to late life alcohol consumption status were no longer significant when hippocampal volume was included in the regression model. The findings from this study provide new evidence that hippocampal volume may contribute to the observed differences in episodic memory among older adults and late life alcohol consumption status. PMID:25202027

  4. Effects of Alcohol Consumption on Cognition and Regional Brain Volumes Among Older Adults

    PubMed Central

    Downer, Brian; Jiang, Yang; Zanjani, Faika; Fardo, David

    2015-01-01

    This study utilized data from the Framingham Heart Study Offspring Cohort to examine the relationship between midlife and late-life alcohol consumption, cognitive functioning, and regional brain volumes among older adults without dementia or a history of abusing alcohol. The results from multiple linear regression models indicate that late life, but not midlife, alcohol consumption status is associated with episodic memory and hippocampal volume. Compared to late life abstainers, moderate consumers had larger hippocampal volume, and light consumers had higher episodic memory. The differences in episodic memory according to late life alcohol consumption status were no longer significant when hippocampal volume was included in the regression model. The findings from this study provide new evidence that hippocampal volume may contribute to the observed differences in episodic memory among older adults and late life alcohol consumption status. PMID:25202027

  5. Language-related Cntnap2 gene is differentially expressed in sexually dimorphic song nuclei essential for vocal learning in songbirds

    PubMed Central

    Panaitof, S. Carmen; Abrahams, Brett S.; Dong, Hongmei; Geschwind, Daniel H.; White, Stephanie A.

    2010-01-01

    Multiple studies, involving distinct clinical populations, implicate contactin associated protein-like 2 (CNTNAP2) in aspects of language development and performance. While CNTNAP2 is broadly distributed in developing rodent brain, it shows a striking gradient of frontal cortical enrichment in developing human brain, consistent with a role in patterning circuits that subserve higher cognition and language. To test the hypothesis that CNTNAP2 may be important for learned vocal communication in additional species, we employed in situ hybridization to characterize transcript distribution in the zebra finch, an experimentally tractable songbird for which the neural substrate of this behavior is well-established. Consistent with an important role in learned vocalization, Cntnap2 was enriched or diminished in key song control nuclei relative to adjacent brain tissue. Importantly, this punctuated expression was observed in males, but not females, in accord with the sexual dimorphism of neural circuitry and vocal learning in this species. Ongoing functional work will provide important insights into the relationship between Cntnap2 and vocal communication in songbirds and thereby clarify mechanisms at play in disorders of human cognition and language. PMID:20394055

  6. Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain.

    PubMed Central

    Goldman, S A; Nottebohm, F

    1983-01-01

    The vocal control nucleus designated HVc (hyperstriatum ventrale, pars caudalis) of adult female canaries expands in response to systemic testosterone administration, which also induces the females to sing in a male-like manner. We became interested in the possibility of neurogenesis as a potential basis for this phenomenon. Intact adult female canaries were injected with [3H]thymidine over a 2-day period. Some birds were given testosterone implants at various times before thymidine. The birds were sacrificed 5 wk after hormone implantation, and their brains were processed for autoradiography. In parallel control experiments, some birds were given implants of cholesterol instead of testosterone. All birds showed considerable numbers of labeled neurons, glia, endothelia, and ventricular zone cells in and around HVc. Ultrastructural analysis confirmed the identity of these labeled neurons. Cholesterol- and testosterone-treated birds had similar neuronal labeling indices, which ranged from 1.8% to 4.0% in HVc. Thus, neurogenesis occurred in these adults independently of exogenous hormone treatment. Conversely, both glial and endothelial proliferation rates were markedly stimulated by exogenous testosterone treatment. We determined the origin of the thymidine-incorporating neurons by sacrificing two thymidine-treated females soon after their thymidine injections, precluding any significant migration of newly labeled cells. Analysis of these brains revealed no cells of neuronal morphology present in HVc but a very heavily labeled ventricular zone overlying HVc. We conclude that neuronal precursors exist in the HVc ventricular zone that incorporate tritiated thymidine during the S phase preceding their mitosis; after division these cells migrate into, and to some extent beyond, HVc. This ventricular zone neurogenesis seems to be a normally occurring phenomenon in intact adult female canaries. Images PMID:6572982

  7. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    SciTech Connect

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  8. Psychotherapy Interventions for Managing Anxiety and Depressive Symptoms in Adult Brain Tumor Patients: A Scoping Review

    PubMed Central

    Kangas, Maria

    2015-01-01

    Background Adult brain tumor (BT) patients and longer-term survivors are susceptible to experiencing emotional problems, including anxiety and/or depression disorders, which may further compromise their quality-of-life (QOL) and general well-being. The objective of this paper is to review psychological approaches for managing anxiety and depressive symptoms in adult BT patients. A review of psychological interventions comprising mixed samples of oncology patients, and which included BT patients is also evaluated. The review concludes with an overview of a recently developed transdiagnostic psychotherapy program, which was specifically designed to treat anxiety and/or depressive symptoms in adult BT patients. Methods Electronic databases (PsycINFO, Medline, Embase, and Cochrane) were searched to identify published studies investigating psychological interventions for managing anxiety and depressive symptoms in adult BT patients. Only four randomized controlled trials (RCTs) were identified. Results Only one of the RCTs tested a psychosocial intervention, which was specifically developed for primary BT patients, and which was found to improve QOL including existential well-being as well as reducing depressive symptoms. A second study tested a combined cognitive rehabilitation and problem-solving intervention, although was not found to significantly improve mood or QOL. The remaining two studies tested multidisciplinary psychosocial interventions in heterogeneous samples of cancer patients (included BT patients) with advanced stage disease. Maintenance of QOL was found in both studies, although no secondary gains were found for improvements in mood. Conclusion There is a notable paucity of psychological interventions for adult BT patients across the illness trajectory. Further research is required to strengthen the evidence base for psychological interventions in managing anxiety and depressive symptoms, and enhancing the QOL of distressed adults diagnosed with a BT

  9. Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.

    PubMed

    Nokia, Miriam S; Anderson, Megan L; Shors, Tracey J

    2012-12-01

    Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3-12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague-Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'. PMID:23039863

  10. On the relationship between cellular and hemodynamic properties of the human brain cortex throughout adult lifespan.

    PubMed

    Zhao, Yue; Wen, Jie; Cross, Anne H; Yablonskiy, Dmitriy A

    2016-06-01

    Establishing baseline MRI biomarkers for normal brain aging is significant and valuable for separating normal changes in the brain structure and function from different neurological diseases. In this paper for the first time we have simultaneously measured a variety of tissue specific contributions defining R2* relaxation of the gradient recalled echo (GRE) MRI signal in human brains of healthy adults (ages 22 to 74years) and related these measurements to tissue structural and functional properties. This was accomplished by separating tissue (R2t(⁎)) and extravascular BOLD contributions to the total tissue specific GRE MRI signal decay (R2(⁎)) using an advanced version of previously developed Gradient Echo Plural Contrast Imaging (GEPCI) approach and the acquisition and post-processing methods that allowed the minimization of artifacts related to macroscopic magnetic field inhomogeneities, and physiological fluctuations. Our data (20 healthy subjects) show that in most cortical regions R2t(⁎) increases with age while tissue hemodynamic parameters, i.e. relative oxygen extraction fraction (OEFrel), deoxygenated cerebral blood volume (dCBV) and tissue concentration of deoxyhemoglobin (Cdeoxy) remain practically constant. We also found the important correlations characterizing the relationships between brain structural and hemodynamic properties in different brain regions. Specifically, thicker cortical regions have lower R2t(⁎) and these regions have lower OEF. The comparison between GEPCI-derived tissue specific structural and functional metrics and literature information suggests that (a) regions in a brain characterized by higher R2t(⁎) contain higher concentration of neurons with less developed cellular processes (dendrites, spines, etc.), (b) regions in a brain characterized by lower R2t(⁎) represent regions with lower concentration of neurons but more developed cellular processes, and (c) the age-related increases in the cortical R2t(⁎) mostly

  11. Brain Volumetrics, Regional Cortical Thickness and Radiographic Findings in Adults with Cyanotic Congenital Heart Disease☆

    PubMed Central

    Cordina, Rachael; Grieve, Stuart; Barnett, Michael; Lagopoulos, Jim; Malitz, Nathan; Celermajer, David S.

    2014-01-01

    Background Chronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized. Hypothesis We hypothesized that adults with cyanotic CHD would have widespread changes including abnormal brain volumetric measures, decreased cortical thickness and an increased burden of small and large vessel ischemic changes. Methods Ten adults with chronic cyanosis from CHD (40 ± 4 years) and mean oxygen saturations of 82 ± 2% were investigated using quantitative MRI. Hematological and biochemical parameters were also assessed. All subjects were free from major physical or intellectual impairment. Brain volumetric results were compared with randomly selected age- and sex-matched controls from our database of normal subjects. Results Five of 10 cyanotic subjects had cortical lacunar infarcts. The white matter (WM) hyperintensity burden was also abnormally high (Scheltens Scale was 8 ± 2). Quantitative MRI revealed evidence of extensive generalized WM and gray matter (GM) volumetric loss; global GM volume was reduced in cyanosed subjects (630 ± 16 vs. 696 ± 14 mL in controls, p = 0.01) as was global WM volume (471 ± 10 vs. 564 ± 18 mL, p = 0.003). Ventricular cerebrospinal fluid volume was increased (35 ± 10 vs. 26 ± 5 mL, p = 0.002). There were widespread regions of local cortical thickness reduction observed across the brain. These changes included bilateral thickness reductions in the frontal lobe including the dorsolateral prefrontal cortex and precentral gyrus, the posterior parietal lobe and the middle temporal gyrus. Sub-cortical volume changes were observed in the caudate, putamen and in the thalamus (p ≤ 0.005 for all regions). Cortical GM volume negatively correlated with brain natriuretic peptide (R = − 0.89, p = 0.009), high sensitivity C-reactive protein (R = − 0

  12. Using bioacoustics to examine shifts in songbird phenology.

    PubMed

    Buxton, Rachel T; Brown, Emma; Sharman, Lewis; Gabriele, Christine M; McKenna, Megan F

    2016-07-01

    Monitoring patterns in biodiversity and phenology have become increasingly important given accelerating levels of anthropogenic change. Long-term monitoring programs have reported earlier occurrence of spring activity, reflecting species response to climate change. Although tracking shifts in spring migration represents a valuable approach to monitoring community-level consequences of climate change, robust long-term observations are challenging and costly. Audio recordings and metrics of bioacoustic activity could provide an effective method for monitoring changes in songbird activity and broader biotic interactions. We used 3 years of spring and fall recordings at six sites in Glacier Bay National Park, Alaska, an area experiencing rapid warming and glacial retreat, to examine the utility of bioacoustics to detect changes in songbird phenology. We calculated the Acoustic Complexity Index (ACI), an algorithm representing an index of bird community complexity. Abrupt changes in ACI values from winter to spring corresponded to spring transition, suggesting that ACI may be an effective, albeit coarse metric to detect the arrival of migrating songbirds. The first peak in ACI shifted from April 16 to April 11 from 2012 to 2014. Changes in ACI were less abrupt in the fall due to weather events, suggesting spring recordings are better suited to indicate phenology. To ensure changes in ACI values were detecting real changes in songbird activity, we explored the relationship between ACI and song of three species: varied thrush (Ixoreus naevius), Pacific wren (Troglodytes pacificus), and ruby-crowned kinglet (Regulus calendula). ACI was positively related to counts of all species, but most markedly with song of the varied thrush, the most common species in our recordings and a known indicator of forest ecosystem health. We conclude that acoustic recordings paired with bioacoustic indices may be a useful method of monitoring shifts in songbird communities due to climate

  13. A detailed viscoelastic characterization of the P17 and adult rat brain.

    PubMed

    Elkin, Benjamin S; Ilankovan, Ashok I; Morrison, Barclay

    2011-11-01

    Brain is a morphologically and mechanically heterogeneous organ. Although rat brain is commonly used as an experimental neurophysiological model for various in vivo biomechanical studies, little is known about its regional viscoelastic properties. To address this issue, we have generated viscoelastic mechanical property data for specific anatomical regions of the P17 and adult rat brain. These ages are commonly used in rat experimental models. We measured mechanical properties of both white and gray matter regions in coronal slices with a custom-designed microindentation device performing stress-relaxation indentations to 10% effective strain. Shear moduli calculated for short (100?ms), intermediate (1?sec), and long (20?sec) time points, ranged from ?1?kPa for short term moduli to ?0.4?kPa for long term moduli. Both age and anatomic region were significant factors affecting the time-dependent shear modulus. White matter regions and regions of the cerebellum were much more compliant than those of the hippocampus, cortex, and thalamus. Linear viscoelastic models (Prony series, continuous phase lag, and a power law model) were fit to the time-dependent shear modulus data. All models fit the data equally with no significant differences between them (F-test; p>0.05). The F-test was also used to statistically determine that a Prony series with three time-dependent parameters accurately fit the data with no added benefit from additional terms. The age- and region-dependent rat brain viscoelastic properties presented here will help inform future biomechanical models of the rat brain with specific and accurate regional mechanical property data. PMID:21341982

  14. Functional Neuroanatomy of Executive Function after Neonatal Brain Injury in Adults Who Were Born Very Preterm

    PubMed Central

    Kalpakidou, Anastasia K.; Allin, Matthew P. G.; Walshe, Muriel; Giampietro, Vincent; McGuire, Philip K.; Rifkin, Larry; Murray, Robin M.; Nosarti, Chiara

    2014-01-01

    Individuals who were born very preterm (VPT; <33 gestational weeks) are at risk of experiencing deficits in tasks involving executive function in childhood and beyond. In addition, the type and severity of neonatal brain injury associated with very preterm birth may exert differential effects on executive functioning by altering its neuroanatomical substrates. Here we addressed this question by investigating with functional magnetic resonance imaging (fMRI) the haemodynamic response during executive-type processing using a phonological verbal fluency and a working memory task in VPT-born young adults who had experienced differing degrees of neonatal brain injury. 12 VPT individuals with a history of periventricular haemorrhage and ventricular dilatation (PVH+VD), 17 VPT individuals with a history of uncomplicated periventricular haemorrhage (UPVH), 13 VPT individuals with no history of neonatal brain injury and 17 controls received an MRI scan whilst completing a verbal fluency task with two cognitive loads (‘easy’ and ‘hard’ letters). Two groups of VPT individuals (PVH+VD; n = 10, UPVH; n = 8) performed an n-back task with three cognitive loads (1-, 2-, 3-back). Results demonstrated that VPT individuals displayed hyperactivation in frontal, temporal, and parietal cortices and in caudate nucleus, insula and thalamus compared to controls, as demands of the verbal fluency task increased, regardless of type of neonatal brain injury. On the other hand, during the n-back task and as working memory load increased, the PVH+VD group showed less engagement of the frontal cortex than the UPVH group. In conclusion, this study suggests that the functional neuroanatomy of different executive-type processes is altered following VPT birth and that neural activation associated with specific aspects of executive function (i.e., working memory) may be particularly sensitive to the extent of neonatal brain injury. PMID:25438043

  15. Reading in the brain of children and adults: A meta‐analysis of 40 functional magnetic resonance imaging studies

    PubMed Central

    Martin, Anna; Schurz, Matthias; Kronbichler, Martin

    2015-01-01

    Abstract We used quantitative, coordinate‐based meta‐analysis to objectively synthesize age‐related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23–34 years) were matched to 20 studies with children (age means: 7–12 years). The separate meta‐analyses of these two sets showed a pattern of reading‐related brain activation common to children and adults in left ventral occipito‐temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta‐analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading‐related activation clusters in children and adults are provided. Hum Brain Mapp 36:1963–1981, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25628041

  16. Ribosomal protein L11 is related to brain maturation during the adult phase in Apis cerana cerana (Hymenoptera, Apidae)

    NASA Astrophysics Data System (ADS)

    Meng, Fei; Lu, Wenjing; Yu, Feifei; Kang, Mingjiang; Guo, Xingqi; Xu, Baohua

    2012-05-01

    Ribosomal proteins (RPs) play pivotal roles in developmental regulation. The loss or mutation of ribosomal protein L11 ( RPL11) induces various developmental defects. However, few RPs have been functionally characterized in Apis cerana cerana. In this study, we isolated a single copy gene, AccRPL11, and characterized its connection to brain maturation. AccRPL11 expression was highly concentrated in the adult brain and was significantly induced by abiotic stresses such as pesticides and heavy metals. Immunofluorescence assays demonstrated that AccRPL11 was localized to the medulla, lobula and surrounding tissues of esophagus in the brain. The post-transcriptional knockdown of AccRPL11 gene expression resulted in a severe decrease in adult brain than in other tissues. The expression levels of other brain development-related genes, p38, ERK2, CacyBP and CREB, were also reduced. Immunofluorescence signal attenuation was also observed in AccRPL11-rich regions of the brain in ds AccRPL11-injected honeybees. Taken together, these results suggest that AccRPL11 may be functional in brain maturation in honeybee adults.

  17. 3D Standard Brain of the Red Flour Beetle Tribolium Castaneum: A Tool to Study Metamorphic Development and Adult Plasticity

    PubMed Central

    Dreyer, David; Vitt, Holger; Dippel, Stefan; Goetz, Brigitte; el Jundi, Basil; Kollmann, Martin; Huetteroth, Wolf; Schachtner, Joachim

    2009-01-01

    The red flour beetle Tribolium castaneum is emerging as a further standard insect model beside Drosophila. Its genome is fully sequenced and it is susceptible for genetic manipulations including RNA-interference. We use this beetle to study adult brain development and plasticity primarily with respect to the olfactory system. In the current study, we provide 3D standard brain atlases of freshly eclosed adult female and male beetles (A0). The atlases include eight paired and three unpaired neuropils including antennal lobes (ALs), optic lobe neuropils, mushroom body calyces and pedunculi, and central complex. For each of the two standard brains, we averaged brain areas of 20 individual brains. Additionally, we characterized eight selected olfactory glomeruli from 10 A0 female and male beetles respectively, which we could unequivocally recognize from individual to individual owing to their size and typical position in the ALs. In summary, comparison of the averaged neuropil volumes revealed no sexual dimorphism in any of the reconstructed neuropils in A0 Tribolium brains. Both, the female and male 3D standard brain are also used for interspecies comparisons, and, importantly, will serve as future volumetric references after genetical manipulation especially regarding metamorphic development and adult plasticity. PMID:20339482

  18. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  19. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    PubMed Central

    Richards, Alexander L; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V; Levinson, Douglas F; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M; Craddock, Nick; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C

    2016-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs selected for marginal evidence for association (p<0.5) from genome wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs which are also eQTLs should carry more true association signals compared with SNPs which are not. To test this, we identified marginally associated (p<0.5) SNPs from two of the largest available schizophrenia GWAS datasets. We assigned eQTL status to those SNPs based upon an eQTL dataset derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can in principle allow relevant susceptibility eQTLs to be identified. PMID:21339752

  20. Brain structure and cognitive correlates of body mass index in healthy older adults

    PubMed Central

    Bolzenius, Jacob D.; Laidlaw, David H.; Cabeen, Ryan P.; Conturo, Thomas E.; McMichael, Amanda R.; Lane, Elizabeth M.; Heaps, Jodi M.; Salminen, Lauren E.; Baker, Laurie M.; Scott, Staci E.; Cooley, Sarah A.; Gunstad, John; Paul, Robert H.

    2014-01-01

    Obesity, commonly measured with body mass index (BMI), is associated with numerous deleterious health conditions including alterations in brain integrity related to advanced age. Prior research has suggested that white matter integrity observed using diffusion tensor imaging (DTI) is altered in relation to high BMI, but the integrity of specific white matter tracts remains poorly understood. Additionally, no studies have examined white matter tract integrity in conjunction with neuropsychological evaluation associated with BMI among older adults. The present study examined white matter tract integrity using DTI and cognitive performance associated with BMI in 62 healthy older adults (20 males, 42 females) aged 51 to 81. Results revealed that elevated BMI was associated with lower fractional anisotropy (FA) in the uncinate fasciculus, though there was no evidence of an age by BMI interaction relating to FA in this tract. No relationships were observed between BMI and other white matter tracts or cognition after controlling for demographic variables. Findings suggest that elevated BMI is associated with lower structural integrity in a brain region connecting frontal and temporal lobes and this alteration precedes cognitive dysfunction. Future studies should examine biological mechanisms that mediate the relationships between BMI and white matter tract integrity, as well as the evolution of these abnormalities utilizing longitudinal designs. PMID:25448431

  1. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

    PubMed Central

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R.; Killinger, Bryan A.

    2015-01-01

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum. PMID:26463126

  2. Brain structure and cognitive correlates of body mass index in healthy older adults.

    PubMed

    Bolzenius, Jacob D; Laidlaw, David H; Cabeen, Ryan P; Conturo, Thomas E; McMichael, Amanda R; Lane, Elizabeth M; Heaps, Jodi M; Salminen, Lauren E; Baker, Laurie M; Scott, Staci E; Cooley, Sarah A; Gunstad, John; Paul, Robert H

    2015-02-01

    Obesity, commonly measured with body mass index (BMI), is associated with numerous deleterious health conditions including alterations in brain integrity related to advanced age. Prior research has suggested that white matter integrity observed using diffusion tensor imaging (DTI) is altered in relation to high BMI, but the integrity of specific white matter tracts remains poorly understood. Additionally, no studies have examined white matter tract integrity in conjunction with neuropsychological evaluation associated with BMI among older adults. The present study examined white matter tract integrity using DTI and cognitive performance associated with BMI in 62 healthy older adults (20 males, 42 females) aged 51-81. Results revealed that elevated BMI was associated with lower fractional anisotropy (FA) in the uncinate fasciculus, though there was no evidence of an age by BMI interaction relating to FA in this tract. No relationships were observed between BMI and other white matter tracts or cognition after controlling for demographic variables. Findings suggest that elevated BMI is associated with lower structural integrity in a brain region connecting frontal and temporal lobes and this alteration precedes cognitive dysfunction. Future studies should examine biological mechanisms that mediate the relationships between BMI and white matter tract integrity, as well as the evolution of these abnormalities utilizing longitudinal designs. PMID:25448431

  3. In-vivo RGB marking and multicolour single-cell tracking in the adult brain

    PubMed Central

    Gomez-Nicola, Diego; Riecken, Kristoffer; Fehse, Boris; Perry, V. Hugh

    2014-01-01

    In neuroscience it is a technical challenge to identify and follow the temporal and spatial distribution of cells as they differentiate. We hypothesised that RGB marking, the tagging of individual cells with unique hues resulting from simultaneous expression of the three basic colours red, green and blue, provides a convenient toolbox for the study of the CNS anatomy at the single-cell level. Using γ-retroviral and lentiviral vector sets we describe for the first time the in-vivo multicolour RGB marking of neurons in the adult brain. RGB marking also enabled us to track the spatial and temporal fate of neural stem cells in the adult brain. The application of different viral envelopes and promoters provided a useful approach to track the generation of neurons vs. glial cells at the neurogenic niche, allowing the identification of the prominent generation of new astrocytes to the striatum. Multicolour RGB marking could serve as a universal and reproducible method to study and manipulate the CNS at the single-cell level, in both health and disease. PMID:25531807

  4. Post-independence fledgling ecology in a migratory songbird: Implications for breeding-grounds conservation

    USGS Publications Warehouse

    Streby, H.M.; Peterson, S.M.; Kramer, G.R.; Anderson, D.E.

    2014-01-01

    For migratory songbirds, breeding-grounds conservation and management plans are generally focused on habitat associated with locations of singing males and sometimes nesting females. However, habitat structure is often different in areas used for raising fledglings compared with areas used for song territories, and very little is known about habitat use by fledglings after independence from adult care. From 2010 to 2012, we used radiotelemetry to monitor 68 fledgling golden-winged warblers Vermivora chrysoptera after independence from adult care in mixed managed forests of Minnesota, US and Manitoba, Canada. This species is of high conservation concern in the US, is listed as threatened in Canada and is listed as near threatened on the International Union for Conservation of Nature Red List. We assessed distance and orientation of independent fledgling movements and we used compositional analysis to test for selection among cover types. Fledglings of this species, commonly described as a shrubland specialist, selected mature forest (78% of locations) over all other cover types, and foraged in forest canopy and understory in mixed-species flocks. Fledgling golden-winged warbler movements were apparently associated with habitat optimization (although prioritizing foraging over predator avoidance), and likely not with commencement of migration, or scouting future breeding territories. Ten days after independence, fledglings were an average of 1238 m north of their nest, which may be related to homing-target formation and the species' northward range expansion. We conclude that consideration for independent fledgling habitat associations is necessary for developing full-fledged forest management plans on the breeding grounds of migratory songbirds.

  5. Assessing visual requirements for social context-dependent activation of the songbird song system

    PubMed Central

    Hara, Erina; Kubikova, Lubica; Hessler, Neal A.; Jarvis, Erich D.

    2008-01-01

    Social context has been shown to have a profound influence on brain activation in a wide range of vertebrate species. Best studied in songbirds, when males sing undirected song, the level of neural activity and expression of immediate early genes (IEGs) in several song nuclei is dramatically higher or lower than when they sing directed song to other birds, particularly females. This differential social context-dependent activation is independent of auditory input and is not simply dependent on the motor act of singing. These findings suggested that the critical sensory modality driving social context-dependent differences in the brain could be visual cues. Here, we tested this hypothesis by examining IEG activation in song nuclei in hemispheres to which visual input was normal or blocked. We found that covering one eye blocked visually induced IEG expression throughout both contralateral visual pathways of the brain, and reduced activation of the contralateral ventral tegmental area, a non-visual midbrain motivation-related area affected by social context. However, blocking visual input had no effect on the social context-dependent activation of the contralateral song nuclei during female-directed singing. Our findings suggest that individual sensory modalities are not direct driving forces for the social context differences in song nuclei during singing. Rather, these social context differences in brain activation appear to depend more on the general sense that another individual is present. PMID:18826930

  6. Dawn-song onset coincides with increased HVC androgen receptor expression but is decoupled from high circulating testosterone in an equatorial songbird.

    PubMed

    Quispe, René; Sèbe, Frédéric; da Silva, Maria Luisa; Gahr, Manfred

    2016-03-15

    The song of songbirds is a testosterone-sensitive behavior that is controlled by brain regions expressing androgen receptors. At higher latitudes, seasonal singing is stimulated by increasing day-length and elevated circulating testosterone. However, a large number of songbird species inhabit equatorial regions under a nearly constant photoperiod, and the neuroendocrine mechanisms of seasonal song in these species have rarely been investigated. We studied males from an equatorial population of the silver-beaked tanager (Ramphocelus carbo), an Amazonian songbird. We found seasonality in dawn-song behavior, which was displayed continuously for more than half a year throughout an extended breeding territoriality stage. The seasonal activation of dawn-song was correlated with an increased area of androgen receptor expression in HVC, a major brain area of song control. However, testosterone levels remained low for several weeks after activation of dawn-song. Circulating levels of testosterone were elevated only later in the breeding season, coinciding with a higher dawn-song output and with the mating period. Our results suggest that the seasonal activation of dawn-song and territoriality involves an increase of androgen target cells in HVC. This mechanism could potentially function to circumvent adverse effects of high testosterone levels in a species with an extended breeding season. PMID:26752610

  7. Brain apoptosis signaling pathways are regulated by methylphenidate treatment in young and adult rats.

    PubMed

    Réus, Gislaine Z; Scaini, Giselli; Jeremias, Gabriela C; Furlanetto, Camila B; Morais, Meline O S; Mello-Santos, Lis Maira; Quevedo, João; Streck, Emilio L

    2014-10-01

    Methylphenidate (MPH) is commonly prescribed for children who have been diagnosed with attention deficit hyperactivity disorder (ADHD); however, the action mechanisms of methylphenidate have not been fully elucidated. Studies have shown a relationship between apoptosis signaling pathways and psychiatric disorders, as well as in therapeutic targets for such disorders. So, we investigated if chronic treatment with MPH at doses of 1, 2 and 10mg/kg could alter the levels of pro-apoptotic protein, Bax, anti-apoptotic protein, Bcl-2, caspase-3 and cytochrome c in the brain of young and adult Wistar rats. Our results showed that MPH at all doses increased Bax in the cortex; the Bcl-2 and caspase-3 were increased with MPH (1mg/kg) and were reduced with MPH (2 and 10mg/kg); the cytochrome c was reduced in the cortex after treatment with MPH at all doses; in the cerebellum there was an increase of Bax with MPH at all doses, however, there was a reduction of Bcl-2, caspase-3, and cytochrome c with MPH (2 and 10mg/kg); in the striatum the treatment with MPH (10mg/kg) decreased caspase-3 and cytochrome c; treatment with MPH (2 and 10mg/kg) increased Bax and decreased Bcl-2 in the hippocampus; and the caspase-3 and cytochrome c were reduced in the hippocampus with MPH (10mg/kg). In conclusion, our results suggest that MPH influences plasticity in the brain of young and adult rats; however, the effects were dependent of age and brain area, on the one hand activating the initial cascade of apoptosis, increasing Bax and reducing Bcl-2, but otherwise inhibiting apoptosis by reduction of caspase-3 and cytochrome c. PMID:25128604

  8. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    PubMed Central

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  9. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses

    PubMed Central

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury’s etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care. PMID:27446888

  10. Neurobehavioural treatment for obsessive-compulsive disorder in an adult with traumatic brain injury.

    PubMed

    Arco, Lucius

    2008-01-01

    Although obsessive-compulsive disorder has been reported as one of many anxiety-related sequelae of brain injury, few empirical data of its responsiveness to psychological intervention are available. In this study, a single participant changing criterion experimental design was used to evaluate a neurobehavioural intervention for compulsive behaviour of an adult with severe traumatic brain injury. The participant, a man aged 24 years, had sustained frontal-temporal lobe brain trauma 12 months earlier, and presented with compulsive counting and voiding of bladder. The neurobehavioural intervention consisted of regular in-home consultations, self-regulation procedures including self-recording of compulsive behaviour, stress-coping strategies, errorless remediation, social reinforcement, and gradual fading of intervention. Baseline showed counting occurred on average 80% of daily hourly intervals, and voiding 12 times per day. Intervention produced elimination of compulsive counting, acceptable voiding at 8 times per day, and reports of the participant's satisfaction with intervention methods and outcomes. At 6 months follow-up, counting remained at zero levels, and voiding had decreased further to 7 times per day. PMID:18058389

  11. Self-reported electrical appliance use and risk of adult brain tumors.

    PubMed

    Kleinerman, Ruth A; Linet, Martha S; Hatch, Elizabeth E; Tarone, Robert E; Black, Peter M; Selker, Robert G; Shapiro, William R; Fine, Howard A; Inskip, Peter D

    2005-01-15

    Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors. PMID:15632263

  12. Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Rao, Stephen M.

    2013-01-01

    Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD. PMID:24961307

  13. Vascular health and longitudinal changes in brain and cognition in middle-aged and older adults.

    PubMed

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Acker, James D

    2007-03-01

    The impact of vascular health on the relations between structural brain changes and cognition was assessed in a longitudinal study of 46 adults, 23 of whom remained healthy for 5 years and 23 of whom had hypertension at baseline or acquired vascular problems during follow-up. At both measurement occasions, the volume of white matter hyperintensities (WMH) and regional brain volumes correlated with age. In 5 years, WMH volume more than doubled in the vascular risk group but did not increase in healthy participants. The frontal lobes had the highest WMH load at baseline and follow-up; the parietal WMH showed the greatest rate of expansion. In the vascular risk group, systolic blood pressure at follow-up correlated with posterior WMH volume. The fastest cortical shrinkage was observed in the prefrontal cortex and the hippocampus. Fluid intelligence correlated with WMH burden and declined along with faster WMH progression. In the vascular risk group, WMH progression and shrinkage of the fusiform cortex correlated with decline in working memory. Thus, poor vascular health contributes to age-related declines in brain and cognition, and some of the age-related declines may be limited to persons with elevated vascular risk. PMID:17402815

  14. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses.

    PubMed

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury's etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care. PMID:27446888

  15. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

    PubMed Central

    Barth, Claudia; Villringer, Arno; Sacher, Julia

    2015-01-01

    Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo. PMID:25750611

  16. Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain.

    PubMed

    Kaslin, Jan; Ganz, Julia; Brand, Michael

    2008-01-12

    Post-embryonic neurogenesis is a fundamental feature of the vertebrate brain. However, the level of adult neurogenesis decreases significantly with phylogeny. In the first part of this review, a comparative analysis of adult neurogenesis and its putative roles in vertebrates are discussed. Adult neurogenesis in mammals is restricted to two telencephalic constitutively active zones. On the contrary, non-mammalian vertebrates display a considerable amount of adult neurogenesis in many brain regions. The phylogenetic differences in adult neurogenesis are poorly understood. However, a common feature of vertebrates (fish, amphibians and reptiles) that display a widespread adult neurogenesis is the substantial post-embryonic brain growth in contrast to birds and mammals. It is probable that the adult neurogenesis in fish, frogs and reptiles is related to the coordinated growth of sensory systems and corresponding sensory brain regions. Likewise, neurons are substantially added to the olfactory bulb in smell-oriented mammals in contrast to more visually oriented primates and songbirds, where much fewer neurons are added to the olfactory bulb. The second part of this review focuses on the differences in brain plasticity and regeneration in vertebrates. Interestingly, several recent studies show that neurogenesis is suppressed in the adult mammalian brain. In mammals, neurogenesis can be induced in the constitutively neurogenic brain regions as well as ectopically in response to injury, disease or experimental manipulations. Furthermore, multipotent progenitor cells can be isolated and differentiated in vitro from several otherwise silent regions of the mammalian brain. This indicates that the potential to recruit or generate neurons in non-neurogenic brain areas is not completely lost in mammals. The level of adult neurogenesis in vertebrates correlates with the capacity to regenerate injury, for example fish and amphibians exhibit the most widespread adult neurogenesis

  17. Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

    PubMed Central

    List, Jonathan; Ott, Stefanie; Bukowski, Martin; Lindenberg, Robert; Flöel, Agnes

    2015-01-01

    Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and gray matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI) in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex- and education matched controls with no history of mTBI (control group). All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT) and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials. PMID:26052275

  18. Endogenous brain erythropoietin is a potent sex-specific respiratory stimulant in adult and newborn mice.

    PubMed

    Ballot, Orlane; Joseph, Vincent; Soliz, Jorge

    2015-06-01

    We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency (fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (-25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (-37% in males, -59% in females) and VT (-38% in males, -47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia. PMID:25792712

  19. Expression of Npas4 mRNA in Telencephalic Areas of Adult and Postnatal Mouse Brain

    PubMed Central

    Damborsky, Joanne C.; Slaton, G. Simona; Winzer-Serhan, Ursula H.

    2015-01-01

    The transcription factor neuronal PAS domain-containing protein 4 (Npas4) is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON), piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu), septum and basolateral amygdala nucleus (BLA), basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5), transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission. PMID:26633966

  20. Adult sports-related traumatic brain injury in United States trauma centers.

    PubMed

    Winkler, Ethan A; Yue, John K; Burke, John F; Chan, Andrew K; Dhall, Sanjay S; Berger, Mitchel S; Manley, Geoffrey T; Tarapore, Phiroz E

    2016-04-01

    OBJECTIVE Sports-related traumatic brain injury (TBI) is an important public health concern estimated to affect 300,000 to 3.8 million people annually in the United States. Although injuries to professional athletes dominate the media, this group represents only a small proportion of the overall population. Here, the authors characterize the demographics of sports-related TBI in adults from a community-based trauma population and identify predictors of prolonged hospitalization and increased morbidity and mortality rates. METHODS Utilizing the National Sample Program of the National Trauma Data Bank (NTDB), the authors retrospectively analyzed sports-related TBI data from adults (age ≥ 18 years) across 5 sporting categories-fall or interpersonal contact (FIC), roller sports, skiing/snowboarding, equestrian sports, and aquatic sports. Multivariable regression analysis was used to identify predictors of prolonged hospital length of stay (LOS), medical complications, inpatient mortality rates, and hospital discharge disposition. Statistical significance was assessed at α < 0.05, and the Bonferroni correction for multiple comparisons was applied for each outcome analysis. RESULTS From 2003 to 2012, in total, 4788 adult sports-related TBIs were documented in the NTDB, which represented 18,310 incidents nationally. Equestrian sports were the greatest contributors to sports-related TBI (45.2%). Mild TBI represented nearly 86% of injuries overall. Mean (± SEM) LOSs in the hospital or intensive care unit (ICU) were 4.25 ± 0.09 days and 1.60 ± 0.06 days, respectively. The mortality rate was 3.0% across all patients, but was statistically higher in TBI from roller sports (4.1%) and aquatic sports (7.7%). Age, hypotension on admission to the emergency department (ED), and the severity of head and extracranial injuries were statistically significant predictors of prolonged hospital and ICU LOSs, medical complications, failure to discharge to home, and death. Traumatic

  1. Measuring inhibitory control in children and adults: brain imaging and mental chronometry

    PubMed Central

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., “fast thinking” in Daniel Kahneman’s words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children’s conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need “prefrontal pedagogy” in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks. PMID:24994993

  2. Measuring inhibitory control in children and adults: brain imaging and mental chronometry.

    PubMed

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., "fast thinking" in Daniel Kahneman's words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children's conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need "prefrontal pedagogy" in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks. PMID:24994993

  3. Adult neurogenesis in the crayfish brain: proliferation, migration and possible origin of precursor cells

    PubMed Central

    Zhang, Y.; Allodi, S.; Sandeman, D.C.; Beltz, B.S.

    2015-01-01

    The birth of new neurons and their incorporation into functional circuits in the adult brain is a characteristic of many vertebrate and invertebrate organisms, including decapod crustaceans. Precursor cells maintaining life-long proliferation in the brains of crayfish (Procambarus clarkii, Cherax destructor) and clawed lobsters (Homarus americanus) reside within a specialized niche on the ventral surface of the brain; their daughters migrate to two proliferation zones along a stream formed by processes of the niche precursors. Here they divide again, finally producing interneurons in the olfactory pathway. The present studies in P. clarkii explore (1) differential proliferative activity among the niche precursor cells with growth and aging, (2) morphological characteristics of cells in the niche and migratory streams, and (3) aspects of the cell cycle in this lineage. Morphologically symmetrical divisions of neuronal precursor cells were observed in the niche near where the migratory streams emerge, as well as in the streams and proliferation zones. The nuclei of migrating cells elongate and undergo shape changes consistent with nucleokinetic movement. LIS1, a highly conserved dynein-binding protein, is expressed in cells in the migratory stream and neurogenic niche, implicating this protein in the translocation of crustacean brain neuronal precursor cells. Symmetrical divisions of the niche precursors and migration of both daughters raised the question of how the niche precursor pool is replenished. We present here preliminary evidence for an association between vascular cells and the niche precursors, which may relate to the life-long growth and maintenance of the crustacean neurogenic niche. PMID:19294644

  4. Adult neurogenesis in the crayfish brain: proliferation, migration, and possible origin of precursor cells.

    PubMed

    Zhang, Yi; Allodi, Silvana; Sandeman, David C; Beltz, Barbara S

    2009-06-01

    The birth of new neurons and their incorporation into functional circuits in the adult brain is a characteristic of many vertebrate and invertebrate organisms, including decapod crustaceans. Precursor cells maintaining life-long proliferation in the brains of crayfish (Procambarus clarkii, Cherax destructor) and clawed lobsters (Homarus americanus) reside within a specialized niche on the ventral surface of the brain; their daughters migrate to two proliferation zones along a stream formed by processes of the niche precursors. Here they divide again, finally producing interneurons in the olfactory pathway. The present studies in P. clarkii explore (1) differential proliferative activity among the niche precursor cells with growth and aging, (2) morphological characteristics of cells in the niche and migratory streams, and (3) aspects of the cell cycle in this lineage. Morphologically symmetrical divisions of neuronal precursor cells were observed in the niche near where the migratory streams emerge, as well as in the streams and proliferation zones. The nuclei of migrating cells elongate and undergo shape changes consistent with nucleokinetic movement. LIS1, a highly conserved dynein-binding protein, is expressed in cells in the migratory stream and neurogenic niche, implicating this protein in the translocation of crustacean brain neuronal precursor cells. Symmetrical divisions of the niche precursors and migration of both daughters raised the question of how the niche precursor pool is replenished. We present here preliminary evidence for an association between vascular cells and the niche precursors, which may relate to the life-long growth and maintenance of the crustacean neurogenic niche. PMID:19294644

  5. Trajectories of brain aging in middle-aged and older adults: Regional and individual differences

    PubMed Central

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M.; Kennedy, Kristen M.; Lindenberger, Ulman

    2010-01-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital–frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial–temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEε4 allele exhibited declines not noted in the whole sample. PMID:20298790

  6. Distribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain.

    PubMed

    Lenkei, Z; Palkovits, M; Corvol, P; Llorens-Cortes, C

    1998-02-01

    Angiotensin II and angiotensin III in the brain exert their various effects by acting on two pharmacologically well-defined receptors, the type-1 (AT1) and the type-2 (AT2) receptors. Receptor binding autoradiography has revealed the dominant presence of AT1 in brain nuclei involved in cardiovascular, body fluid and neuroendocrine control. The cloning of the AT1 complementary DNA has revealed the existence of two receptor subtypes in rodents, AT1A and AT1B. Using specific riboprobes for in situ hybridization, we have previously shown that the AT1A messenger RNA is predominantly expressed in the rat forebrain; in contrast the AT1B subtype predominates in the anterior pituitary. Using a similar technical approach, the aim of the present study was to establish the precise anatomical localization of cells synthetising the AT1A receptor in the adult rat brain. High AT1A messenger RNA expression was found in the vascular organ of the lamina terminalis, the median preoptic nucleus, the subfornical organ, the hypothalamic periventricular nucleus, the parvocellular parts of the paraventricular nucleus, the nucleus of the solitary tract and the area postrema, in agreement with previous autoradiographic studies, describing a high density of AT1 binding sites in these nuclei. In addition, AT1A messenger RNA expression was detected in several brain areas, where no AT1 binding was reported previously. Thus, we identify strong expression of AT1A messenger RNA expression in scattered cells of the lateral parts of the preoptic region, the lateral hypothalamus and several brainstem nuclei. In none of these structures was the AT1B messenger RNA detectable at the microscopic level. In conclusion, it is suggested that angiotensins may exert their central effects on body fluid and cardiovascular homeostasis mainly via the AT1A receptor subtype. PMID:9483539

  7. The relation between brain activity during memory tasks and years of education in young and older adults.

    PubMed

    Springer, Mellanie V; McIntosh, Anthony R; Winocur, Gordon; Grady, Cheryl L

    2005-03-01

    Higher education is associated with less age-related decline in cognitive function, but the mechanism of this protective effect is unknown. The authors examined the effect of age on the relation between education and brain activity by correlating years of education with activity measured using functional MRI during memory tasks in young and older adults. In young adults, education was negatively correlated with frontal activity, whereas in older adults, education was positively correlated with frontal activity. Medial temporal activity was associated with more education in young adults but less education in older adults. This suggests that the frontal cortex is engaged by older adults, particularly by the highly educated, as an alternative network that may be engaged to aid cognitive function. PMID:15769202

  8. Structural alterations of brain grey and white matter in early deaf adults.

    PubMed

    Hribar, Manja; Suput, Dušan; Carvalho, Altiere Araujo; Battelino, Saba; Vovk, Andrej

    2014-12-01

    Functional and structural brain alterations in the absence of the auditory input have been described, but the observed structural brain changes in the deaf are not uniform. Some of the previous researchers focused only on the auditory areas, while others investigated the whole brain or other selected regions of interest. Majority of studies revealed decreased white matter (WM) volume or altered WM microstructure and preserved grey matter (GM) structure of the auditory areas in the deaf. However, preserved WM and increased or decreased GM volume of the auditory areas in the deaf have also been reported. Several structural alterations in the deaf were found also outside the auditory areas, but these regions differ between the studies. The observed differences between the studies could be due to the use of different single-analysis techniques, or the diverse population sample and its size, or possibly due to the usage of hearing aids by some participating deaf subjects. To overcome the aforementioned limitations four different image-processing techniques were used to investigate changes in the brain morphology of prelingually deaf adults who have never used hearing aids. GM and WM volume of the Heschl's gyrus (HG) were measured using manual volumetry, while whole brain GM volume, thickness and surface area were assessed by voxel-based morphometry (VBM) and surface-based analysis. The microstructural properties of the WM were evaluated by diffusion tensor imaging (DTI). The data were compared between 14 congenitally deaf adults and 14 sex- and age-matched normal hearing controls. Manual volumetry revealed preserved GM volume of the bilateral HG and significantly decreased WM volume of the left HG in the deaf. VBM showed increased cerebellar GM volume in the deaf, while no statistically significant differences were observed in the GM thickness or surface area between the groups. The results of the DTI analysis showed WM microstructural alterations between the groups in

  9. Models of vocal learning in the songbird: Historical frameworks and the stabilizing critic.

    PubMed

    Nick, Teresa A

    2015-10-01

    Birdsong is a form of sensorimotor learning that involves a mirror-like system that activates with both song hearing and production. Early models of song learning, based on behavioral measures, identified key features of vocal plasticity, such as the requirements for memorization of a tutor song and auditory feedback during song practice. The concept of a comparator, which compares the memory of the tutor song to auditory feedback, featured prominently. Later models focused on linking anatomically-defined neural modules to behavioral concepts, such as the comparator. Exploiting the anatomical modularity of the songbird brain, localized lesions illuminated mechanisms of the neural song system. More recent models have integrated neuronal mechanisms identified in other systems with observations in songbirds. While these models explain multiple aspects of song learning, they must incorporate computational elements based on unknown biological mechanisms to bridge the motor-to-sensory delay and/or transform motor signals into the sensory domain. Here, I introduce the stabilizing critic hypothesis, which enables sensorimotor learning by (1) placing a purely sensory comparator afferent of the song system and (2) endowing song system disinhibitory interneuron networks with the capacity both to bridge the motor-sensory delay through prolonged bursting and to stabilize song segments selectively based on the comparator signal. These proposed networks stabilize an otherwise variable signal generated by both putative mirror neurons and a cortical-basal ganglia-thalamic loop. This stabilized signal then temporally converges with a matched premotor signal in the efferent song motor cortex, promoting spike-timing-dependent plasticity in the premotor circuitry and behavioral song learning. PMID:24841478

  10. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults

    PubMed Central

    Burzynska, Agnieszka Z.; Wong, Chelsea N.; Voss, Michelle W.; Cooke, Gillian E.; Gothe, Neha P.; Fanning, Jason; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60–80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  11. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults.

    PubMed

    Burzynska, Agnieszka Z; Wong, Chelsea N; Voss, Michelle W; Cooke, Gillian E; Gothe, Neha P; Fanning, Jason; McAuley, Edward; Kramer, Arthur F

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60-80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  12. New Hippocampal Neurons Are Not Obligatory for Memory Formation; Cyclin D2 Knockout Mice with No Adult Brain Neurogenesis Show Learning

    ERIC Educational Resources Information Center

    Jaholkowski, Piotr; Kiryk, Anna; Jedynak, Paulina; Abdallah, Nada M. Ben; Knapska, Ewelina; Kowalczyk, Anna; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Figiel, Izabela; Lioudyno, Victoria; Widy-Tyszkiewicz, Ewa; Wilczynski, Grzegorz M.; Lipp, Hans-Peter; Kaczmarek, Leszek; Filipkowski, Robert K.

    2009-01-01

    The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs…

  13. Transsynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity

    PubMed Central

    Brenowitz, Eliot A.

    2014-01-01

    The avian song control system provides an excellent model for studying transsynaptic trophic effects of steroid sex hormones. Seasonal changes in systemic testosterone (T) and its metabolites regulate plasticity of this system. Steroids interact with the neurotrophin brain-derived neurotrophic factor (BDNF) to influence cellular processes of plasticity in nucleus HVC of adult birds, including the addition of newborn neurons. This interaction may also occur transsynpatically; T increases the synthesis of BDNF in HVC, and BDNF protein is then released by HVC neurons on to postsynaptic cells in nucleus RA where it has trophic effects on activity and morphology. Androgen action on RA neurons increases their activity and this has a retrograde trophic effect on the addition of new neurons to HVC. The functional linkage of sex steroids to BDNF may be of adaptive value in regulating the trophic effects of the neurotrophin and coordinating circuit function in reproductively relevant contexts. PMID:25285401

  14. Stability and Autolysis of Cortical Neurons in Post-Mortem Adult Rat Brains

    PubMed Central

    Sheleg, Sergey V; LoBello, Janine R; Hixon, Hugh; Coons, Stephen W; Lowry, David; Nedzved, Mikhail K

    2008-01-01

    We investigated the dynamics of autolytic damage of the cortical neurons in adult brains for 24 hours at room temperature (+20°C) after cardiac arrest. The progressive histological and ultrastructural changes were documented using routine and immunohistochemical staining as well as electron microscopy. Our results demonstrated that there were no autolytic damages in the ultrastructure of cerebral neurons in the first 6 hours after warm cardiac arrest, in agreement with previous studies in other mammals. Interestingly, the activation of caspase-3 was observed in a significant number of neurons of the cerebellum and neocortex 9 hours following cardiac arrest. No significant changes related to autolysis were observed using amnio-cupric acid and Nissl (thionine) staining. PMID:18784829

  15. Computer-based cognitive retraining for adults with chronic acquired brain injury: a pilot study.

    PubMed

    Li, Kitsum; Robertson, Julie; Ramos, Joshua; Gella, Stephanie

    2013-10-01

    This study evaluated the effectiveness of a computer-based cognitive retraining (CBCR) program on improving memory and attention deficits in individuals with a chronic acquired brain injury (ABI). Twelve adults with a chronic ABI demonstrating deficits in memory and attention were recruited from a convenience sample from the community. Using a quasi-experimental one-group pretest-posttest design, a significant improvement was found in both memory and attention scores postintervention using the cognitive screening tool. This study supported the effectiveness of CBCR programs in improving cognitive deficits in memory and attention in individuals with chronic ABI. Further research is recommended to validate these findings with a larger ABI population and to investigate transfer to improvement in occupational performance that supports daily living skills. PMID:24102589

  16. Brain-derived neurotrophic factor prevents dendritic retraction of adult mouse retinal ganglion cells.

    PubMed

    Binley, Kate E; Ng, Wai S; Barde, Yves-Alain; Song, Bing; Morgan, James E

    2016-08-01

    We used cultured adult mouse retinae as a model system to follow and quantify the retraction of dendrites using diolistic labelling of retinal ganglion cells (RGCs) following explantation. Cell death was monitored in parallel by nuclear staining as 'labelling' with RGC and apoptotic markers was inconsistent and exceedingly difficult to quantify reliably. Nuclear staining allowed us to delineate a lengthy time window during which dendrite retraction can be monitored in the absence of RGC death. The addition of brain-derived neurotrophic factor (BDNF) produced a marked reduction in dendritic degeneration, even when application was delayed for 3 days after retinal explantation. These results suggest that the delayed addition of trophic factors may be functionally beneficial before the loss of cell bodies in the course of conditions such as glaucoma. PMID:27285957

  17. Using temperature to analyse temporal dynamics in the songbird motor pathway.

    PubMed

    Long, Michael A; Fee, Michale S

    2008-11-13

    Many complex behaviours, like speech or music, have a hierarchical organization with structure on many timescales, but it is not known how the brain controls the timing of behavioural sequences, or whether different circuits control different timescales of the behaviour. Here we address these issues by using temperature to manipulate the biophysical dynamics in different regions of the songbird forebrain involved in song production. We find that cooling the premotor nucleus HVC (formerly known as the high vocal centre) slows song speed across all timescales by up to 45 per cent but only slightly alters the acoustic structure, whereas cooling the downstream motor nucleus RA (robust nucleus of the arcopallium) has no observable effect on song timing. Our observations suggest that dynamics within HVC are involved in the control of song timing, perhaps through a chain-like organization. Local manipulation of brain temperature should be broadly applicable to the identification of neural circuitry that controls the timing of behavioural sequences and, more generally, to the study of the origin and role of oscillatory and other forms of brain dynamics in neural systems. PMID:19005546

  18. Environmental enrichment influences neuronal stem cells in the adult crayfish brain

    PubMed Central

    Ayub, Neishay; Benton, Jeanne L.; Zhang, Yi; Beltz, Barbara S.

    2011-01-01

    New neurons are incorporated throughout life into the brains of many vertebrate and non-vertebrate species. This process of adult neurogenesis is regulated by a variety of external and endogenous factors, including environmental enrichment, which increases the production of neurons in juvenile mice and crayfish. The primary goal of the present study was to exploit the spatial separation of the neuronal precursor cell lineage in crayfish to determine which generation(s) of precursors is altered by environmental conditions. Further, in crayfish, an intimate relationship between the 1st generation neuronal precursors (stem cells) and cells circulating in the hemolymph has been proposed (Zhang et al., 2009). Therefore, a second goal was to assess whether environmental enrichment alters the numbers or types of cells circulating in the hemolymph. We find that neurogenesis in the brains of sexually differentiated procambarid crayfish is enhanced by environmental enrichment as previously demonstrated by Sandeman and Sandeman (2000) in young, sexually undifferentiated Cherax destructor. We also show that environmental enrichment increases the cell cycle rate of neuronal stem cells. While there was no effect of environment on the overall numbers of cells circulating in the hemolymph, enrichment resulted in increased expression of glutamine synthetase, a marker of the neuronal stem cells, in a small percentage of circulating cells; there was little or no expression of this enzyme in hemolymph cells extracted from deprived animals. Thus, environmental enrichment influences the rate of neuronal stem cell division in adult crayfish, as well as the composition of cells circulating in the hemolymph. PMID:21485010

  19. Dairy intake is associated with brain glutathione concentration in older adults123

    PubMed Central

    Lee, Phil; Denney, Douglas R; Spaeth, Kendra; Nast, Olivia; Ptomey, Lauren; Roth, Alexandra K; Lierman, Jo Ann; Sullivan, Debra K

    2015-01-01

    Background: A reduction in key antioxidants such as glutathione has been noted in brain tissue undergoing oxidative stress in aging and neurodegeneration. To date, no dietary factor has been linked to a higher glutathione concentration. However, in an earlier pilot study, we showed evidence of a positive association between cerebral glutathione and dairy intake. Objective: We tested the hypothesis that dairy food consumption is associated with cerebral glutathione concentrations in older adults. Design: In this observational study, we measured cerebral glutathione concentrations in 60 healthy subjects (mean ± SD age: 68.7 ± 6.2 y) whose routine dairy intakes varied. Glutathione concentrations were measured by using a unique, noninvasive magnetic resonance chemical shift imaging technique at 3 T and compared with dairy intakes reported in 7-d food records. Results: Glutathione concentrations in the frontal [Spearman's rank-order correlation (rs) = 0.39, P = 0.013], parietal (rs = 0.50, P = 0.001), and frontoparietal regions (rs = 0.47, P = 0.003) were correlated with average daily dairy servings. In particular, glutathione concentrations in all 3 regions were positively correlated with milk servings (P ≤ 0.013), and those in the parietal region were also correlated with cheese servings (P = 0.015) and calcium intake (P = 0.039). Dairy intake was related to sex, fat-free mass, and daily intakes of energy, protein, and carbohydrates. However, when these factors were controlled through a partial correlation, correlations between glutathione concentrations and dairy and milk servings remained significant. Conclusions: Higher cerebral glutathione concentrations were associated with greater dairy consumption in older adults. One possible explanation for this association is that dairy foods may serve as a good source of substrates for glutathione synthesis in the human brain. PMID:25646325

  20. Gender, intoxication and the developing brain: Problematisations of drinking among young adults in Australian alcohol policy.

    PubMed

    Manton, Elizabeth; Moore, David

    2016-05-01

    In this article, we draw on recent scholarly work in the poststructuralist analysis of policy to consider how policy itself functions as a key site in the constitution of alcohol 'problems', and the political implications of these problematisations. We do this by examining Australian alcohol policy as it relates to young adults (18-24 years old). Our critical analysis focuses on three national alcohol policies (1990, 2001 and 2006) and two Victorian state alcohol policies (2008 and 2013), which together span a 25-year period. We argue that Australian alcohol policies have conspicuously ignored young adult men, despite their ongoing over-representation in the statistical 'evidence base' on alcohol-related harm, while increasingly problematising alcohol consumption amongst other population subgroups. We also identify the development of a new problem representation in Australian alcohol policy, that of 'intoxication' as the leading cause of alcohol-related harm and rising hospital admissions, and argue that changes in the classification and diagnosis of intoxication may have contributed to its prioritisation and problematisation in alcohol policy at the expense of other forms of harm. Finally, we draw attention to how preliminary and inconclusive research on the purported association between binge drinking and brain development in those under 25 years old has been mobilised prematurely to support calls to increase the legal purchasing age from 18 to 21 years. Our critical analysis of the treatment of these three issues - gender, intoxication, and brain development - is intended to highlight the ways in which policy functions as a key site in the constitution of alcohol 'problems'. PMID:26644026

  1. Striatal FoxP2 Is Actively Regulated during Songbird Sensorimotor Learning

    PubMed Central

    Teramitsu, Ikuko; Poopatanapong, Amy; Torrisi, Salvatore; White, Stephanie A.

    2010-01-01

    Background Mutations in the FOXP2 transcription factor lead to language disorders with developmental onset. Accompanying structural abnormalities in cortico-striatal circuitry indicate that at least a portion of the behavioral phenotype is due to organizational deficits. We previously found parallel FoxP2 expression patterns in human and songbird cortico/pallio-striatal circuits important for learned vocalizations, suggesting that FoxP2's function in birdsong may generalize to speech. Methodology/Principal Findings We used zebra finches to address the question of whether FoxP2 is additionally important in the post-organizational function of these circuits. In both humans and songbirds, vocal learning depends on auditory guidance to achieve and maintain optimal vocal output. We tested whether deafening prior to or during the sensorimotor phase of song learning disrupted FoxP2 expression in song circuitry. As expected, the songs of deafened juveniles were abnormal, however basal FoxP2 levels were unaffected. In contrast, when hearing or deaf juveniles sang for two hours in the morning, FoxP2 was acutely down-regulated in the striatal song nucleus, area X. The extent of down-regulation was similar between hearing and deaf birds. Interestingly, levels of FoxP2 and singing were correlated only in hearing birds. Conclusions/Significance Hearing appears to link FoxP2 levels to the amount of vocal practice. As juvenile birds spent more time practicing than did adults, their FoxP2 levels are likely to be low more often. Behaviorally-driven reductions in the mRNA encoding this transcription factor could ultimately affect downstream molecules that function in vocal exploration, especially during sensorimotor learning. PMID:20062527

  2. Songbirds use spectral shape, not pitch, for sound pattern recognition

    PubMed Central

    Bregman, Micah R.; Patel, Aniruddh D.; Gentner, Timothy Q.

    2016-01-01

    Humans easily recognize “transposed” musical melodies shifted up or down in log frequency. Surprisingly, songbirds seem to lack this capacity, although they can learn to recognize human melodies and use complex acoustic sequences for communication. Decades of research have led to the widespread belief that songbirds, unlike humans, are strongly biased to use absolute pitch (AP) in melody recognition. This work relies almost exclusively on acoustically simple stimuli that may belie sensitivities to more complex spectral features. Here, we investigate melody recognition in a species of songbird, the European Starling (Sturnus vulgaris), using tone sequences that vary in both pitch and timbre. We find that small manipulations altering either pitch or timbre independently can drive melody recognition to chance, suggesting that both percepts are poor descriptors of the perceptual cues used by birds for this task. Instead we show that melody recognition can generalize even in the absence of pitch, as long as the spectral shapes of the constituent tones are preserved. These results challenge conventional views regarding the use of pitch cues in nonhuman auditory sequence recognition. PMID:26811447

  3. Songbirds use spectral shape, not pitch, for sound pattern recognition.

    PubMed

    Bregman, Micah R; Patel, Aniruddh D; Gentner, Timothy Q

    2016-02-01

    Humans easily recognize "transposed" musical melodies shifted up or down in log frequency. Surprisingly, songbirds seem to lack this capacity, although they can learn to recognize human melodies and use complex acoustic sequences for communication. Decades of research have led to the widespread belief that songbirds, unlike humans, are strongly biased to use absolute pitch (AP) in melody recognition. This work relies almost exclusively on acoustically simple stimuli that may belie sensitivities to more complex spectral features. Here, we investigate melody recognition in a species of songbird, the European Starling (Sturnus vulgaris), using tone sequences that vary in both pitch and timbre. We find that small manipulations altering either pitch or timbre independently can drive melody recognition to chance, suggesting that both percepts are poor descriptors of the perceptual cues used by birds for this task. Instead we show that melody recognition can generalize even in the absence of pitch, as long as the spectral shapes of the constituent tones are preserved. These results challenge conventional views regarding the use of pitch cues in nonhuman auditory sequence recognition. PMID:26811447

  4. MRI-guided stereotaxic brain surgery in the infant and adult common marmoset.

    PubMed

    Mundinano, Inaki-Carril; Flecknell, Paul A; Bourne, James A

    2016-07-01

    In the past decade, the New World common marmoset (Callithrix jacchus) has taken a seminal position in neurobiological research, fueled in part by its smooth cortical sheet, which allows cortical areas to be easily accessed by current technologies on the dorsal surface of the brain. In this protocol, we describe a method for the precision placement of agents (e.g., tracers or neurotoxins) into small brain regions of the infant and adult marmoset, using an MRI-guided approach. This strategy uses a protocol for prolonged anesthesia without the need for intubation that we have recently developed, alongside appropriate analgesia and monitoring. The protocol can be readily adapted to be used together with advanced research techniques, such as two-photon microscopy and optical imaging. Including a 5-d postoperative care plan, this protocol takes 7 d to complete. The protocol requires a team of personnel experienced in marmoset care and handling, and small-animal neurosurgery; an assistant for monitoring the animal and assisting with anesthesia; and an MRI technician. PMID:27336707

  5. Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains

    PubMed Central

    Zhao, Xinxiang; Pu, Jun; Fan, Yaodong; Niu, Xiaoqun; Yu, Danping; Zhang, Yanglin

    2013-01-01

    Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum (splenium and genu) as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4–8 years. Results showed no laterality ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the splenium of corpus callosum in the white matter, followed by genu of the corpus callosum and the posterior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4–8-year-old rhesus monkeys are similar to those of healthy young people. PMID:25206616

  6. Figurative language processing after traumatic brain injury in adults: a preliminary study.

    PubMed

    Yang, Fanpei Gloria; Fuller, Jerome; Khodaparast, Navid; Krawczyk, Daniel C

    2010-06-01

    Figurative speech (e.g., proverb, irony, metaphor, and idiom) has been reported to be particularly sensitive to measurement of abstract thinking in patients who suffer from impaired abstraction and language abilities. Metaphor processing was investigated with fMRI in adults with moderate to severe post-acute traumatic brain injury (TBI) and healthy age-matched controls using a valence-judgment task. We hypothesized that TBI patients would display decreased activation of the left inferior frontal gyrus (LIFG), which is considered central to semantic memory retrieval and abstract thought, in comparison with healthy controls. We also predicted that decreased activation in TBI individuals would correlate with their behavioral response times. A whole-brain analysis across the two participant groups revealed that patients did not strongly engage frontal and temporal regions related to semantic processing for novel metaphor comprehension, whereas control participants exhibited more intensive and concentrated activation within frontal and temporal areas. A region of interest (ROI) analysis verified that the LIFG was underactivated in TBI patients compared to controls across all conditions. TBI patients' impaired abstraction of novel stimuli may stem from reduced prefrontal control of semantic memory as well as disrupted interconnectivity of prefrontal cortex with other regions. PMID:20230844

  7. Competence in Caregivers of Adolescent and Young Adult Childhood Brain Tumor Survivors

    PubMed Central

    Deatrick, Janet A.; Hobbie, Wendy; Ogle, Sue; Fisher, Michael J.; Barakat, Lamia; Hardie, Thomas; Reilly, Maureen; Li, Yimei; Ginsberg, Jill P.

    2015-01-01

    Objective Caregivers of adolescents and young adults (AYA) with complex medical conditions, including brain tumor survivors, have protracted and often complex roles, yet a gap exists in understanding their perceived competence. The aim of this study is to test a hypothesized model based on the theoretical and empirical literature: better caregiver health, better survivor health, and better family functioning contribute directly to fewer caregiving demands, which in turn contribute to greater caregiver competence. Method Telephone interviews using structured self-report questionnaires were conducted in this cross-sectional study with a sample of 186 caregivers (mothers) of childhood brain tumor survivors aged 14–40 years old who live with at least one parent. Structural equation modeling (SEM) was used to test the hypothesized model. Results The final SEM model suggests that survivor health and family functioning directly predict caregiver competence. Caregiver health indirectly predicts caregiver competence through caregiver demands and then family functioning. Family income directly predicts family functioning. The model showed adequate fit (CFI = 0.905, TFI = 0.880, and RMSEA = 0.081). Overall, the model accounted for 45% of variance in caregiver competence. Conclusions For this sample of caregivers of AYA with medically complex conditions, family functioning and the health of survivors are both important to how they evaluate their skills as caregivers. The results of this study underscore the crucial role of care models that focus on optimizing the health of the survivor, caregiver, and family, along with supporting a family centered approach to their care. PMID:23957900

  8. Adult axolotls can regenerate original neuronal diversity in response to brain injury

    PubMed Central

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. DOI: http://dx.doi.org/10.7554/eLife.13998.001 PMID:27156560

  9. Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

    PubMed

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-01-15

    Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace. PMID:26433146

  10. FGF-2 regulation of neurogenesis in adult hippocampus after brain injury

    PubMed Central

    Yoshimura, Shinichi; Takagi, Yasushi; Harada, Jun; Teramoto, Tetsuyuki; Thomas, Sunu S.; Waeber, Christian; Bakowska, Joanna C.; Breakefield, Xandra O.; Moskowitz, Michael A.

    2001-01-01

    Fibroblast growth factor-2 (FGF-2) promotes proliferation of neuroprogenitor cells in culture and is up-regulated within brain after injury. Using mice genetically deficient in FGF-2 (FGF-2−/− mice), we addressed the importance of endogenously generated FGF-2 on neurogenesis within the hippocampus, a structure involved in spatial, declarative, and contextual memory, after seizures or ischemic injury. BrdUrd incorporation was used to mark dividing neuroprogenitor cells and NeuN expression to monitor their differentiation into neurons. In the wild-type strain, hippocampal FGF-2 increased after either kainic acid injection or middle cerebral artery occlusion, and the numbers of BrdUrd/NeuN-positive cells significantly increased on days 9 and 16 as compared with the controls. In FGF-2−/− mice, BrdUrd labeling was attenuated after kainic acid or middle cerebral artery occlusion, as was the number of neural cells colabeled with both BrdUrd and NeuN. After FGF-2−/− mice were injected intraventricularly with a herpes simplex virus-1 amplicon vector carrying FGF-2 gene, the number of BrdUrd-labeled cells increased significantly to values equivalent to wild-type littermates after kainate seizures. These results indicate that endogenously synthesized FGF-2 is necessary and sufficient to stimulate proliferation and differentiation of neuroprogenitor cells in the adult hippocampus after brain insult. PMID:11320217

  11. The Wechsler Adult Intelligence Scale-III and Malingering in Traumatic Brain Injury: Classification Accuracy in Known Groups

    ERIC Educational Resources Information Center

    Curtis, Kelly L.; Greve, Kevin W.; Bianchini, Kevin J.

    2009-01-01

    A known-groups design was used to determine the classification accuracy of Wechsler Adult Intelligence Scale-III (WAIS-III) variables in detecting malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI). TBI patients were classified into the following groups: (a) mild TBI not-MND (n = 26), (b) mild TBI MND (n = 31), and (c)…

  12. Brain Activity in Adults Who Stutter: Similarities across Speaking Tasks and Correlations with Stuttering Frequency and Speaking Rate

    ERIC Educational Resources Information Center

    Ingham, Roger J.; Grafton, Scott T.; Bothe, Anne K.; Ingham, Janis C.

    2012-01-01

    Many differences in brain activity have been reported between persons who stutter (PWS) and typically fluent controls during oral reading tasks. An earlier meta-analysis of imaging studies identified stutter-related regions, but recent studies report less agreement with those regions. A PET study on adult dextral PWS (n = 18) and matched fluent…

  13. Atypical Brain Activation during Simple & Complex Levels of Processing in Adult ADHD: An fMRI Study

    ERIC Educational Resources Information Center

    Hale, T. Sigi; Bookheimer, Susan; McGough, James J.; Phillips, Joseph M.; McCracken, James T.

    2007-01-01

    Objective: Executive dysfunction in ADHD is well supported. However, recent studies suggest that more fundamental impairments may be contributing. We assessed brain function in adults with ADHD during simple and complex forms of processing. Method: We used functional magnetic resonance imaging with forward and backward digit spans to investigate…

  14. Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults

    PubMed Central

    Buchman, Aron S.; Yu, Lei; Wilson, Robert S.; Dawe, Robert J.; VanderHorst, Veronique; Schneider, Julie A.; Bennett, David A.

    2015-01-01

    Damage to brain structures which constitute the distributed neural network that integrates respiratory muscle and pulmonary functions, can impair adequate ventilation and its volitional control. We tested the hypothesis that the level of brain pathology in older adults is associated with declining respiratory function measured during life. 1,409 older adults had annual testing with spirometry (SPI) and respiratory muscle strength (RMS) based on maximal inspiratory and maximal expiratory pressures (MEPs). Those who died underwent structured brain autopsy. On average, during 5 years of follow-up, SPI and RMS showed progressive decline which was moderately correlated (ρ = 0.57, p < 0.001). Among decedents (N = 447), indices of brain neuropathologies showed differential associations with declining SPI and RMS. Nigral neuronal loss was associated with the person-specific decline in SPI (Estimate, −0.016 unit/year, S.E. 0.006, p = 0.009) and reduction of the slope variance was equal to 4%. By contrast, Alzheimer’s disease (AD) pathology (Estimate, −0.030 unit/year, S.E. 0.009, p < 0.001) and macroscopic infarcts (−0.033 unit/year, S.E., 0.011, p = 0.003) were associated with the person-specific decline in RMS and reduction of the slope variance was equal to 7%. These results suggest that brain pathology is associated with the rate of declining respiratory function in older adults. PMID:26539108

  15. Comparison of specific absorption rate induced in brain tissues of a child and an adult using mobile phone

    NASA Astrophysics Data System (ADS)

    Lu, Mai; Ueno, Shoogo

    2012-04-01

    The steady increase of mobile phone usage, especially mobile phones by children, has led to a rising concern about the possible adverse health effects of radio frequency electromagnetic field exposure. The objective of this work is to study whether there is a larger radio frequency energy absorption in the brain of a child compared to that of an adult. For this reason, three high-resolution models, two child head models (6 - and 11-year old) and one adult head model (34-year old) have been used in the study. A finite-difference time-domain method was employed to calculate the specific absorption rate (SAR) in the models from exposure to a generic handset at 1750 MHz. The results show that the SAR distributions in the human brain are age-dependent, and there is a deeper penetration of the absorbed SAR in the child's brain. The induced SAR can be significantly higher in subregions of the child's brain. In all of the examined cases, the SAR values in the brains of a child and an adult are well below the IEEE safety standard.

  16. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults

    PubMed Central

    Virtanen, J K.; Siscovick, D S.; Longstreth, W T.; Kuller, L H.; Mozaffarian, D

    2008-01-01

    Objective: To investigate the association between fish consumption and subclinical brain abnormalities. Methods: In the population-based Cardiovascular Health Study, 3,660 participants age ≥65 underwent an MRI scan in 1992–1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. Results: After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish ≥3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54–1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Conclusions: Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits. GLOSSARY ARR = absolute risk reduction; BMI = body mass index; CHD = coronary heart disease; CHS = Cardiovascular Health Study; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FFQ = food frequency questionnaire; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; PUFA = polyunsaturated fatty acid; RR = relative risk. PMID:18678827

  17. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    PubMed

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized. PMID:26364049

  18. Stab wound injury of the zebrafish adult telencephalon: a method to investigate vertebrate brain neurogenesis and regeneration.

    PubMed

    Schmidt, Rebecca; Beil, Tanja; Strähle, Uwe; Rastegar, Sepand

    2014-01-01

    Adult zebrafish have an amazing capacity to regenerate their central nervous system after injury. To investigate the cellular response and the molecular mechanisms involved in zebrafish adult central nervous system (CNS) regeneration and repair, we developed a zebrafish model of adult telencephalic injury. In this approach, we manually generate an injury by pushing an insulin syringe needle into the zebrafish adult telencephalon. At different post injury days, fish are sacrificed, their brains are dissected out and stained by immunohistochemistry and/or in situ hybridization (ISH) with appropriate markers to observe cell proliferation, gliogenesis, and neurogenesis. The contralateral unlesioned hemisphere serves as an internal control. This method combined for example with RNA deep sequencing can help to screen for new genes with a role in zebrafish adult telencephalon neurogenesis, regeneration, and repair. PMID:25146302

  19. Neuroprotective Pathways: Lifestyle activity, brain pathology and cognition in cognitively normal older adults

    PubMed Central

    Wirth, Miranka; Haase, Claudia M.; Villeneuve, Sylvia; Vogel, Jacob; Jagust, William J.

    2014-01-01

    This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within brain regions affected in Alzheimer’s disease (AD). Ninety-two cognitively normal older adults (75.2±5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using PIB-PET), cerebrovascular lesions (using MRI-defined white matter lesion (WML)), and neural integrity within AD regions (using a multimodal biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower PIB retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development. PMID:24656834

  20. Differential vascular permeability along the forebrain ventricular neurogenic niche in the adult murine brain.

    PubMed

    Colín-Castelán, Dannia; Ramírez-Santos, Jesús; Gutiérrez-Ospina, Gabriel

    2016-02-01

    Adult neurogenesis is influenced by blood-borne factors. In this context, greater or lesser vascular permeability along neurogenic niches would expose differentially neural stem cells (NSCs), transit amplifying cells (TACs), and neuroblasts to such factors. Here we evaluate endothelial cell morphology and vascular permeability along the forebrain neurogenic niche in the adult brain. Our results confirm that the subventricular zone (SVZ) contains highly permeable, discontinuous blood vessels, some of which allow the extravasation of molecules larger than those previously reported. In contrast, the rostral migratory stream (RMS) and the olfactory bulb core (OBc) display mostly impermeable, continuous blood vessels. These results imply that NSCs, TACs, and neuroblasts located within the SVZ are exposed more readily to blood-borne molecules, including those with very high molecular weights, than those positioned along the RMS and the OBc, subregions in which every stage of neurogenesis also takes place. These observations suggest that the existence of specialized vascular niches is not a precondition for neurogenesis to occur; specialized vascular beds might be essential for keeping high rates of proliferation and/or differential differentiation of neural precursors located at distinct domains. PMID:26492830

  1. Longitudinal Alterations to Brain Function, Structure, and Cognitive Performance in Healthy Older Adults: a fMRI-DTI study

    PubMed Central

    Hakun, Jonathan G.; Zhu, Zude; Brown, Christopher A.; Johnson, Nathan F.; Gold, Brian T.

    2015-01-01

    Cross-sectional research has shown that older adults tend to have different frontal cortex activation patterns, poorer brain structure, and lower task performance than younger adults. However, relationships between longitudinal changes in brain function, brain structure, and cognitive performance in older adults are less well understood. Here we present the results of a longitudinal, combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point study was conducted in which participants completed a task switching paradigm while fMRI data was collected and underwent the identical scanning protocol an average of 3.3 years later (SD = 2 months). We observed longitudinal fMRI activation increases in bilateral regions of lateral frontal cortex at time point 2. These fMRI activation increases were associated with longitudinal declines in WM microstructure in a portion of the corpus callosum connecting the increasingly recruited frontal regions. In addition, the fMRI activation increase in the left VLPFC was associated with longitudinal increases in response latencies. Taken together, our results suggest that local frontal activation increases in CN older adults may in part reflect a response to reduced inter-hemispheric signaling mechanisms. PMID:25862416

  2. Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies

    PubMed Central

    Zhang, Jiaxing; Zhang, Haiyan; Li, Jinqiang; Chen, Ji; Han, Qiaoqing; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2013-01-01

    The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20–22 years) who immigrated to the Qinghai-Tibet Plateau (2300–4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits. PMID:23874692

  3. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

    PubMed Central

    Bergey, Gregory K.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E.; Shields, Donald C.; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S.; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M.; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B.; Hirsch, Lawrence J.; Courtney, Tracy; Sun, Felice T.; Seale, Cairn G.

    2015-01-01

    Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. PMID:25616485

  4. Age-specific MRI brain and head templates for healthy adults from 20 through 89 years of age

    PubMed Central

    Fillmore, Paul T.; Phillips-Meek, Michelle C.; Richards, John E.

    2015-01-01

    This study created and tested a database of adult, age-specific MRI brain and head templates. The participants included healthy adults from 20 through 89 years of age. The templates were done in five-year, 10-year, and multi-year intervals from 20 through 89 years, and consist of average T1W for the head and brain, and segmenting priors for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). It was found that age-appropriate templates provided less biased tissue classification estimates than age-inappropriate reference data and reference data based on young adult templates. This database is available for use by other investigators and clinicians for their MRI studies, as well as other types of neuroimaging and electrophysiological research.1 PMID:25904864

  5. Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

    PubMed

    Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2016-05-01

    We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. PMID:25870909

  6. Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.

    PubMed

    Lu, Jianghua; E, Lezi; Wang, Wenfang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Phil; Choi, In Young; Brooks, William M; Burns, Jeffrey M; Aires, Daniel; Swerdlow, Russell H

    2011-04-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. PMID:21244426

  7. Alternate Day Fasting Impacts the Brain Insulin Signaling Pathway of Young Adult Male C57BL/6 Mice

    PubMed Central

    Lu, Jianghua; Lezi, E; Wang, WenFang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Sang-Pil; Choi, In Young; Brooks, William M.; Burns, Jeffrey M.; Aires, Daniel; Swerdlow, Russell H.

    2011-01-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five month-old male mice were placed in ad libitum (AL) or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF+AO) fed group. During the 24 hour fast blood glucose levels initially fell but stabilized within 6 hours of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and GSK3β phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMPK phosphorylation, SIRT1 phosphorylation, PGC1a levels, and COX4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. PMID:21244426

  8. Transient postnatal fluoxetine leads to decreased brain arachidonic acid metabolism and cytochrome P450 4A in adult mice

    PubMed Central

    Ramadan, Epolia; Blanchard, Helene; Cheon, Yewon; Fox, Meredith A.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Basselin, Mireille

    2014-01-01

    Fetal and perinatal exposure to selective serotonin (5-HT) reuptake inhibitors (SSRIs) has been reported to alter childhood behavior, while transient early exposure in rodents is reported to alter their behavior and decrease brain extracellular 5-HT in adulthood. Since 5-HT2A/2C receptor-mediated neurotransmission can involve G-protein coupled activation of cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (ARA) from synaptic membrane phospholipid, we hypothesized that transient postnatal exposure to fluoxetine would decrease brain ARA metabolism in adult mice. Brain ARA incorporation coefficients k* and rates Jin were quantitatively imaged following intravenous [1-14C]ARA infusion of unanesthetized adult mice that had been injected daily with fluoxetine (10 mg/kg i.p.) or saline during postnatal days P4–P21. Expression of brain ARA metabolic enzymes and other relevant markers also was measured. On neuroimaging, k* and Jin was decreased widely in early fluoxetine- compared to saline-treated adult mice. Of the enzymes measured, cPLA2 activity was unchanged, while Ca2+-independent iPLA2 activity was increased. There was a significant 74% reduced protein level of cytochrome P450 (CYP) 4A, which can convert ARA to 20-HETE. Reduced brain ARA metabolism in adult mice transiently exposed to postnatal fluoxetine, and a 74% reduction in CYP4A protein, suggest long-term effects independent of drug presence in brain ARA metabolism, and in CYP4A metabolites. Comparable changes in humans might contribute to reported altered behavior following early SSRI. PMID:24529827

  9. Long-term tracing of the BrdU label-retaining cells in adult rat brain.

    PubMed

    Zhang, Lei; Li, Haihong; Zeng, Shaopeng; Chen, Lu; Fang, Zeman; Huang, Qingjun

    2015-03-30

    Stem cells have been shown to be label-retaining, slow-cycling cells. In the adult mammalian central nervous system, the distribution of the stem cells is inconsistent among previous studies. The purpose of the present study was to determine the distribution of BrdU-LRCs and the cell types of the BrdU-LRCs in rat brain. To label BrdU-LRCs in rat brain, six newborn rats were administered intraperitoneal injections of BrdU 50mg/kg/time twice a day at 2h intervals, over four consecutive days. The BrdU-LRCs were detected by immunohistochemistry, the cell types were examined by double immunofluorescence staining for BrdU/GFAP and BrdU/MAP2, and the percentage of BrdU-LRCs was calculated following a chase period of 24 weeks post-injection. We observed that BrdU-LRCs distributed extensively in rat brain. In the LV, DG, striatum, cerebellum and neocortex, the percentage of BrdU-LRCs was 11.3 ± 2.5%, 10.9 ± 1.3%, 6.4 ± 1.2%, 5.6 ± 0.8%, and 4.9 ± 0.6%, respectively. The highest density of BrdU-LRCs was in LV and DG, the known stem cell sites in adult mammalian brain. Both BrdU/GFAP and BrdU/MAP2 double-staining cells could be detected in the above five brain subregions. Ongoing cell production was widespread in the adult mammalian brain, which would allow us to reevaluate the capacity and potentiality of the brain in homeostasis, wound repair, and regeneration. PMID:25681624

  10. Adult human dental pulp stem cells promote blood-brain barrier permeability through vascular endothelial growth factor-a expression.

    PubMed

    Winderlich, Joshua N; Kremer, Karlea L; Koblar, Simon A

    2016-06-01

    Stem cell therapy is a promising new treatment option for stroke. Intravascular administration of stem cells is a valid approach as stem cells have been shown to transmigrate the blood-brain barrier. The mechanism that causes this effect has not yet been elucidated. We hypothesized that stem cells would mediate localized discontinuities in the blood-brain barrier, which would allow passage into the brain parenchyma. Here, we demonstrate that adult human dental pulp stem cells express a soluble factor that increases permeability across an in vitro model of the blood-brain barrier. This effect was shown to be the result of vascular endothelial growth factor-a. The effect could be amplified by exposing dental pulp stem cell to stromal-derived factor 1, which stimulates vascular endothelial growth factor-a expression. These findings support the use of dental pulp stem cell in therapy for stroke. PMID:26661186

  11. New neurons in the adult brain: The role of sleep and consequences of sleep loss

    PubMed Central

    Meerlo, Peter; Mistlberger, Ralph E.; Jacobs, Barry L.; Heller, H. Craig; McGinty, Dennis

    2009-01-01

    Research over the last few decades has firmly established that new neurons are generated in selected areas of the adult mammalian brain, particularly the dentate gyrus of the hippocampal formation and the subventricular zone of the lateral ventricles. The function of adult-born neurons is still a matter of debate. In the case of the hippocampus, integration of new cells in to the existing neuronal circuitry may be involved in memory processes and the regulation of emotionality. In recent years, various studies have examined how the production of new cells and their development into neurons is affected by sleep and sleep loss. While disruption of sleep for a period shorter than one day appears to have little effect on the basal rate of cell proliferation, prolonged restriction or disruption of sleep may have cumulative effects leading to a major decrease in hippocampal cell proliferation, cell survival and neurogenesis. Importantly, while short sleep deprivation may not affect the basal rate of cell proliferation, one study in rats shows that even mild sleep restriction may interfere with the increase in neurogenesis that normally occurs with hippocampus-dependent learning. Since sleep deprivation also disturbs memory formation, these data suggest that promoting survival, maturation and integration of new cells may be an unexplored mechanism by which sleep supports learning and memory processes. Most methods of sleep deprivation that have been employed affect both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Available data favor the hypothesis that decreases in cell proliferation are related to a reduction in REM sleep, whereas decreases in the number of cells that subsequently develop into adult neurons may be related to reductions in both NREM and REM sleep. The mechanisms by which sleep loss affects different aspects of adult neurogenesis are unknown. It has been proposed that adverse effects of sleep disruption may be mediated by stress and

  12. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    PubMed Central

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  13. Analysis of adult neurogenesis: evidence for a prominent "non-neurogenic" DCX-protein pool in rodent brain.

    PubMed

    Kremer, Thomas; Jagasia, Ravi; Herrmann, Annika; Matile, Hugues; Borroni, Edilio; Francis, Fiona; Kuhn, Hans Georg; Czech, Christian

    2013-01-01

    Here, we have developed a highly sensitive immunoassay for Dcx to characterize expression in brain and cerebrospinal fluid (CSF) of rodents. We demonstrate that Dcx is widely expressed during development in various brain regions and as well can be detected in cerebrospinal fluid of rats (up to 30 days postnatal). While Dcx protein level decline in adulthood and were detectable in neurogenic regions of the adult rodent brain, similar levels were also detectable in brain regions expected to bear no neurogenesis including the cerebral cortex and CA1/CA3 enriched hippocampus. We monitored DCX protein levels after paradigms to increase or severely decrease adult hippocampal neurogenesis, namely physical activity and cranial radiation, respectively. In both paradigms, Dcx protein- and mRNA-levels clearly reflected changes in neurogenesis in the hippocampus. However, basal Dcx-levels are unaffected in non-neurogenic regions (e.g. CA1/CA3 enriched hippocampus, cortex). These data suggest that there is a substantial "non-neurogenic" pool of Dcx- protein, whose regulation can be uncoupled from adult neurogenesis suggesting caution for the interpretation of such studies. PMID:23690918

  14. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain.

    PubMed

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  15. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    NASA Technical Reports Server (NTRS)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  16. Analysis of Adult Neurogenesis: Evidence for a Prominent “Non-Neurogenic” DCX-Protein Pool in Rodent Brain

    PubMed Central

    Kremer, Thomas; Jagasia, Ravi; Herrmann, Annika; Matile, Hugues; Borroni, Edilio; Francis, Fiona; Kuhn, Hans Georg; Czech, Christian

    2013-01-01

    Here, we have developed a highly sensitive immunoassay for Dcx to characterize expression in brain and cerebrospinal fluid (CSF) of rodents. We demonstrate that Dcx is widely expressed during development in various brain regions and as well can be detected in cerebrospinal fluid of rats (up to 30 days postnatal). While Dcx protein level decline in adulthood and were detectable in neurogenic regions of the adult rodent brain, similar levels were also detectable in brain regions expected to bear no neurogenesis including the cerebral cortex and CA1/CA3 enriched hippocampus. We monitored DCX protein levels after paradigms to increase or severely decrease adult hippocampal neurogenesis, namely physical activity and cranial radiation, respectively. In both paradigms, Dcx protein- and mRNA-levels clearly reflected changes in neurogenesis in the hippocampus. However, basal Dcx-levels are unaffected in non-neurogenic regions (e.g. CA1/CA3 enriched hippocampus, cortex). These data suggest that there is a substantial “non-neurogenic” pool of Dcx- protein, whose regulation can be uncoupled from adult neurogenesis suggesting caution for the interpretation of such studies. PMID:23690918

  17. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    PubMed

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  18. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    PubMed Central

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-01-01

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  19. Variation in social relationships relates to song preferences and EGR1 expression in a female songbird.

    PubMed

    Schubloom, Hannah E; Woolley, Sarah C

    2016-09-01

    Social experiences can profoundly shape social behavior and the underlying neural circuits. Across species, the formation of enduring social relationships is associated with both neural and behavioral changes. However, it remains unclear how longer-term relationships between individuals influence brain and behavior. Here, we investigated how variation in social relationships relates to variation in female preferences for and neural responses to song in a pair-bonding songbird. We assessed variation in the interactions between individuals in male-female zebra finch pairs and found that female preferences for their mate's song were correlated with the degree of affiliation and amount of socially modulated singing, but not with the frequency of aggressive interactions. Moreover, variation in measures of pair quality and preference correlated with variation in the song-induced expression of EGR1, an immediate early gene related to neural activity and plasticity, in brain regions important for auditory processing and social behavior. For example, females with weaker preferences for their mate's song had greater EGR1 expression in the nucleus Taeniae, the avian homologue of the mammalian medial amygdala, in response to playback of their mate's courtship song. Our data indicate that the quality of social interactions within pairs relates to variation in song preferences and neural responses to ethologically relevant stimuli and lend insight into neural circuits sensitive to social information. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1029-1040, 2016. PMID:26713856

  20. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2016-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. PMID:26609811

  1. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain

    PubMed Central

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. DOI: http://dx.doi.org/10.7554/eLife.11290.001 PMID:26609811

  2. Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry.

    PubMed

    Hill, Joanna M; Hauser, Janet M; Sheppard, Lia M; Abebe, Daniel; Spivak-Pohis, Irit; Kushnir, Michal; Deitch, Iris; Gozes, Illana

    2007-01-01

    Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding. These data suggest that blockage of VIP during the development of the nervous system can result in permanent changes to the brain. In the current study, pregnant mice were treated with a VIP antagonist during embryonic days 8 through 10. The adult male offspring were examined in tests of novelty, paired activity, and social recognition. Brain tissue was examined for several measures of chemistry and gene expression of VIP and related compounds. Glial cells from the cortex of treated newborn mice were plated with neurons and examined for VIP binding and their ability to enhance neuronal survival. Treated adult male mice exhibited increased anxiety-like behavior and deficits in social behavior. Brain tissue exhibited regionally specific changes in VIP chemistry and a trend toward increased gene expression of VIP and related compounds that reached statistical significance in the VIP receptor, VPAC-1, in the female cortex. When compared to control astrocytes, astrocytes from treated cerebral cortex produced further increases in neuronal survival with excess synaptic connections and reduced VIP binding. In conclusion, impaired VIP activity during mouse embryogenesis resulted in permanent changes to both adult brain chemistry/cell biology and behavior with aspects of autism-like social deficits. PMID:17726225

  3. In vivo imaging of endogenous neural stem cells in the adult brain

    PubMed Central

    Rueger, Maria Adele; Schroeter, Michael

    2015-01-01

    The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3’-deoxy-3’-[18F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting. PMID:25621107

  4. In vivo imaging of endogenous neural stem cells in the adult brain.

    PubMed

    Rueger, Maria Adele; Schroeter, Michael

    2015-01-26

    The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'-[(18)F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting. PMID:25621107

  5. Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

    PubMed

    Chai, Xiaoqian J; Berken, Jonathan A; Barbeau, Elise B; Soles, Jennika; Callahan, Megan; Chen, Jen-Kai; Klein, Denise

    2016-01-20

    There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human

  6. Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults

    PubMed Central

    Wong, Chelsea N.; Chaddock-Heyman, Laura; Voss, Michelle W.; Burzynska, Agnieszka Z.; Basak, Chandramallika; Erickson, Kirk I.; Prakash, Ruchika S.; Szabo-Reed, Amanda N.; Phillips, Siobhan M.; Wojcicki, Thomas; Mailey, Emily L.; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59–80 years). Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA), thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function. PMID:26321949

  7. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

    PubMed Central

    Forsyth, Jennifer K.; Bachman, Peter; Mathalon, Daniel H.; Roach, Brian J.; Asarnow, Robert F.

    2015-01-01

    Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers. PMID:26621715

  8. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain.

    PubMed

    Forsyth, Jennifer K; Bachman, Peter; Mathalon, Daniel H; Roach, Brian J; Asarnow, Robert F

    2015-12-15

    Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers. PMID:26621715

  9. The turnover of myelin phospholipids in the adult and developing rat brain

    PubMed Central

    Jungalwala, F. B.; Dawson, R. M. C.

    1971-01-01

    1. Inorganic [32P]phosphate, [U-14C]glycerol and [2-14C]ethanolamine were injected into the lateral ventricles in the brains of adult rats, and the labelling of individual phospholipids was followed over 2–4 months in both a microsomal and a highly purified myelin fraction. 2. All the phospholipids in myelin became appreciably labelled, although initially the specific radioactivities of the microsomal phospholipids were somewhat higher. Eventually the specific radioactivities in microsomal and myelin phospholipids fell rapidly at a rate corresponding to the decline of radioactivity in the acid-soluble pools. 3. Equivalent experiments carried out in developing rats with [32P]phosphate administered at the start of myelination showed some persistence of phospholipid labelling in the myelin, but this could partly be attributed to the greater retention of 32P in the acid-soluble phosphorus pool and recycling. 4. It is concluded that a substantial part of the phospholipid molecules in adult myelin membranes is readily exchangeable, although a small pool of slowly exchangeable material also exists. 5. A slow incorporation into or loss of labelled precursor from myelin phospholipids does not necessarily give a good indication of the rate of renewal of the molecules in the membrane. As presumably such labelled molecules originate by exchange with those in another membrane site (not necessarily where synthesis occurs) it is only possible to calculate the turnover rate in the myelin membrane if the behaviour of the specific radioactivity with time of the phospholipid molecules in the immediate precursor pool is known. PMID:5124379

  10. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  11. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain

    PubMed Central

    Guo, Junjie U.; Su, Yijing; Shin, Joo Heon; Shin, Jaehoon; Li, Hongda; Xie, Bin; Zhong, Chun; Hu, Shaohui; Le, Thuc; Fan, Guoping; Zhu, Heng; Chang, Qiang; Gao, Yuan; Ming, Guo-li; Song, Hongjun

    2014-01-01

    DNA methylation plays critical roles in the nervous system and has been traditionally considered to be restricted to CpG dinucleotides in metazoan genomes. Here we show that the single-base resolution DNA methylome from adult mouse dentate neurons consists of both CpG (~75%) and CpH (~25%) methylation (H = A/C/T). Neuronal CpH methylation is conserved in human brains, enriched in low CpG-density regions, depleted at protein-DNA interaction sites, and anti-correlated with gene expression. Functionally, both mCpGs and mCpHs can repress transcription in vitro and are recognized by MeCP2 in neurons in vivo. Unlike most CpG methylation, CpH methylation is established de novo during neuronal maturation and requires DNMT3A for active maintenance in post-mitotic neurons. These characteristics of CpH methylation suggest a significantly expanded proportion of the neuronal genome under cytosine methylation regulation and provide a new foundation for understanding the role of this key epigenetic modification in the nervous system. PMID:24362762

  12. Daily marijuana use is not associated with brain morphometric measures in adolescents or adults.

    PubMed

    Weiland, Barbara J; Thayer, Rachel E; Depue, Brendan E; Sabbineni, Amithrupa; Bryan, Angela D; Hutchison, Kent E

    2015-01-28

    Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures. PMID:25632127

  13. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury.

    PubMed

    Kreber, Lisa A; Griesbach, Grace S; Ashley, Mark J

    2016-09-01

    This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

  14. Expression of gangliosides on glial and neuronal cells in normal and pathological adult human brain.

    PubMed

    Marconi, Silvia; De Toni, Luca; Lovato, Laura; Tedeschi, Elisa; Gaetti, Luigi; Acler, Michele; Bonetti, Bruno

    2005-12-30

    Few studies have assessed the glycolipid phenotype of glial cells in the human central nervous system (CNS) in situ. We investigated by immunohistochemistry the expression and cellular distribution of a panel of gangliosides (GM1, GM2, acetyl-GM3, GD1a, GD1b, GD2, GD3, GT1b, GQ1b and the A2B5 antibody) in adult, human normal and pathological brain, namely multiple sclerosis (MS) and other neurological diseases (OND). In normal conditions, we found diffuse expression in the white matter of most gangliosides tested, with the exception of acetyl-GM3, GT1b and GQ1b. By double immunofluorescence with phenotypic markers, GM1 and GD1b were preferentially expressed on GFAP+ astrocytes, GD1a on NG2+ oligodendrocyte precursors, A2B5 immunostained both populations, while GD2 was selectively present on mature oligodendrocytes. In the gray matter, only GM1, GD2 and A2B5 were present on neuronal cells. Interestingly, those gangliosides present on astrocytes in normal conditions were preferentially expressed on NG2+ cells in chronic MS lesions and in OND. Selective expression of GT1b upon astrocytes and NG2+ cells was instead observed in MS lesions, but not in OND. The definition of the glycolipid phenotype of CNS glial cells may be useful to identify distinct biological glial subsets and provide insights on the potential autoantigenic role of gangliosides in CNS autoimmune diseases. PMID:16313974

  15. Daily Marijuana Use Is Not Associated with Brain Morphometric Measures in Adolescents or Adults

    PubMed Central

    Thayer, Rachel E.; Depue, Brendan E.; Sabbineni, Amithrupa; Bryan, Angela D.; Hutchison, Kent E.

    2015-01-01

    Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures. PMID:25632127

  16. Adverse Outcomes Among Homeless Adolescents and Young Adults Who Report a History of Traumatic Brain Injury

    PubMed Central

    Harpin, Scott B.; Grubenhoff, Joseph A.; Rivara, Frederick P.

    2014-01-01

    Objectives. We examined the prevalence of self-reported traumatic brain injury (TBI) among homeless young people and explored whether sociodemographic characteristics, mental health diagnoses, substance use, exposure to violence, or difficulties with activities of daily living (ADLs) were associated with TBI. Methods. We analyzed data from the Wilder Homelessness Study, in which participants were recruited in 2006 and 2009 from streets, shelters, and locations in Minnesota that provide services to homeless individuals. Participants completed 30-minute interviews to collect information about history of TBI, homelessness, health status, exposure to violence (e.g., childhood abuse, assault), and other aspects of functioning. Results. Of the 2732 participating adolescents and young adults, 43% reported a history of TBI. Participants with TBI became homeless at a younger age and were more likely to report mental health diagnoses, substance use, suicidality, victimization, and difficulties with ADLs. The majority of participants (51%) reported sustaining their first injury prior to becoming homeless or at the same age of their first homeless episode (10%). Conclusions. TBI occurs frequently among homeless young people and is a marker of adverse outcomes such as mental health difficulties, suicidal behavior, substance use, and victimization. PMID:25122029

  17. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury

    PubMed Central

    Griesbach, Grace S.; Ashley, Mark J.

    2016-01-01

    Abstract This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

  18. Fat brains, greedy genes, and parent power: a biobehavioural risk model of child and adult obesity.

    PubMed

    Carnell, Susan; Kim, Yale; Pryor, Katherine

    2012-06-01

    We live in a world replete with opportunities to overeat highly calorific, palatable foods - yet not everyone becomes obese. Why? We propose that individuals show differences in appetitive traits (e.g. food cue responsiveness, satiety sensitivity) that manifest early in life and predict their eating behaviours and weight trajectories. What determines these traits? Parental feeding restriction is associated with higher child adiposity, pressure to eat with lower adiposity, and both strategies with less healthy eating behaviours, while authoritative feeding styles coincide with more positive outcomes. But, on the whole, twin and family studies argue that nature has a greater influence than nurture on adiposity and eating behaviour, and behavioural investigations of genetic variants that are robustly associated with obesity (e.g. FTO) confirm that genes influence appetite. Meanwhile, a growing body of neuroimaging studies in adults, children and high risk populations suggests that structural and functional variation in brain networks associated with reward, emotion and control might also predict appetite and obesity, and show genetic influence. Together these different strands of evidence support a biobehavioural risk model of obesity development. Parental feeding recommendations should therefore acknowledge the powerful - but modifiable - contribution of genetic and neurological influences to children's eating behaviour. PMID:22724640

  19. Programming Hippocampal Neural Stem/Progenitor Cells into Oligodendrocytes Enhances Remyelination in the Adult Brain after Injury.

    PubMed

    Braun, Simon M G; Pilz, Gregor-Alexander; Machado, Raquel A C; Moss, Jonathan; Becher, Burkhard; Toni, Nicolas; Jessberger, Sebastian

    2015-06-23

    Demyelinating diseases are characterized by a loss of oligodendrocytes leading to axonal degeneration and impaired brain function. Current strategies used for the treatment of demyelinating disease such as multiple sclerosis largely rely on modulation of the immune system. Only limited treatment options are available for treating the later stages of the disease, and these treatments require regenerative therapies to ameliorate the consequences of oligodendrocyte loss and axonal impairment. Directed differentiation of adult hippocampal neural stem/progenitor cells (NSPCs) into oligodendrocytes may represent an endogenous source of glial cells for cell-replacement strategies aiming to treat demyelinating disease. Here, we show that Ascl1-mediated conversion of hippocampal NSPCs into mature oligodendrocytes enhances remyelination in a diphtheria-toxin (DT)-inducible, genetic model for demyelination. These findings highlight the potential of targeting hippocampal NSPCs for the treatment of demyelinated lesions in the adult brain. PMID:26074082

  20. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function.

    PubMed

    Garza-Lombó, Carla; Gonsebatt, María E

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  1. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

    PubMed Central

    Garza-Lombó, Carla; Gonsebatt, María E.

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  2. The Mediating Role of Visuospatial Planning Skills on Adaptive Function Among Young-Adult Survivors of Childhood Brain Tumor.

    PubMed

    King, Tricia Z; Smith, Kristen M; Ivanisevic, Mirjana

    2015-08-01

    The Boston Qualitative Scoring System (BQSS) was used as a method to examine executive skills on the Rey-Osterrieth complex figure (ROCF). Young-adult survivors of childhood brain tumor (N = 31) and a demographically-matched comparison group (N = 33) completed the ROCF copy version and Grooved Pegboard, and informants were administered the Scales of Independent Behavior-Revised (SIB-R) and Behavior Rating Inventory of Executive Function (BRIEF). Survivors had significantly lower BQSS planning and SIB-R community living skills and greater perseveration. Mediation analyses found that BQSS planning skills mediate the relationship between group and community living skills. Convergent findings of the BRIEF Planning, and discriminant findings with the BQSS Fragmentation, BRIEF Emotional Control, and Grooved Pegboard support the planning construct as the specific mediator in this model. Together, these findings highlight the role of planning skills in adaptive functions of young-adult survivors of childhood brain tumor. PMID:26055499

  3. Environmental changes in oxygen tension reveal ROS-dependent neurogenesis and regeneration in the adult newt brain.

    PubMed

    Hameed, L Shahul; Berg, Daniel A; Belnoue, Laure; Jensen, Lasse D; Cao, Yihai; Simon, András

    2015-01-01

    Organisms need to adapt to the ecological constraints in their habitat. How specific processes reflect such adaptations are difficult to model experimentally. We tested whether environmental shifts in oxygen tension lead to events in the adult newt brain that share features with processes occurring during neuronal regeneration under normoxia. By experimental simulation of varying oxygen concentrations, we show that hypoxia followed by re-oxygenation lead to neuronal death and hallmarks of an injury response, including activation of neural stem cells ultimately leading to neurogenesis. Neural stem cells accumulate reactive oxygen species (ROS) during re-oxygenation and inhibition of ROS biosynthesis counteracts their proliferation as well as neurogenesis. Importantly, regeneration of dopamine neurons under normoxia also depends on ROS-production. These data demonstrate a role for ROS-production in neurogenesis in newts and suggest that this role may have been recruited to the capacity to replace lost neurons in the brain of an adult vertebrate. PMID:26485032

  4. Enhanced Adult Neurogenesis Increases Brain Stiffness: In Vivo Magnetic Resonance Elastography in a Mouse Model of Dopamine Depletion

    PubMed Central

    Klein, Charlotte; Hain, Elisabeth G.; Braun, Juergen; Riek, Kerstin; Mueller, Susanne

    2014-01-01

    The mechanical network of the brain is a major contributor to neural health and has been recognized by in vivo magnetic resonance elastography (MRE) to be highly responsive to diseases. However, until now only brain softening was observed and no mechanism was known that reverses the common decrement of neural elasticity during aging or disease. We used MRE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model for dopaminergic neurodegeneration as observed in Parkinson’s disease (PD) to study the mechanical response of the brain on adult hippocampal neurogenesis as a robust correlate of neuronal plasticity in healthy and injured brain. We observed a steep transient rise in elasticity within the hippocampal region of up to over 50% six days after MPTP treatment correlating with increased neuronal density in the dentate gyrus, which could not be detected in healthy controls. Our results provide the first indication that new neurons reactively generated following neurodegeneration substantially contribute to the mechanical scaffold of the brain. Diagnostic neuroimaging may thus target on regions of the brain displaying symptomatically elevated elasticity values for the detection of neuronal plasticity following neurodegeneration. PMID:24667730

  5. Brain-specific tropomyosins TMBr-1 and TMBr-3 have distinct patterns of expression during development and in adult brain.

    PubMed Central

    Stamm, S; Casper, D; Lees-Miller, J P; Helfman, D M

    1993-01-01

    In this study we report on the developmental and regional expression of two brain-specific isoforms of tropomyosin, TMBr-1 and TMBr-3, that are generated from the rat alpha-tropomyosin gene via the use of alternative promoters and alternative RNA splicing. Western blot analysis using an exon-specific peptide polyclonal antibody revealed that the two isoforms are differentially expressed in development with TMBr-3 appearing in the embryonic brain at 16 days of gestation, followed by the expression of TMBr-1 at 20 days after birth. TMBr-3 was detected in all brain regions examined, whereas TMBr-1 was detected predominantly in brain areas that derived from the prosencephalon. Immunocytochemical studies on mixed primary cultures made from rat embryonic midbrain indicate that expression of the brain-specific epitope is restricted to neurons. The developmental pattern and neuronal localization of these forms of tropomyosin suggest that these isoforms have a specialized role in the development and plasticity of the nervous system. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7694294

  6. Whole-brain grey matter density predicts balance stability irrespective of age and protects older adults from falling.

    PubMed

    Boisgontier, Matthieu P; Cheval, Boris; van Ruitenbeek, Peter; Levin, Oron; Renaud, Olivier; Chanal, Julien; Swinnen, Stephan P

    2016-03-01

    Functional and structural imaging studies have demonstrated the involvement of the brain in balance control. Nevertheless, how decisive grey matter density and white matter microstructural organisation are in predicting balance stability, and especially when linked to the effects of ageing, remains unclear. Standing balance was tested on a platform moving at different frequencies and amplitudes in 30 young and 30 older adults, with eyes open and with eyes closed. Centre of pressure variance was used as an indicator of balance instability. The mean density of grey matter and mean white matter microstructural organisation were measured using voxel-based morphometry and diffusion tensor imaging, respectively. Mixed-effects models were built to analyse the extent to which age, grey matter density, and white matter microstructural organisation predicted balance instability. Results showed that both grey matter density and age independently predicted balance instability. These predictions were reinforced when the level of difficulty of the conditions increased. Furthermore, grey matter predicted balance instability beyond age and at least as consistently as age across conditions. In other words, for balance stability, the level of whole-brain grey matter density is at least as decisive as being young or old. Finally, brain grey matter appeared to be protective against falls in older adults as age increased the probability of losing balance in older adults with low, but not moderate or high grey matter density. No such results were observed for white matter microstructural organisation, thereby reinforcing the specificity of our grey matter findings. PMID:26979897

  7. Low Current-driven Micro-electroporation Allows Efficient In Vivo Delivery of Nonviral DNA into the Adult Mouse Brain

    PubMed Central

    Vry, Jochen De; Martínez-Martínez, Pilar; Losen, Mario; Bode, Gerard H; Temel, Yasin; Steckler, Thomas; Steinbusch, Harry WM; Baets, Marc De; Prickaerts, Jos

    2010-01-01

    Viral gene transfer or transgenic animals are commonly used technologies to alter gene expression in the adult brain, although these approaches lack spatial specificity and are time consuming. We delivered plasmid DNA locally into the brain of adult C57BL/6 mice in vivo by voltage- and current-controlled electroporation. The low current-controlled delivery of unipolar square wave pulses of 125 µA with microstimulation electrodes at the injection site gave 16 times higher transfection rates than a voltage-controlled electroporation protocol with plate electrodes resulting in currents of about 400 mA. Transfection was restricted to the target region and no damage due to the electric pulses was found. Our current-controlled electroporation protocol indicated that the use of very low currents resulting in applied voltages within the physiological range of the membrane potential, allows efficient transfection of nonviral plasmid DNA. In conclusion, low current-controlled electroporation is an excellent approach for electroporation in the adult brain, i.e., gene function can be influenced locally at a high level with no mortality and minimal tissue damage. PMID:20389292

  8. Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

    PubMed Central

    Langbecker, Danette; Janda, Monika

    2014-01-01

    Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

  9. Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model

    PubMed Central

    Acosta, Sandra A.; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Grimmig, Bethany; Diamond, David; Sanberg, Paul R.; Bickford, Paula C.; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes. PMID:23301065

  10. A preliminary study of sex differences in brain activation during a spatial navigation task in healthy adults.

    PubMed

    Sneider, Jennifer Tropp; Sava, Simona; Rogowska, Jadwiga; Yurgelun-Todd, Deborah A

    2011-10-01

    The hippocampus plays a significant role in spatial memory processing, with sex differences being prominent on various spatial tasks. This study examined sex differences in healthy adults, using functional magnetic resonance imaging (fMRI) in areas implicated in spatial processing during navigation of a virtual analogue of the Morris water-maze. There were three conditions: learning, hidden, and visible control. There were no significant differences in performance measures. However, sex differences were found in regional brain activation during learning in the right hippocampus, right parahippocampal gyrus, and the cingulate cortex. During the hidden condition, the hippocampus, parahippocampal gyrus, and cingulate cortex were activated in both men and women. Additional brain areas involved in spatial processing may be recruited in women when learning information about the environment, by utilizing external cues (landmarks) more than do men, contributing to the observed sex differences in brain activation. PMID:22185061

  11. A Novel Procedure for Rapid Imaging of Adult Mouse Brains with MicroCT Using Iodine-Based Contrast

    PubMed Central

    Anderson, Ryan; Maga, A. Murat

    2015-01-01

    High-resolution Magnetic Resonance Imaging (MRI) has been the primary modality for obtaining 3D cross-sectional anatomical information in animals for soft tissue, particularly brain. However, costs associated with MRI can be considerably high for large phenotypic screens for gross differences in the structure of the brain due to pathology and/or experimental manipulations. MicroCT (mCT), especially benchtop mCT, is becoming a common laboratory equipment with throughput rates equal or faster than any form of high-resolution MRI at lower costs. Here we explore adapting previously developed contrast based mCT to image adult mouse brains in-situ. We show that 2% weight per volume (w/v) iodine-potassium iodide solution can be successfully used to image adult mouse brains within 48 hours post-mortem when a structural support matrix is used. We demonstrate that hydrogel can be effectively used as a perfusant which limits the tissue shrinkage due to iodine. PMID:26571123

  12. A conceptual framework for clutch size evolution in songbirds

    USGS Publications Warehouse

    Martin, Thomas E.

    2014-01-01

    Causes of evolved differences in clutch size among songbird species remain debated. I propose a new conceptual framework that integrates aspects of traditional life history theory, while including novel elements, to explain evolution of clutch size among songbirds. I review evidence that selection by nest predation on length of time that offspring develop in the nest creates a gradient in offspring characteristics at nest-leaving (fledging), including flight mobility, spatial dispersion, and self-feeding rate. I postulate that this gradient has consequences for offspring mortality rates and parental energy expenditure per offspring. These consequences then determine how reproductive effort is partitioned among offspring, while reproductive effort evolves from age-specific mortality effects. Using data from a long-term site in Arizona, as well as from the literature, I provide support for hypothesized relationships. Nestling development period consistently explains fledgling mortality, energy expenditure per offspring, and clutch size while accounting for reproductive effort (i.e., total energy expenditure) to thereby support the framework. Tests in this paper are not definitive, but they document previously unrecognized relationships and address diverse traits (developmental strategies, parental care strategies, energy requirements per offspring, evolution of reproductive effort, clutch size) that justify further investigations of hypotheses proposed here.

  13. A Mechanism for Frequency Modulation in Songbirds Shared with Humans

    PubMed Central

    Margoliash, Daniel

    2013-01-01

    In most animals that vocalize, control of fundamental frequency is a key element for effective communication. In humans, subglottal pressure controls vocal intensity but also influences fundamental frequency during phonation. Given the underlying similarities in the biomechanical mechanisms of vocalization in humans and songbirds, songbirds offer an attractive opportunity to study frequency modulation by pressure. Here, we present a novel technique for dynamic control of subsyringeal pressure in zebra finches. By regulating the opening of a custom-built fast valve connected to the air sac system, we achieved partial or total silencing of specific syllables, and could modify syllabic acoustics through more complex manipulations of air sac pressure. We also observed that more nuanced pressure variations over a limited interval during production of a syllable concomitantly affected the frequency of that syllable segment. These results can be explained in terms of a mathematical model for phonation that incorporates a nonlinear description for the vocal source capable of generating the observed frequency modulations induced by pressure variations. We conclude that the observed interaction between pressure and frequency was a feature of the source, not a result of feedback control. Our results indicate that, beyond regulating phonation or its absence, regulation of pressure is important for control of fundamental frequencies of vocalizations. Thus, although there are separate brainstem pathways for syringeal and respiratory control of song production, both can affect airflow and frequency. We hypothesize that the control of pressure and frequency is combined holistically at higher levels of the vocalization pathways. PMID:23825417

  14. Biomechanics and control of vocalization in a non-songbird.

    PubMed

    Elemans, Coen P H; Zaccarelli, Riccardo; Herzel, Hanspeter

    2008-07-01

    The neuromuscular control of vocalization in birds requires complicated and precisely coordinated motor control of the vocal organ (i.e. the syrinx), the respiratory system and upper vocal tract. The biomechanics of the syrinx is very complex and not well understood. In this paper, we aim to unravel the contribution of different control parameters in the coo of the ring dove (Streptopelia risoria) at the syrinx level. We designed and implemented a quantitative biomechanical syrinx model that is driven by physiological control parameters and includes a muscle model. Our simple nonlinear model reproduces the coo, including the inspiratory note, with remarkable accuracy and suggests that harmonic content of song can be controlled by the geometry and rest position of the syrinx. Furthermore, by systematically switching off the control parameters, we demonstrate how they affect amplitude and frequency modulations and generate new experimentally testable hypotheses. Our model suggests that independent control of amplitude and frequency seems not to be possible with the simple syringeal morphology of the ring dove. We speculate that songbirds evolved a syrinx design that uncouples the control of different sound parameters and allows for independent control. This evolutionary key innovation provides an additional explanation for the rapid diversification and speciation of the songbirds. PMID:17999946

  15. Migration and the evolution of duetting in songbirds

    PubMed Central

    Logue, David M.; Hall, Michelle L.

    2014-01-01

    Many groups of animals defend shared resources with coordinated signals. The best-studied of these signals are the vocal duets produced by mated pairs of birds. Duets are believed to be more common among tropical-breeding species, but a comprehensive test of this hypothesis is lacking, and the mechanisms that generate latitudinal patterns in duetting are not known. We used a stratified sample of 372 songbird species to conduct the first broad-scale, phylogenetically explicit analysis of duet evolution. We found that duetting evolves in association with the absence of migration, but not with sexual monochromatism or tropical breeding. We conclude that the evolution of migration exerts a major influence on the evolution of duetting. The perceived association between tropical breeding and duetting may be a by-product of the migration–duetting relationship. Migration reduces the average duration of partnerships, potentially reducing the benefits of cooperative behaviour, including duetting. Ultimately, the evolution of coordinated resource-defence signals in songbirds may be driven by ecological conditions that favour sedentary lifestyles and social stability. PMID:24619447

  16. Agricultural management affects evolutionary processes in a migratory songbird

    USGS Publications Warehouse

    Perlut, N.G.; Freeman-Gallant, C. R.; Strong, A.M.; Donovan, T.M.; Kilpatrick, C.W.; Zalik, N.J.

    2008-01-01

    Hay harvests have detrimental ecological effects on breeding songbirds, as harvesting results in nest failure. Importantly, whether harvesting also affects evolutionary processes is not known. We explored how hay harvest affected social and genetic mating patterns, and thus, the overall opportunity for sexual selection and evolutionary processes for a ground-nesting songbird, the Savannah sparrow (Passerculus sandwichensis). On an unharvested field, 55% of females were in polygynous associations, and social polygyny was associated with greater rates of extra-pair paternity (EPP). In this treatment, synchrony explained variation in EPP rates, as broods by more synchronous females had more EPP than broods by asynchronous females. In contrast, on a harvested field, simultaneous nest failure caused by haying dramatically decreased the overall incidence of EPP by increasing the occurrence of social monogamy and, apparently, the ability of polygynous males to maintain paternity in their own nests. Despite increased social and genetic monogamy, these haying-mediated changes in mating systems resulted in greater than twofold increase in the opportunity for sexual selection. This effect arose, in part, from a 30% increase in the variance associated with within-pair fertilization success, relative to the unharvested field. This effect was caused by a notable increase (+110%) in variance associated with the quality of social mates following simultaneous nest failure. Because up to 40% of regional habitat is harvested by early June, these data may demonstrate a strong population-level effect on mating systems, sexual selection, and consequently, evolutionary processes. ?? 2008 The Authors.

  17. A conceptual framework for clutch-size evolution in songbirds.

    PubMed

    Martin, Thomas E

    2014-03-01

    Causes of evolved differences in clutch size among songbird species remain debated. I propose a new conceptual framework that integrates aspects of traditional life-history theory while including novel elements to explain evolution of clutch size among songbirds. I review evidence that selection by nest predation on length of time that offspring develop in the nest creates a gradient in offspring characteristics at nest leaving (fledging), including flight mobility, spatial dispersion, and self-feeding rate. I postulate that this gradient has consequences for offspring mortality rates and parental energy expenditure per offspring. These consequences then determine how reproductive effort is partitioned among offspring, while reproductive effort evolves from age-specific mortality effects. Using data from a long-term site in Arizona, as well as from the literature, I provide support for hypothesized relationships. Nestling development period consistently explains fledgling mortality, energy expenditure per offspring, and clutch size while accounting for reproductive effort (i.e., total energy expenditure) to thereby support the framework. Tests in this article are not definitive, but they document previously unrecognized relationships and address diverse traits (developmental strategies, parental care strategies, energy requirements per offspring, evolution of reproductive effort, clutch size) that justify further investigations of hypotheses proposed here. PMID:24561596

  18. Expression and Regulation of the Fkbp5 Gene in the Adult Mouse Brain

    PubMed Central

    Scharf, Sebastian H.; Liebl, Claudia; Binder, Elisabeth B.

    2011-01-01

    Background Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR). The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5). Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse. Methodology/Principal Findings In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN) and the central amygdala (CeA). Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA. Conclusions/Significance Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain. PMID:21347384

  19. Development and psychometric properties of an informant assessment scale of theory of mind for adults with traumatic brain injury.

    PubMed

    Zhang, Dengke; Pang, Yanxia; Cai, Weixiong; Fazio, Rachel L; Ge, Jianrong; Su, Qiaorong; Xu, Shuiqin; Pan, Yinan; Chen, Sanmei; Zhang, Hongwei

    2016-08-01

    Impairment of theory of mind (ToM) is a common phenomenon following traumatic brain injury (TBI) that has clear effects on patients' social functioning. A growing body of research has focused on this area, and several methods have been developed to assess ToM deficiency. Although an informant assessment scale would be useful for examining individuals with TBI, very few studies have adopted this approach. The purpose of the present study was to develop an informant assessment scale of ToM for adults with traumatic brain injury (IASToM-aTBI) and to test its reliability and validity with 196 adults with TBI and 80 normal adults. A 44-item scale was developed following a literature review, interviews with patient informants, consultations with experts, item analysis, and exploratory factor analysis (EFA). The following three common factors were extracted: social interaction, understanding of beliefs, and understanding of emotions. The psychometric analyses indicate that the scale has good internal consistency reliability, split-half reliability, test-retest reliability, inter-rater reliability, structural validity, discriminate validity and criterion validity. These results provide preliminary evidence that supports the reliability and validity of the IASToM-aTBI as a ToM assessment tool for adults with TBI. PMID:25849662

  20. Seasonal regulation of structural plasticity and neurogenesis in the adult mammalian brain: focus on the sheep hypothalamus.

    PubMed

    Migaud, Martine; Butrille, Lucile; Batailler, Martine

    2015-04-01

    To cope with variations in the environment, most mammalian species exhibit seasonal cycles in physiology and behaviour. Seasonal plasticity during the lifetime contributes to seasonal physiology. Over the years, our ideas regarding adult brain plasticity and, more specifically, hypothalamic plasticity have greatly evolved. Along with the two main neurogenic regions, namely the hippocampal subgranular and lateral ventricle subventricular zones, the hypothalamus, which is the central homeostatic regulator of numerous physiological functions that comprise sexual behaviours, feeding and metabolism, also hosts neurogenic niches. Both endogenous and exogenous factors, including the photoperiod, modulate the hypothalamic neurogenic capacities. The present review describes the effects of season on adult morphological plasticity and neurogenesis in seasonal species, for which the photoperiod is a master environmental cue for the successful programming of seasonal functions. In addition, the potential functional significance of adult neurogenesis in the mediation of the seasonal control of reproduction and feeding is discussed. PMID:25462590

  1. Traumatic brain injury and age at onset of cognitive impairment in older adults.

    PubMed

    Li, Wei; Risacher, Shannon L; McAllister, Thomas W; Saykin, Andrew J

    2016-07-01

    There is a deficiency of knowledge regarding how traumatic brain injury (TBI) is associated with age at onset (AAO) of cognitive impairment in older adults. Participants with a TBI history were identified from the Alzheimer's disease neuroimaging initiative (ADNI 1/GO/2) medical history database. Using an analysis of covariance (ANCOVA) model, the AAO was compared between those with and without TBI, and potential confounding factors were controlled. The AAO was also compared between those with mild TBI (mTBI) and moderate or severe TBI (sTBI). Lastly, the effects of mTBI were analyzed on the AAO of participants with clinical diagnoses of either mild cognitive impairment (MCI) or Alzheimer's disease (AD). The AAO for a TBI group was 68.2 ± 1.1 years [95 % confidence interval (CI) 66.2-70.3, n = 62], which was significantly earlier than the AAO for the non-TBI group of 70.9 ± 0.2 years (95 % CI 70.5-71.4, n = 1197) (p = 0.013). Participants with mTBI history showed an AAO of 68.5 ± 1.1 years (n = 56), which was significantly earlier than the AAO for the non-TBI group (p = 0.032). Participants with both MCI and mTBI showed an AAO of 66.5 ± 1.3 years (95 % CI 63.9-69.1, n = 45), compared to 70.6 ± 0.3 years for the non-TBI MCI group (95 % CI 70.1-71.1, n = 935) (p = 0.016). As a conclusion, a history of TBI may accelerate the AAO of cognitive impairment by two or more years. These results were consistent with reports of TBI as a significant risk factor for cognitive decline in older adults, and TBI is associated with an earlier AAO found in patients with MCI or AD. PMID:27007484

  2. PRENATAL ALCOHOL EXPOSURE ALTERS STEADY-STATE AND ACTIVATED GENE EXPRESSION IN THE ADULT RAT BRAIN

    PubMed Central

    Stepien, Katarzyna A.; Lussier, Alexandre A.; Neumann, Sarah M.; Pavlidis, Paul; Kobor, Michael S.; Weinberg, Joanne

    2016-01-01

    Background Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems . We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freund’s adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression

  3. Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

    PubMed Central

    Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

    2015-01-01

    Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087

  4. Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an 'interface' nucleus.

    PubMed

    Pawlisch, B A; Remage-Healey, L

    2015-01-22

    Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these

  5. Advanced BrainAGE in older adults with type 2 diabetes mellitus.

    PubMed

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The "Brain Age Gap Estimation" (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM

  6. Brain structures and functional connectivity associated with individual differences in Internet tendency in healthy young adults.

    PubMed

    Li, Weiwei; Li, Yadan; Yang, Wenjing; Zhang, Qinglin; Wei, Dongtao; Li, Wenfu; Hitchman, Glenn; Qiu, Jiang

    2015-04-01

    Internet addiction (IA) incurs significant social and financial costs in the form of physical side-effects, academic and occupational impairment, and serious relationship problems. The majority of previous studies on Internet addiction disorders (IAD) have focused on structural and functional abnormalities, while few studies have simultaneously investigated the structural and functional brain alterations underlying individual differences in IA tendencies measured by questionnaires in a healthy sample. Here we combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity, rsFC) information to explore the neural mechanisms underlying IAT in a large sample of 260 healthy young adults. The results showed that IAT scores were significantly and positively correlated with rGMV in the right dorsolateral prefrontal cortex (DLPFC, one key node of the cognitive control network, CCN), which might reflect reduced functioning of inhibitory control. More interestingly, decreased anticorrelations between the right DLPFC and the medial prefrontal cortex/rostral anterior cingulate cortex (mPFC/rACC, one key node of the default mode network, DMN) were associated with higher IAT scores, which might be associated with reduced efficiency of the CCN and DMN (e.g., diminished cognitive control and self-monitoring). Furthermore, the Stroop interference effect was positively associated with the volume of the DLPFC and with the IA scores, as well as with the connectivity between DLPFC and mPFC, which further indicated that rGMV variations in the DLPFC and decreased anticonnections between the DLPFC and mPFC may reflect addiction-related reduced inhibitory control and cognitive efficiency. These findings suggest the combination of structural and functional information can provide a valuable basis for further understanding of the mechanisms and pathogenesis of IA. PMID:25698637

  7. Retrospective Analysis of Levetiracetam Compared to Phenytoin for Seizure Prophylaxis in Adults with Traumatic Brain Injury

    PubMed Central

    Caballero, G. Christina; Hughes, Darrel W.; Maxwell, Pamela R.; Green, Kay; Gamboa, Conrado D.; Barthol, Colleen A.

    2013-01-01

    Background: Phenytoin is standard of care for seizure prophylaxis following traumatic brain injury (TBI). Levetiracetam, an alternative antiepileptic drug, is utilized for seizure prophylaxis despite limited data supporting its use. Objective: Our primary outcome was post-TBI seizure activity measured by electroencephalogram (EEG) for levetiracetam versus phenytoin. Secondary outcomes were length of intensive care unit (ICU) stay, requirement for additional antiepileptic drugs (AED), and drug and monitoring costs. Methods: A retrospective review was performed of patients admitted to neurosurgical or surgical trauma ICU. Adult patients with at least 1 day of EEG monitoring were included. Patients were excluded if they had history of epilepsy, prior TBI, less than 48 hours of AED therapy, or additional AED prior to EEG monitoring. Results: A total 90 patients met inclusion criteria, with 18 receiving levetiracetam and 72 receiving phenytoin. Prevalence of EEG-confirmed seizure activity was similar between the levetiracetam and phenytoin groups (28% vs 29%; P = .99). ICU length of stay (13 vs 18 days; P = .28), time to EEG-confirmed seizure activity (4 vs 6 days; P = .24), and duration of seizure prophylaxis (9 vs 14 days; P = .18) were also similar. The median daily cost of levetiracetam therapy was $43 compared to $55 for phenytoin therapy and monitoring (P = .08). When all anticonvulsant therapy and monitoring were included, costs were lower for the levetiracetam group ($45 vs $83; P = .02). Conclusion: Levetiracetam may provide an alternative treatment option for seizure prevention in TBI patients in the ICU. Total antiepileptic drug and monitoring costs were lower for levetiracetam patients. PMID:24421550

  8. That's Using Your Brain!

    ERIC Educational Resources Information Center

    Visser, Dana R.

    1996-01-01

    Discusses new adult learning theories, including those of Roger Sperry (left brain/right brain), Paul McLean (triune brain), and Howard Gardner (multiple intelligences). Relates adult learning theory to training. (JOW)

  9. Statistical learning of recurring sound patterns encodes auditory objects in songbird forebrain

    PubMed Central

    Lu, Kai; Vicario, David S.

    2014-01-01

    Auditory neurophysiology has demonstrated how basic acoustic features are mapped in the brain, but it is still not clear how multiple sound components are integrated over time and recognized as an object. We investigated the role of statistical learning in encoding the sequential features of complex sounds by recording neuronal responses bilaterally in the auditory forebrain of awake songbirds that were passively exposed to long sound streams. These streams contained sequential regularities, and were similar to streams used in human infants to demonstrate statistical learning for speech sounds. For stimulus patterns with contiguous transitions and with nonadjacent elements, single and multiunit responses reflected neuronal discrimination of the familiar patterns from novel patterns. In addition, discrimination of nonadjacent patterns was stronger in the right hemisphere than in the left, and may reflect an effect of top-down modulation that is lateralized. Responses to recurring patterns showed stimulus-specific adaptation, a sparsening of neural activity that may contribute to encoding invariants in the sound stream and that appears to increase coding efficiency for the familiar stimuli across the population of neurons recorded. As auditory information about the world must be received serially over time, recognition of complex auditory objects may depend on this type of mnemonic process to create and differentiate representations of recently heard sounds. PMID:25246563

  10. Statistical learning of recurring sound patterns encodes auditory objects in songbird forebrain.

    PubMed

    Lu, Kai; Vicario, David S

    2014-10-01

    Auditory neurophysiology has demonstrated how basic acoustic features are mapped in the brain, but it is still not clear how multiple sound components are integrated over time and recognized as an object. We investigated the role of statistical learning in encoding the sequential features of complex sounds by recording neuronal responses bilaterally in the auditory forebrain of awake songbirds that were passively exposed to long sound streams. These streams contained sequential regularities, and were similar to streams used in human infants to demonstrate statistical learning for speech sounds. For stimulus patterns with contiguous transitions and with nonadjacent elements, single and multiunit responses reflected neuronal discrimination of the familiar patterns from novel patterns. In addition, discrimination of nonadjacent patterns was stronger in the right hemisphere than in the left, and may reflect an effect of top-down modulation that is lateralized. Responses to recurring patterns showed stimulus-specific adaptation, a sparsening of neural activity that may contribute to encoding invariants in the sound stream and that appears to increase coding efficiency for the familiar stimuli across the population of neurons recorded. As auditory information about the world must be received serially over time, recognition of complex auditory objects may depend on this type of mnemonic process to create and differentiate representations of recently heard sounds. PMID:25246563

  11. Influence of Testosterone Metabolites on Song-Control System Neuroplasticity during Photostimulation in Adult European Starlings (Sturnus vulgaris)

    PubMed Central

    Hall, Zachary J.; MacDougall-Shackleton, Scott A.

    2012-01-01

    The song-control system is a network of discrete nuclei in the songbird brain that controls the production and learning of birdsong and exhibits some of the best-studied neuroplasticity found in the adult brain. Photoperiodic growth of the song-control system during the breeding season is driven, at least in part, by the gonadal steroid testosterone. When acting on neural tissue, however, testosterone can be metabolized into 5α-dihydrotestosterone (DHT) or 17β-estradiol (E2), which activate different hormonal signaling pathways. By treating adult starlings with both testosterone metabolites and metabolite antagonists, we attempted to isolate the effects of androgen and estrogen treatment on neuroplasticity during photostimulation in male and female European starlings (Sturnus vulgaris). Photostimulation resulted in a large HVC volume typical of the breeding season in all treatments independent of hormone treatment. E2 had additional effects on HVC growth by reducing neuron density and enhancing early survival of new neurons recruited to HVC in females but did not significantly affect HVC volume. Conversely, DHT reduced the migration of new neurons, assessed by the expression of doublecortin, to HVC. DHT also increased syrinx mass and maintained RA (robust nucleus of the arcopallium) cytoarchitecture in the presence of aromatase inhibitors. In addition, we document the first evidence of sex-specific neuroplastic responses of the song-control system to androgens and estrogens. These findings suggest that the contributions of DHT and E2 signaling in songbird neuroplasticity may be regulated by photoperiod and that future studies should account for species and sex differences in the brain. PMID:22792214

  12. Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

    PubMed

    Roman-Urrestarazu, Andres; Lindholm, Päivi; Moilanen, Irma; Kiviniemi, Vesa; Miettunen, Jouko; Jääskeläinen, Erika; Mäki, Pirjo; Hurtig, Tuula; Ebeling, Hanna; Barnett, Jennifer H; Nikkinen, Juha; Suckling, John; Jones, Peter B; Veijola, Juha; Murray, Graham K

    2016-05-01

    When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time. PMID:26307356

  13. Predicting healthy older adult's brain age based on structural connectivity networks using artificial neural networks.

    PubMed

    Lin, Lan; Jin, Cong; Fu, Zhenrong; Zhang, Baiwen; Bin, Guangyu; Wu, Shuicai

    2016-03-01

    Brain ageing is followed by changes of the connectivity of white matter (WM) and changes of the grey matter (GM) concentration. Neurodegenerative disease is more vulnerable to an accelerated brain ageing, which is associated with prospective cognitive decline and disease severity. Accurate detection of accelerated ageing based on brain network analysis has a great potential for early interventions designed to hinder atypical brain changes. To capture the brain ageing, we proposed a novel computational approach for modeling the 112 normal older subjects (aged 50-79 years) brain age by connectivity analyses of networks of the brain. Our proposed method applied principal component analysis (PCA) to reduce the redundancy in network topological parameters. Back propagation artificial neural network (BPANN) improved by hybrid genetic algorithm (GA) and Levenberg-Marquardt (LM) algorithm is established to model the relation among principal components (PCs) and brain age. The predicted brain age is strongly correlated with chronological age (r=0.8). The model has mean absolute error (MAE) of 4.29 years. Therefore, we believe the method can provide a possible way to quantitatively describe the typical and atypical network organization of human brain and serve as a biomarker for presymptomatic detection of neurodegenerative diseases in the future. PMID:26718834

  14. Factors affecting songbird nest survival in riparian forests in a Midwestern agricultural landscape

    USGS Publications Warehouse

    Peak, R.G.; Thompson, F. R., III; Shaffer, T.L.

    2004-01-01

    We investigated factors affecting nest success of songbirds in riparian forest and buffers in northeastern Missouri. We used an information-theoretic approach to determine support for hypotheses concerning effects of nest-site, habitat-patch, edge, and temporal factors on nest success of songbirds in three narrow (55DS95 m) and three wide (400DS530 m) riparian forests with adjacent grasslandDSshrub buffer strips and in three narrow and three wide riparian forests without adjacent grasslandDSshrub buffer strips. We predicted that temporal effects would have the most support and that habitat-patch and edge effects would have little support, because nest predation would be great across all sites in the highly fragmented, predominantly agricultural landscape. Interval nest success was 0.404, 0.227, 0.070, and 0.186, respectively, for Gray Catbird (Dumetella carolinensis), Northern Cardinal (Cardinalis cardinalis), Indigo Bunting (Passerina cyanea), and forest interior species pooled (Acadian Flycatcher [Empidonax virescens], Wood Thrush [Hylocichla mustelina], Ovenbird [Seiurus aurocapillus], and Kentucky Warbler [Oporornis formosus]). The effect of nest stage on nest success had the most support; daily nest success for Gray Catbird and Indigo Bunting were lowest in the laying stage. We found strong support for greater nest success of Gray Catbird in riparian forests with adjacent buffer strips than in riparian forests without adjacent buffer strips. Patch width also occurred in the most supported model for Gray Catbird, but with very limited support. The null model received the most support for Northern Cardinal. Riparian forests provided breeding habitat for areas sensitive forest species and grassland-shrub nesting species. Buffer strips provided additional breeding habitat for grassland-shrub nesting species. Interval nest success for Indigo Bunting and area-sensitive forest species pooled, however, fell well below the level that is likely necessary to balance

  15. Factors affecting songbird nest survival in riparian forests in a midwestern agricultural landscape

    USGS Publications Warehouse

    Peak, R.G.; Thompson, F. R., III; Shaffer, T.L.

    2004-01-01

    We investigated factors affecting nest success of songbirds in riparian forest and buffers in northeastern Missouri. We used an information-theoretic approach to determine support for hypotheses concerning effects of nest-site, habitat-patch, edge, and temporal factors on nest success of songbirds in three narrow (55-95 m) and three wide (400-530 m) riparian forests with adjacent grassland-shrub buffer strips and in three narrow and three wide riparian forests without adjacent grassland-shrub buffer strips. We predicted that temporal effects would have the most support and that habitat-patch and edge effects would have little support, because nest predation would be great across all sites in the highly fragmented, predominantly agricultural landscape. Interval nest success was 0.404, 0.227, 0.070, and 0.186, respectively, for Gray Catbird (Dumetella carolinensis), Northern Cardinal (Cardinalis cardinalis), Indigo Bunting (Passerina cyanea), and forest interior species pooled (Acadian Flycatcher [Empidonax virescens], Wood Thrush [Hylocichla mustelina], Ovenbird [Seiurus aurocapillus], and Kentucky Warbler [Oporornis formosus]). The effect of nest stage on nest success had the most support; daily nest success for Gray Catbird and Indigo Bunting were lowest in the laying stage. We found strong support for greater nest success of Gray Catbird in riparian forests with adjacent buffer strips than in riparian forests without adjacent buffer strips. Patch width also occurred in the most-supported model for Gray Catbird, but with very limited support. The null model received the most support for Northern Cardinal. Riparian forests provided breeding habitat for area-sensitive forest species and grassland-shrub nesting species. Buffer strips provided additional breeding habitat for grassland-shrub nesting species. Interval nest success for Indigo Bunting and area-sensitive forest species pooled, however, fell well below the level that is likely necessary to balance juvenile

  16. Afferents from Vocal Motor and Respiratory Effectors are Recruited during Vocal Production in Juvenile Songbirds

    PubMed Central

    Bottjer, Sarah W.; To, Michelle

    2012-01-01

    Learned behaviors require coordination of diverse sensory inputs with motivational and motor systems. Although mechanisms underlying vocal learning in songbirds have focused primarily on auditory inputs, it is likely that sensory inputs from vocal effectors also provide essential feedback. We investigated the role of somatosensory and respiratory inputs from vocal effectors of juvenile zebra finches (Taeniopygia guttata) during the stage of sensorimotor integration when they are learning to imitate a previously memorized tutor song. We report that song production induced expression of the immediate early gene product Fos in trigeminal regions that receive hypoglossal afferents from the tongue and syrinx (the main vocal organ). Furthermore, unilateral lesion of hypoglossal afferents greatly diminished singing-induced Fos expression on the side ipsilateral to the lesion, but not on the intact control side. In addition, unilateral lesion of the vagus reduced Fos expression in the ipsilateral nucleus of the solitary tract in singing birds. Lesion of the hypoglossal nerve to the syrinx greatly disrupted vocal behavior, whereas lesion of the hypoglossal nerve to the tongue exerted no obvious disruption and lesions of the vagus caused some alterations to song behavior. These results provide the first functional evidence that somatosensory and respiratory feedback from peripheral effectors is activated during vocal production and conveyed to brainstem regions. Such feedback is likely to play an important role in vocal learning during sensorimotor integration in juvenile birds and in maintaining stereotyped vocal behavior in adults. PMID:22875924

  17. Effects of nocturnal illumination on life-history decisions and fitness in two wild songbird species

    PubMed Central

    de Jong, Maaike; Ouyang, Jenny Q.; Da Silva, Arnaud; van Grunsven, Roy H. A.; Kempenaers, Bart; Visser, Marcel E.; Spoelstra, Kamiel

    2015-01-01

    The effects of artificial night lighting on animal behaviour and fitness are largely unknown. Most studies report short-term consequences in locations that are also exposed to other anthropogenic disturbance. We know little about how the effects of nocturnal illumination vary with different light colour compositions. This is increasingly relevant as the use of LED lights becomes more common, and LED light colour composition can be easily adjusted. We experimentally illuminated previously dark natural habitat with white, green and red light, and measured the effects on life-history decisions and fitness in two free-living songbird species, the great tit (Parus major) and pied flycatcher (Ficedula hypoleuca) in two consecutive years. In 2013, but not in 2014, we found an effect of light treatment on lay date, and of the interaction of treatment and distance to the nearest lamp post on chick mass in great tits but not in pied flycatchers. We did not find an effect in either species of light treatment on breeding densities, clutch size, probability of brood failure, number of fledglings and adult survival. The finding that light colour may have differential effects opens up the possibility to mitigate negative ecological effects of nocturnal illumination by using different light spectra. PMID:25780240

  18. Effects of nocturnal illumination on life-history decisions and fitness in two wild songbird species.

    PubMed

    de Jong, Maaike; Ouyang, Jenny Q; Da Silva, Arnaud; van Grunsven, Roy H A; Kempenaers, Bart; Visser, Marcel E; Spoelstra, Kamiel

    2015-05-01

    The effects of artificial night lighting on animal behaviour and fitness are largely unknown. Most studies report short-term consequences in locations that are also exposed to other anthropogenic disturbance. We know little about how the effects of nocturnal illumination vary with different light colour compositions. This is increasingly relevant as the use of LED lights becomes more common, and LED light colour composition can be easily adjusted. We experimentally illuminated previously dark natural habitat with white, green and red light, and measured the effects on life-history decisions and fitness in two free-living songbird species, the great tit (Parus major) and pied flycatcher (Ficedula hypoleuca) in two consecutive years. In 2013, but not in 2014, we found an effect of light treatment on lay date, and of the interaction of treatment and distance to the nearest lamp post on chick mass in great tits but not in pied flycatchers. We did not find an effect in either species of light treatment on breeding densities, clutch size, probability of brood failure, number of fledglings and adult survival. The finding that light colour may have differential effects opens up the possibility to mitigate negative ecological effects of nocturnal illumination by using different light spectra. PMID:25780240

  19. Neural FoxP2 and FoxP1 expression in the budgerigar, an avian species with adult vocal learning

    PubMed Central

    Hara, Erina; Perez, Jemima M.; Whitney, Osceola; Chen, Qianqian; White, Stephanie A.; Wright, Timothy F.

    2015-01-01

    Vocal learning underlies acquisition of both language in humans and vocal signals in some avian taxa. These bird groups and humans exhibit convergent developmental phases and associated brain pathways for vocal communication. The transcription factor FoxP2 plays critical roles in vocal learning in humans and songbirds. Another member of the forkhead box gene family, FoxP1 also shows high expression in brain areas involved in vocal learning and production. Here, we investigate FoxP2 and FoxP1 mRNA and protein in adult male budgerigars (Melopsittacus undulatus), a parrot species that exhibits vocal learning as both juveniles and adults. To examine these molecules in adult vocal learners, we compared their expression patterns in the budgerigar striatal nucleus involved in vocal learning, magnocellular nucleus of the medial striatum (MMSt), across birds with different vocal states, such as vocalizing to a female (directed), vocalizing alone (undirected), and non-vocalizing. We found that both FoxP2 mRNA and protein expressions were consistently lower in MMSt than in the adjacent striatum regardless of the vocal states, whereas previous work has shown that songbirds exhibit downregulation in the homologous region, Area X, only after singing alone. In contrast, FoxP1 levels were high in MMSt compared to the adjacent striatum in all groups. Taken together these results strengthen the general hypothesis that FoxP2 and FoxP1 have specialized expression in vocal nuclei across a range of taxa, and suggest that the adult vocal plasticity seen in budgerigars may be a product of persistent down-regulation of FoxP2 in MMSt. PMID:25601574

  20. Neural FoxP2 and FoxP1 expression in the budgerigar, an avian species with adult vocal learning.

    PubMed

    Hara, Erina; Perez, Jemima M; Whitney, Osceola; Chen, Qianqian; White, Stephanie A; Wright, Timothy F

    2015-04-15

    Vocal learning underlies acquisition of both language in humans and vocal signals in some avian taxa. These bird groups and humans exhibit convergent developmental phases and associated brain pathways for vocal communication. The transcription factor FoxP2 plays critical roles in vocal learning in humans and songbirds. Another member of the forkhead box gene family, FoxP1 also shows high expression in brain areas involved in vocal learning and production. Here, we investigate FoxP2 and FoxP1 mRNA and protein in adult male budgerigars (Melopsittacus undulatus), a parrot species that exhibits vocal learning as both juveniles and adults. To examine these molecules in adult vocal learners, we compared their expression patterns in the budgerigar striatal nucleus involved in vocal learning, magnocellular nucleus of the medial striatum (MMSt), across birds with different vocal states, such as vocalizing to a female (directed), vocalizing alone (undirected), and non-vocalizing. We found that both FoxP2 mRNA and protein expressions were consistently lower in MMSt than in the adjacent striatum regardless of the vocal states, whereas previous work has shown that songbirds exhibit down-regulation in the homologous region, Area X, only after singing alone. In contrast, FoxP1 levels were high in MMSt compared to the adjacent striatum in all groups. Taken together these results strengthen the general hypothesis that FoxP2 and FoxP1 have specialized expression in vocal nuclei across a range of taxa, and suggest that the adult vocal plasticity seen in budgerigars may be a product of persistent down-regulation of FoxP2 in MMSt. PMID:25601574

  1. Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology.

    PubMed

    Bowling, Heather; Bhattacharya, Aditi; Klann, Eric; Chao, Moses V

    2016-03-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plasticity, learning and memory, and in preventing neurodegeneration. Despite decades of investigations into downstream signaling cascades and changes in cellular processes, the mechanisms of how BDNF reshapes circuits in vivo remain unclear. This informational gap partly arises from the fact that the bulk of studies into the molecular actions of BDNF have been performed in dissociated neuronal cultures, while the majority of studies on synaptic plasticity, learning and memory were performed in acute brain slices or in vivo. A recent study by Bowling-Bhattacharya et al., measured the proteomic changes in acute adult hippocampal slices following treatment and reported changes in proteins of neuronal and non-neuronal origin that may in concert modulate synaptic release and secretion in the slice. In this paper, we place these findings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain. PMID:27127458

  2. Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology

    PubMed Central

    Bowling, Heather; Bhattacharya, Aditi; Klann, Eric; Chao, Moses V.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plasticity, learning and memory, and in preventing neurodegeneration. Despite decades of investigations into downstream signaling cascades and changes in cellular processes, the mechanisms of how BDNF reshapes circuits in vivo remain unclear. This informational gap partly arises from the fact that the bulk of studies into the molecular actions of BDNF have been performed in dissociated neuronal cultures, while the majority of studies on synaptic plasticity, learning and memory were performed in acute brain slices or in vivo. A recent study by Bowling-Bhattacharya et al., measured the proteomic changes in acute adult hippocampal slices following treatment and reported changes in proteins of neuronal and non-neuronal origin that may in concert modulate synaptic release and secretion in the slice. In this paper, we place these findings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain. PMID:27127458

  3. Brain Gray Matter Changes Associated with Mindfulness Meditation in Older Adults: An Exploratory Pilot Study using Voxel-based Morphometry

    PubMed Central

    Kurth, Florian; Luders, Eileen; Wu, Brian; Black, David S.

    2015-01-01

    Background Mindfulness-based interventions (MBIs) have previously been associated with structural gray matter changes in normal healthy adults. However, it remains unknown if standardized MBIs can induce similar changes in older adults and those with health complaints as well. The objective of this investigation was to examine the effect of a standardized MBI on the gray matter tissue of older adults with sleep disturbances. Methods This exploratory single-group pilot longitudinal study examined local gray matter changes over a six-week MBI period. Participants included six older adult community volunteers (M=66.5 years of age, SD=5.5, range=58–75; 66% female) with sleep disturbances recruited through advertisement in local newspapers/flyers posted at a university medical center and affiliated clinics in Los Angeles, CA. The MBI was delivered as a weekly, two-hour, six-session, group-based course in mindfulness meditation. Gray matter was measured voxel-wise pre- and post-intervention. Results A significant gray matter increase was identified within the precuneus, possibly implicating meditation-induced changes of the default mode network. In contrast, observed significant gray matter decreases may have been driven by MBI-related remediation of brain architecture subserving sleep complaints. Conclusions Exploratory findings suggest that mindfulness meditation practice is associated with a detectable alteration of cerebral gray matter in older adults. PMID:25632405

  4. Allowable levels of take for the trade in Nearctic songbirds

    USGS Publications Warehouse

    Johnson, Fred A.; Walters, Matthew A.H.; Boomer, G. Scott

    2012-01-01

    The take of Nearctic songbirds for the caged-bird trade is an important cultural and economic activity in Mexico, but its sustainability has been questioned. We relied on the theta-logistic population model to explore options for setting allowable levels of take for 11 species of passerines that were subject to legal take in Mexico in 2010. Because estimates of population size necessary for making periodic adjustments to levels of take are not routinely available, we examined the conditions under which a constant level of take might contribute to population depletion (i.e., a population below its level of maximum net productivity). The chance of depleting a population is highest when levels of take are based on population sizes that happen to be much lower or higher than the level of maximum net productivity, when environmental variation is relatively high and serially correlated, and when the interval between estimation of population size is relatively long (≥5 years). To estimate demographic rates of songbirds involved in the Mexican trade we relied on published information and allometric relationships to develop probability distributions for key rates, and then sampled from those distributions to characterize the uncertainty in potential levels of take. Estimates of the intrinsic rate of growth (r) were highly variable, but median estimates were consistent with those expected for relatively short-lived, highly fecund species. Allowing for the possibility of nonlinear density dependence generally resulted in allowable levels of take that were lower than would have been the case under an assumption of linearity. Levels of take authorized by the Mexican government in 2010 for the 11 species we examined were small in comparison to relatively conservative allowable levels of take (i.e., those intended to achieve 50% of maximum sustainable yield). However, the actual levels of take in Mexico are unknown and almost certainly exceed the authorized take. Also, the take

  5. White matter structure in young adults with familial risk for psychosis - The Oulu Brain and Mind Study.

    PubMed

    Koivukangas, Jenni; Björnholm, Lassi; Tervonen, Osmo; Miettunen, Jouko; Nordström, Tanja; Kiviniemi, Vesa; Mäki, Pirjo; Jääskeläinen, Erika; Mukkala, Sari; Moilanen, Irma; Barnett, Jennifer H; Jones, Peter B; Nikkinen, Juha; Veijola, Juha

    2015-09-30

    According to the disconnectivity model, disruptions in neural connectivity play an essential role in the pathology of schizophrenia. The aim of this study was to determine whether these abnormalities are present in young adults with familial risk (FR) for psychosis in the general population based sample. We used diffusion tensor imaging (DTI) and tract-based spatial statistics to compare whole-brain fractional anisotropy, mean diffusivity, and axial and radial diffusion in 47 (17 males) FR subjects to 51 controls (17 males). All the participants were aged between 20 and 25 years and were members of the Northern Finland Birth Cohort 1986 (Oulu Brain and Mind Study). Region of interest analyses were conducted for 12 tracts. Separately, we analysed whole-brain FA for the subgroup with FR for schizophrenia (n=13) compared with 13 gender-matched controls. Contrary to our expectations there were no differences in any of the DTI measures between FR and control groups. This suggests that white matter abnormalities may not be a genetic feature for risk of psychosis and preceding the onset of a psychotic disorder. Our findings do not support the theory of disconnectivity as a primary sign of psychosis in young adults with FR for the illness. PMID:26231121

  6. Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global - disturbed local network organization.

    PubMed

    Sidlauskaite, Justina; Caeyenberghs, Karen; Sonuga-Barke, Edmund; Roeyers, Herbert; Wiersema, Jan R

    2015-01-01

    Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits. PMID:26640763

  7. The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

    NASA Astrophysics Data System (ADS)

    Zhang, Ning

    A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility

  8. Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

    USGS Publications Warehouse

    Strobl-Mazzulla, P. H.; Lethimonier, C.; Gueguen, M.M.; Karube, M.; Fernandino, J.I.; Yoshizaki, G.; Patino, R.; Strussmann, C.A.; Kah, O.; Somoza, G.M.

    2008-01-01

    Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, ?? and ??, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor ??, but not ??, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate. ?? 2008 Elsevier Inc.

  9. Finding the Beat: From Socially Coordinated Vocalizations in Songbirds to Rhythmic Entrainment in Humans

    PubMed Central

    Benichov, Jonathan I.; Globerson, Eitan; Tchernichovski, Ofer

    2016-01-01

    Humans and oscine songbirds share the rare capacity for vocal learning. Songbirds have the ability to acquire songs and calls of various rhythms through imitation. In several species, birds can even coordinate the timing of their vocalizations with other individuals in duets that are synchronized with millisecond-accuracy. It is not known, however, if songbirds can perceive rhythms holistically nor if they are capable of spontaneous entrainment to complex rhythms, in a manner similar to humans. Here we review emerging evidence from studies of rhythm generation and vocal coordination across songbirds and humans. In particular, recently developed experimental methods have revealed neural mechanisms underlying the temporal structure of song and have allowed us to test birds' abilities to predict the timing of rhythmic social signals. Surprisingly, zebra finches can readily learn to anticipate the calls of a “vocal robot” partner and alter the timing of their answers to avoid jamming, even in reference to complex rhythmic patterns. This capacity resembles, to some extent, human predictive motor response to an external beat. In songbirds, this is driven, at least in part, by the forebrain song system, which controls song timing and is essential for vocal learning. Building upon previous evidence for spontaneous entrainment in human and non-human vocal learners, we propose a comparative framework for future studies aimed at identifying shared mechanism of rhythm production and perception across songbirds and humans. PMID:27375455

  10. Tectonic collision and uplift of Wallacea triggered the global songbird radiation.

    PubMed

    Moyle, Robert G; Oliveros, Carl H; Andersen, Michael J; Hosner, Peter A; Benz, Brett W; Manthey, Joseph D; Travers, Scott L; Brown, Rafe M; Faircloth, Brant C

    2016-01-01

    Songbirds (oscine passerines) are the most species-rich and cosmopolitan bird group, comprising almost half of global avian diversity. Songbirds originated in Australia, but the evolutionary trajectory from a single species in an isolated continent to worldwide proliferation is poorly understood. Here, we combine the first comprehensive genome-scale DNA sequence data set for songbirds, fossil-based time calibrations, and geologically informed biogeographic reconstructions to provide a well-supported evolutionary hypothesis for the group. We show that songbird diversification began in the Oligocene, but accelerated in the early Miocene, at approximately half the age of most previous estimates. This burst of diversification occurred coincident with extensive island formation in Wallacea, which provided the first dispersal corridor out of Australia, and resulted in independent waves of songbird expansion through Asia to the rest of the globe. Our results reconcile songbird evolution with Earth history and link a major radiation of terrestrial biodiversity to early diversification within an isolated Australian continent. PMID:27575437

  11. Songbird migration across the Sahara: the non-stop hypothesis rejected!

    PubMed

    Schmaljohann, Heiko; Liechti, Felix; Bruderer, Bruno

    2007-03-01

    Billions of songbirds breeding in the Western Palaearctic cross the largest desert of the world, the Sahara, twice a year. While crossing Europe, the vast majority use an intermittent flight strategy, i.e. fly at night and rest or feed during the day. However, it was long assumed that they overcome the Sahara in a 40 h non-stop flight. In this study, we observed bird migration with radar in the plain sand desert of the Western Sahara (Mauritania) during autumn and spring migration and revealed a clear prevalence of intermittent migration. Massive departures of songbirds just after sunset independent of site and season suggests strongly that songbirds spent the day in the plain desert. Thus, most songbirds cross the Sahara predominantely by the intermittent flight strategy. Autumn migration took place mainly at low altitudes with high temperatures, its density decreased abruptly before sunrise, followed by very little daytime migration. Migration was highly restricted to night-time and matched perfectly the intermittent flight strategy. However, in spring, when migratory flights occurred at much higher altitudes than in autumn, in cool air, about 17% of the songbird migration occurred during the day. This suggests that flying in high temperatures and turbulent air, as is the case in autumn, may lead to an increase in water and/or energy loss and may prevent songbirds from prolonged flights into the day. PMID:17254999

  12. Finding the Beat: From Socially Coordinated Vocalizations in Songbirds to Rhythmic Entrainment in Humans.

    PubMed

    Benichov, Jonathan I; Globerson, Eitan; Tchernichovski, Ofer

    2016-01-01

    Humans and oscine songbirds share the rare capacity for vocal learning. Songbirds have the ability to acquire songs and calls of various rhythms through imitation. In several species, birds can even coordinate the timing of their vocalizations with other individuals in duets that are synchronized with millisecond-accuracy. It is not known, however, if songbirds can perceive rhythms holistically nor if they are capable of spontaneous entrainment to complex rhythms, in a manner similar to humans. Here we review emerging evidence from studies of rhythm generation and vocal coordination across songbirds and humans. In particular, recently developed experimental methods have revealed neural mechanisms underlying the temporal structure of song and have allowed us to test birds' abilities to predict the timing of rhythmic social signals. Surprisingly, zebra finches can readily learn to anticipate the calls of a "vocal robot" partner and alter the timing of their answers to avoid jamming, even in reference to complex rhythmic patterns. This capacity resembles, to some extent, human predictive motor response to an external beat. In songbirds, this is driven, at least in part, by the forebrain song system, which controls song timing and is essential for vocal learning. Building upon previous evidence for spontaneous entrainment in human and non-human vocal learners, we propose a comparative framework for future studies aimed at identifying shared mechanism of rhythm production and perception across songbirds and humans. PMID:27375455

  13. Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial.

    PubMed

    Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M; Waterworth, John

    2014-01-01

    Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others. PMID:25352805

  14. Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial

    PubMed Central

    Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M.; Waterworth, John

    2014-01-01

    Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others. PMID:25352805

  15. Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

    PubMed

    Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

    2016-10-01

    Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner. PMID:27317840

  16. Circulating Omega‐3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study

    PubMed Central

    Virtanen, Jyrki K.; Siscovick, David S.; Lemaitre, Rozenn N.; Longstreth, William T.; Spiegelman, Donna; Rimm, Eric B.; King, Irena B.; Mozaffarian, Dariush

    2013-01-01

    Background Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results In the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake. Conclusions Among older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation. PMID:24113325

  17. Mesoscopic Patterns of Neural Activity Support Songbird Cortical Sequences

    PubMed Central

    Guitchounts, Grigori; Velho, Tarciso; Lois, Carlos; Gardner, Timothy J.

    2015-01-01

    Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From “time cells” in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia–projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song. PMID:26039895

  18. Mesoscopic patterns of neural activity support songbird cortical sequences.

    PubMed

    Markowitz, Jeffrey E; Liberti, William A; Guitchounts, Grigori; Velho, Tarciso; Lois, Carlos; Gardner, Timothy J

    2015-06-01

    Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From "time cells" in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia-projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song. PMID:26039895

  19. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    <