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Sample records for adult murine brain

  1. Extracellular proteolysis in the adult murine brain.

    PubMed

    Sappino, A P; Madani, R; Huarte, J; Belin, D; Kiss, J Z; Wohlwend, A; Vassalli, J D

    1993-08-01

    Plasminogen activators are important mediators of extracellular metabolism. In the nervous system, plasminogen activators are thought to be involved in the remodeling events required for cell migration during development and regeneration. We have now explored the expression of the plasminogen activator/plasmin system in the adult murine central nervous system. Tissue-type plasminogen activator is synthesized by neurons of most brain regions, while prominent tissue-type plasminogen activator-catalyzed proteolysis is restricted to discrete areas, in particular within the hippocampus and hypothalamus. Our observations indicate that tissue-type plasminogen activator-catalyzed proteolysis in neural tissues is not limited to ontogeny, but may also contribute to adult central nervous system physiology, for instance by influencing neuronal plasticity and synaptic reorganization. The identification of an extracellular proteolytic system active in the adult central nervous system may also help gain insights into the pathogeny of neurodegenerative disorders associated with extracellular protein deposition.

  2. Effects of the murine skull in optoacoustic brain microscopy.

    PubMed

    Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

    2016-01-01

    Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments.

  3. Interleukin 6 promotes vasculogenesis of murine brain microvessel endothelial cells.

    PubMed

    Fee, D; Grzybicki, D; Dobbs, M; Ihyer, S; Clotfelter, J; Macvilay, S; Hart, M N; Sandor, M; Fabry, Z

    2000-06-01

    Interleukin 6 (IL-6) is a cytokine that acts on a wide range of tissues influencing cell growth and differentiation. Here we show that IL-6 plays a role in the early vascular development (vasculogenesis) in the central nervous system (CNS). We report that IL-6 induces the proliferation of brain microvascular endothelial cells in vitro. Furthermore, IL-6 significantly accelerates the formation of tube-like structures by these cells in Matrigel basement matrix. Moreover, IL-6 mRNA is expressed in vivo in two physiological conditions in which vascularization in the CNS is important: (1) during normal brain development, (2) during the healing process of a traumatic brain injury. Expression of IL-6 mRNA coincides with the expression of vascular endothelial growth factor (VEGF) mRNA in the developing brain with decreasing expression following birth. However, IL-6 mRNA can be detected in the healing adult murine brain tissue by in situ hybridization coinciding with the period of intense tissue reorganization. The transient upregulation of IL-6 mRNA during normal brain development and at brain injury site and the effect of IL-6 on in vitro vasculogenesis suggest that IL-6 may play a role in normal physiology of vascularization in the CNS.

  4. Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Wolgemuth, D. J.

    1996-01-01

    We have examined the spatial pattern of expression of a member of the hsp70 gene family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot analysis and in situ hybridization revealed abundant expression of an 'antisense' hsp70.2 transcript in several areas of adult mouse brain. Two different transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene were expressed in distinct and only partially overlapping neuronal populations. RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in several areas of the brain, with highest signal in the hippocampus. Abundant expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was detected in several brain regions, notably in the brainstem, cerebellum, mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization revealed that the sense and antisense transcripts were both predominantly neuronal and localized to the same cell types in the granular layer of the cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells. Our findings have revealed a distinct cellular and spatial localization of both sense and antisense transcripts, demonstrating a new level of complexity in the function of the heat shock genes.

  5. 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 ...

  6. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  7. Mapping of neurotrophins and their receptors in the adult mouse brain and their role in the pathogenesis of a transgenic murine model of bovine spongiform encephalopathy.

    PubMed

    Marco-Salazar, P; Márquez, M; Fondevila, D; Rabanal, R M; Torres, J M; Pumarola, M; Vidal, E

    2014-05-01

    Neurotrophins are a family of growth factors that act on neuronal cells. The neurotrophins include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3, -4 and -5. The action of neurotrophins depends on two transmembrane-receptor signalling systems: (1) the tropomyosin-related kinase (Trk) family of tyrosine kinase receptors (Trk A, Trk B and Trk C) and (2) the p75 neurotrophin receptor (p75(NTR)). The interaction between neurotrophic factors and their receptors may be involved in the mechanisms that regulate the differential susceptibility of neuronal populations in neurodegenerative diseases. The aim of the present study was to evaluate the role of neurotrophins in the pathogenesis of bovine spongiform encephalopathy (BSE) using a transgenic mouse overexpressing bovine prnp (BoTg 110). Histochemistry for Lycopersicum esculentum agglutinin, haematoxylin and eosin staining and immunohistochemistry for the abnormal isoform of the prion protein (PrP(d)), glial fibrillary acidic protein (GFAP), NGF, BDNF, NT-3 and the receptors Trk A, Trk B, Trk C and p75(NTR) was performed. The lesions and the immunolabelling patterns were assessed semiquantitatively in different areas of the brain. No significant differences in the immunolabelling of neurotrophins and their receptors were observed between BSE-inoculated and control animals, except for p75(NTR), which showed increased expression correlating with the distribution of lesions, PrP(d) deposition and gliosis in the BSE-inoculated mice.

  8. Imatinib treatment reduces brain injury in a murine model of traumatic brain injury

    PubMed Central

    Su, Enming J.; Fredriksson, Linda; Kanzawa, Mia; Moore, Shannon; Folestad, Erika; Stevenson, Tamara K.; Nilsson, Ingrid; Sashindranath, Maithili; Schielke, Gerald P.; Warnock, Mark; Ragsdale, Margaret; Mann, Kris; Lawrence, Anna-Lisa E.; Medcalf, Robert L.; Eriksson, Ulf; Murphy, Geoffrey G.; Lawrence, Daniel A.

    2015-01-01

    Current therapies for Traumatic brain injury (TBI) focus on stabilizing individuals and on preventing further damage from the secondary consequences of TBI. A major complication of TBI is cerebral edema, which can be caused by the loss of blood brain barrier (BBB) integrity. Recent studies in several CNS pathologies have shown that activation of latent platelet derived growth factor-CC (PDGF-CC) within the brain can promote BBB permeability through PDGF receptor α (PDGFRα) signaling, and that blocking this pathway improves outcomes. In this study we examine the efficacy for the treatment of TBI of an FDA approved antagonist of the PDGFRα, Imatinib. Using a murine model we show that Imatinib treatment, begun 45 min after TBI and given twice daily for 5 days, significantly reduces BBB dysfunction. This is associated with significantly reduced lesion size 24 h, 7 days, and 21 days after TBI, reduced cerebral edema, determined from apparent diffusion co-efficient (ADC) measurements, and with the preservation of cognitive function. Finally, analysis of cerebrospinal fluid (CSF) from human TBI patients suggests a possible correlation between high PDGF-CC levels and increased injury severity. Thus, our data suggests a novel strategy for the treatment of TBI with an existing FDA approved antagonist of the PDGFRα. PMID:26500491

  9. Differential zinc transport into testis and brain of cadmium-sensitive and -resistant murine strains.

    PubMed

    King, L M; Banks, W A; George, W J

    2000-01-01

    Recently, we showed that murine strain differences to the testicular toxicity of cadmium (Cd) are the result of variable transport of Cd across the blood-testis barrier. Because Cd is a nonessential trace element, it must be using the transporter for an endogenous substance. The objectives for this study were to determine the natural ligand for the transport system used by Cd to enter testis and brain, and to determine whether the transport of that natural ligand also differs among Cd-sensitive and -resistant murine strains. Because zinc (Zn) and Cd are cations of similar size and charge, and because Cd has been shown to inhibit Zn uptake in a variety of systems, we hypothesized that Cd was using Zn transporters to enter tissues. In this study we characterized Zn transport into the testis and brain of Cd-sensitive and -resistant murine strains. We found that the transport of 65Zn into testis and brain of Cd-resistant A/J mice was significantly reduced compared with that in Cd-sensitive 129/J mice. In 129/J mice, unlabeled CdCl2 significantly reduced 65Zn transport by 56% in testes and by 47% in brain. Pretreatment with Zn had no significant effect on 109Cd transport rates into testes or brain of 129/J or A/J mice, but did reduce the percentage of the injected 109Cd dose in testes of 129/J mice by 44% within 60 minutes. From these results we can conclude that Cd is using transport systems that normally function to regulate Zn levels in testes and brain. Murine strain resistance to the testicular effects of Cd is associated with a concomitant attenuation of the Zn transport system in testis.

  10. Ex vivo micro-CT imaging of murine brain models using non-ionic iodinated contrast

    NASA Astrophysics Data System (ADS)

    Salas Bautista, N.; Martínez-Dávalos, A.; Rodríguez-Villafuerte, M.; Murrieta-Rodríguez, T.; Manjarrez-Marmolejo, J.; Franco-Pérez, J.; Calvillo-Velasco, M. E.

    2014-11-01

    Preclinical investigation of brain tumors is frequently carried out by means of intracranial implantation of brain tumor xenografts or allografts, with subsequent analysis of tumor growth using conventional histopathology. However, very little has been reported on the use contrast-enhanced techniques in micro-CT imaging for the study of malignant brain tumors in small animal models. The aim of this study has been to test a protocol for ex vivo imaging of murine brain models of glioblastoma multiforme (GBM) after treatment with non-ionic iodinated solution, using an in-house developed laboratory micro-CT. We have found that the best compromise between acquisition time and image quality is obtained using a 50 kVp, 0.5 mAs, 1° angular step on a 360 degree orbit acquisition protocol, with 70 μm reconstructed voxel size using the Feldkamp algorithm. With this parameters up to 4 murine brains can be scanned in tandem in less than 15 minutes. Image segmentation and analysis of three sample brains allowed identifying tumor volumes as small as 0.4 mm3.

  11. 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.

  12. 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

  13. Treatment of primary brain tumours in adults.

    PubMed

    McNamara, Shanne

    This article considers the complexities of caring for patients with primary brain tumours. The incidence, classification and clinical signs and symptoms are outlined. Adult patients experience disabling effects as a result of a brain tumour, which is often accompanied by high morbidity and mortality rates. The various treatment options available are summarised. However, for many patients, there are limited curative treatment options and the main focus is palliative care. The nurse's contribution to care and support of these patients and their families is discussed, with the aim of improving their quality of life.

  14. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions.

    PubMed

    Terayama, Hayato; Endo, Hitoshi; Tsukamoto, Hideo; Matsumoto, Koichi; Umezu, Mai; Kanazawa, Teruhisa; Ito, Masatoshi; Sato, Tadayuki; Naito, Munekazu; Kawakami, Satoshi; Fujino, Yasuhiro; Tatemichi, Masayuki; Sakabe, Kou

    2016-01-01

    Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure. PMID:27669271

  15. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions

    PubMed Central

    Terayama, Hayato; Endo, Hitoshi; Tsukamoto, Hideo; Matsumoto, Koichi; Umezu, Mai; Kanazawa, Teruhisa; Ito, Masatoshi; Sato, Tadayuki; Naito, Munekazu; Kawakami, Satoshi; Fujino, Yasuhiro; Tatemichi, Masayuki; Sakabe, Kou

    2016-01-01

    Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure. PMID:27669271

  16. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions.

    PubMed

    Terayama, Hayato; Endo, Hitoshi; Tsukamoto, Hideo; Matsumoto, Koichi; Umezu, Mai; Kanazawa, Teruhisa; Ito, Masatoshi; Sato, Tadayuki; Naito, Munekazu; Kawakami, Satoshi; Fujino, Yasuhiro; Tatemichi, Masayuki; Sakabe, Kou

    2016-09-22

    Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure.

  17. Oatp-associated uptake and toxicity of microcystins in primary murine whole brain cells

    SciTech Connect

    Feurstein, D.; Holst, K.; Fischer, A.; Dietrich, D.R.

    2009-01-15

    Microcystins (MCs) are naturally occurring cyclic heptapeptides that exhibit hepato-, nephro- and possibly neurotoxic effects in mammals. Organic anion transporting polypeptides (rodent Oatp/human OATP) appear to be specifically required for active uptake of MCs into hepatocytes and kidney epithelial cells. Based on symptoms of neurotoxicity in MC-intoxicated patients and the presence of Oatp/OATP at the blood-brain-barrier (BBB) and blood-cerebrospinal-fluid-barrier (BCFB) it is hypothesized that MCs can be transported across the BBB/BCFB in an Oatp/OATP-dependent manner and can induce toxicity in brain cells via inhibition of protein phosphatase (PP). To test these hypotheses, the presence of murine Oatp (mOatp) in primary murine whole brain cells (mWBC) was investigated at the mRNA and protein level. MC transport was tested by exposing mWBCs to three different MC-congeners (MC-LR, -LW, -LF) with/without co-incubation with the OATP/Oatp-substrates taurocholate (TC) and bromosulfophthalein (BSP). Uptake of MCs and cytotoxicity was demonstrated via MC-Western blot analysis, immunocytochemistry, cell viability and PP inhibition assays. All MC congeners bound covalently and inhibited mWBC PP. MC-LF was the most cytotoxic congener followed by -LW and -LR. The lowest toxin concentration significantly reducing mWBC viability after 48 h exposure was 400 nM (MC-LF). Uptake of MCs into mWBCs was inhibited via co-incubation with excess TC (50 and 500 {mu}M) and BSP (50 {mu}M). MC-Western blot analysis demonstrated a concentration-dependent accumulation of MCs. In conclusion, the in vitro data support the assumed MC-congener-dependent uptake in a mOatp-associated manner and cytotoxicity of MCs in primary murine whole brain cells.

  18. Tumors in murine brains studied by grating-based phase contrast microtomography

    NASA Astrophysics Data System (ADS)

    Schulz, Georg; Dominietto, Marco; Kovacs, Zsofia; Schmitz, Rüdiger; Hieber, Simone E.; Thalmann, Peter; Beckmann, Felix; Müller, Bert

    2014-09-01

    Angiogenesis, i.e. the formation of vessels, is one of the key processes during tumor development. The newly formed vessels transport oxygen and nutrients from the healthy tissue to the tumor and gives tumor cells the possibility to replicate. The principle of anti-angiogenic therapy is to block angiogenic process in order to stop tumor growth. The aim of the present study is the investigation of murine glioma vascular architecture at early (7 days), intermediate (10 and 15 days) and late (23 days) stage of growth by means of grating-based phase contrast microtomography. We demonstrate that this technique yields premium contrast between healthy and cancerous parts of murine brain tissues.

  19. Differential expression of murine adult hemoglobins in early ontogeny

    SciTech Connect

    Wawrzyniak, C.J.; Lewis, S.E.; Popp, R.A.

    1985-01-01

    A hemoglobin mutation is described that permits study of the expression of the two adult ..beta..-globin genes throughout fetal and postnatal development. Mice with a mutation at the Hbb/sup s/, ..beta..-globin locus, were used to study the relative levels of ..beta..-s2major and ..beta..-sminor globins specified by the mutant Hbb/sup s2/ haplotype during development. At 11.5 days of gestation ..beta..-sminor comprised over 80% and ..beta..-s2major under 20% of the adult beta-globin. The relative level of ..beta..-sminor decreased through fetal development; at birth ..beta..-sminor represented 33.7% of the ..beta..-globin. The adult values of 71.0% ..beta..-s2major and 29.0% ..beta..-sminor globin are expressed in mice six days after birth. Because the two ..beta..-globin genes are expressed in mice of the Hbb/sup 2s/ haplotype, both the ..beta..-smajor and ..beta..-sminor genes must be expressed in mice of the Hbb/sup s/ haplotype. Expression of the ..beta..-sminor gene is elevated to 35.6% in Hbb/sup s2/ mice that have been bled repeatedly. Thus, the 5' ..beta..-s2major and 3' ..beta..-sminor genes of the Hbb/sup s2/ haplotype and, presumably the 5' ..beta..-smajor and 3' ..beta..-sminor genes of the Hbb/sup s/ haplotype, are regulated independently and are homologous to the 5' ..beta..-dmajor and 3' ..beta..-dminor genes of the Hbb/sup d/ haplotype. Mice of the Hbb/sup s2/ haplotype are better than mice of the Hbb/sup d/ haplotytpe for studying the mechanisms of hemoglobin switching because the Hbb/sup s2/ each of the three embryonic and two adult hemoglobins can be separated by electrophoresis. 17 refs., 3 figs.

  20. Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and Brain

    NASA Astrophysics Data System (ADS)

    Chamberlain, Jeffrey S.; Pearlman, Joel A.; Muzny, Donna M.; Gibbs, Richard A.; Ranier, Joel E.; Reeves, Alice A.; Caskey, C. Thomas

    1988-03-01

    Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.

  1. Membrane configuration optimization for a murine in vitro blood-brain barrier model.

    PubMed

    Wuest, Diane M; Wing, Allison M; Lee, Kelvin H

    2013-01-30

    A powerful experimental tool used to study the dynamic functions of the blood-brain barrier (BBB) is an in vitro cellular based system utilizing cell culture inserts in multi-well plates. Currently, usage of divergent model configurations without explanation of selected variable set points renders data comparisons difficult and limits widespread understanding. This work presents for the first time in literature a comprehensive screening study to optimize membrane configuration, with aims to unveil influential membrane effects on the ability of cerebral endothelial cells to form a tight monolayer. First, primary murine brain endothelial cells and astrocytes were co-cultured in contact and non-contact orientations on membranes of pore diameter sizes ranging from 0.4 μm to 8.0 μm, and the non-contact orientation and smallest pore diameter size were shown to support a significantly tighter monolayer formation. Then, membranes made from polyethylene terephthalate (PET) and polycarbonate (PC) purchased from three different commercial sources were compared, and PET membranes purchased from two manufacturers facilitated a significantly tighter monolayer formation. Models were characterized by transendothelial electrical resistance (TEER), sodium fluorescein permeability, and immunocytochemical labeling of tight junction proteins. Finally, a murine brain endothelial cell line, bEnd.3, was grown on the different membranes, and similar results were obtained with respect to optimal membrane configuration selection. The results and methodology presented here on high throughput 24-well plate inserts can be translated to other BBB systems to advance model understanding.

  2. 3D culture of murine neural stem cells on decellularized mouse brain sections.

    PubMed

    De Waele, Jorrit; Reekmans, Kristien; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

    2015-02-01

    Transplantation of neural stem cells (NSC) in diseased or injured brain tissue is widely studied as a potential treatment for various neurological pathologies. However, effective cell replacement therapy relies on the intrinsic capacity of cellular grafts to overcome hypoxic and/or immunological barriers after transplantation. In this context, it is hypothesized that structural support for grafted NSC will be of utmost importance. With this study, we present a novel decellularization protocol for 1.5 mm thick mouse brain sections, resulting in the generation of acellular three-dimensional (3D) brain sections. Next, the obtained 3D brain sections were seeded with murine NSC expressing both the eGFP and luciferase reporter proteins (NSC-eGFP/Luc). Using real-time bioluminescence imaging, the survival and growth of seeded NSC-eGFP/Luc cells was longitudinally monitored for 1-7 weeks in culture, indicating the ability of the acellular brain sections to support sustained ex vivo growth of NSC. Next, the organization of a 3D maze-like cellular structure was examined using confocal microscopy. Moreover, under mitogenic stimuli (EGF and hFGF-2), most cells in this 3D culture retained their NSC phenotype. Concluding, we here present a novel protocol for decellularization of mouse brain sections, which subsequently support long-term 3D culture of undifferentiated NSC.

  3. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    PubMed

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  4. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome.

    PubMed

    De Felice, Claudio; Della Ragione, Floriana; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Ciccoli, Lucia; Scalabrì, Francesco; Marracino, Federico; Madonna, Michele; Belmonte, Giuseppe; Ricceri, Laura; De Filippis, Bianca; Laviola, Giovanni; Valacchi, Giuseppe; Durand, Thierry; Galano, Jean-Marie; Oger, Camille; Guy, Alexandre; Bultel-Poncé, Valérie; Guy, Jacky; Filosa, Stefania; Hayek, Joussef; D'Esposito, Maurizio

    2014-08-01

    Rett syndrome (RTT) is a rare neurodevelopmental disorder affecting almost exclusively females, caused in the overwhelming majority of the cases by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2). High circulating levels of oxidative stress (OS) markers in patients suggest the involvement of OS in the RTT pathogenesis. To investigate the occurrence of oxidative brain damage in Mecp2 mutant mouse models, several OS markers were evaluated in whole brains of Mecp2-null (pre-symptomatic, symptomatic, and rescued) and Mecp2-308 mutated (pre-symptomatic and symptomatic) mice, and compared to those of wild type littermates. Selected OS markers included non-protein-bound iron, isoprostanes (F2-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes) and 4-hydroxy-2-nonenal protein adducts. Our findings indicate that oxidative brain damage 1) occurs in both Mecp2-null (both -/y and stop/y) and Mecp2-308 (both 308/y males and 308/+ females) mouse models of RTT; 2) precedes the onset of symptoms in both Mecp2-null and Mecp2-308 models; and 3) is rescued by Mecp2 brain specific gene reactivation. Our data provide direct evidence of the link between Mecp2 deficiency, oxidative stress and RTT pathology, as demonstrated by the rescue of the brain oxidative homeostasis following brain-specifically Mecp2-reactivated mice. The present study indicates that oxidative brain damage is a previously unrecognized hallmark feature of murine RTT, and suggests that Mecp2 is involved in the protection of the brain from oxidative stress.

  5. 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…

  6. Stem Cell-Mediated Regeneration of the Adult Brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury of the adult mammalian brain is often associated with persistent functional deficits as its potential for regeneration and capacity to rebuild lost neural structures is limited. However, the discovery that neural stem cells (NSCs) persist throughout life in discrete regions of the brain, novel approaches to induce the formation of neuronal and glial cells, and recently developed strategies to generate tissue for exogenous cell replacement strategies opened novel perspectives how to regenerate the adult brain. Here, we will review recently developed approaches for brain repair and discuss future perspectives that may eventually allow for developing novel treatment strategies in acute and chronic brain injury. PMID:27781019

  7. Triangulating the sexually dimorphic brain through high-resolution neuroimaging of murine sex chromosome aneuploidies

    PubMed Central

    Lue, YanHe; Probst, Frank; Greenstein, Deanna; Giedd, Jay; Wang, Christina; Lerch, Jason; Swerdloff, Ronald

    2016-01-01

    Murine sex chromosome aneuploidies (SCAs) provide powerful models for charting sex chromosome influences on mammalian brain development. Here, building on prior work in X-monosomic (XO) mice, we use spatially non-biased high-resolution imaging to compare and contrast neuroanatomical alterations in XXY and XO mice relative to their wild-type XX and XY littermates. First, we show that carriage of a supernumerary X chromosome in XXY males (1) does not prevent normative volumetric masculinization of the bed nucleus of the stria terminalis (BNST) and medial amygdala, but (2) causes distributed anatomical alterations relative to XY males, which show a statistically unexpected tendency to be colocalized with and reciprocal to XO-XX differences in anatomy. These overlaps identify the lateral septum, BNST, ventral group thalamic nuclei and periaqueductal gray matter as regions with replicable sensitivity to X chromosome dose across two SCAs. We then harness anatomical variation across all four karyotype groups in our study—XO, XX, XY and XXY—to create an agnostic data-driven segmentation of the mouse brain into five distributed clusters which (1) recover fundamental properties of brain organization with high spatial precision, (2) define two previously uncharacterized systems of relative volume excess in females vs. males (“forebrain cholinergic” and “cerebelo-pontine-thalamo-cortical”), and (3) adopt stereotyped spatial motifs which delineate ordered gradients of sex chromosome and gonadal influences on volumetric brain development. Taken together, these data provide a new framework for the study of sexually dimorphic influences on brain development in health and disrupted brain development in SCA. PMID:25146308

  8. Triangulating the sexually dimorphic brain through high-resolution neuroimaging of murine sex chromosome aneuploidies.

    PubMed

    Raznahan, Armin; Lue, YanHe; Probst, Frank; Greenstein, Deanna; Giedd, Jay; Wang, Christina; Lerch, Jason; Swerdloff, Ronald

    2015-11-01

    Murine sex chromosome aneuploidies (SCAs) provide powerful models for charting sex chromosome influences on mammalian brain development. Here, building on prior work in X-monosomic (XO) mice, we use spatially non-biased high-resolution imaging to compare and contrast neuroanatomical alterations in XXY and XO mice relative to their wild-type XX and XY littermates. First, we show that carriage of a supernumerary X chromosome in XXY males (1) does not prevent normative volumetric masculinization of the bed nucleus of the stria terminalis (BNST) and medial amygdala, but (2) causes distributed anatomical alterations relative to XY males, which show a statistically unexpected tendency to be co-localized with and reciprocal to XO-XX differences in anatomy. These overlaps identify the lateral septum, BNST, ventral group thalamic nuclei and periaqueductal gray matter as regions with replicable sensitivity to X chromosome dose across two SCAs. We then harness anatomical variation across all four karyotype groups in our study--XO, XX, XY and XXY--to create an agnostic data-driven segmentation of the mouse brain into five distributed clusters which (1) recover fundamental properties of brain organization with high spatial precision, (2) define two previously uncharacterized systems of relative volume excess in females vs. males ("forebrain cholinergic" and "cerebelo-pontine-thalamo-cortical"), and (3) adopt stereotyped spatial motifs which delineate ordered gradients of sex chromosome and gonadal influences on volumetric brain development. Taken together, these data provide a new framework for the study of sexually dimorphic influences on brain development in health and disrupted brain development in SCA.

  9. Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors

    PubMed Central

    Parker, Jacqueline N.; Gillespie, G. Yancey; Love, Cammy E.; Randall, Suzanne; Whitley, Richard J.; Markert, James M.

    2000-01-01

    Genetically engineered, neuroattenuated herpes simplex viruses (HSVs) expressing various cytokines can improve survival when used in the treatment of experimental brain tumors. These attenuated viruses have both copies of γ134.5 deleted. Recently, we demonstrated increased survival of C57BL/6 mice bearing syngeneic GL-261 gliomas when treated with an engineered HSV expressing IL-4, as compared with treatment with the parent construct (γ134.5−) alone or with a virus expressing IL-10. Herein, we report construction of a conditionally replication-competent mutant expressing both subunits of mIL-12 (M002) and its evaluation in a syngeneic neuroblastoma murine model. IL-12 induces a helper T cell subset type 1 response, which may induce more durable antitumor effects. In vitro studies showed that, when infected with M002, both Vero cells and murine Neuro-2a neuroblastoma cells produced physiologically relevant levels of IL-12 heterodimers, as determined by ELISA. M002 was cytotoxic for Neuro-2a cells and human glioma cell lines U251MG and D54MG. Neurotoxicity studies, as defined by plaque-forming units/LD50, performed in HSV-1-sensitive A/J strain mice found that M002 was not toxic even at high doses. When evaluated in an intracranial syngeneic neuroblastoma murine model, median survival of M002-treated animals was significantly longer than the median survival of animals treated with R3659, the parent γ134.5− mutant lacking any cytokine gene insert. Immunohistochemical analysis of M002-treated tumors identified a pronounced influx of CD4+ T cells and macrophages as well as CD8+ cells when compared with an analysis of R3659-treated tumors. We conclude that M002 produced a survival benefit via oncolytic effects combined with immunologic effects meditated by helper T cells of subset type 1. PMID:10681459

  10. Dendritic development of newly generated neurons in the adult brain.

    PubMed

    Ribak, Charles E; Shapiro, Lee A

    2007-10-01

    Ramon y Cajal described the fundamental morphology of the dendritic and axonal growth cones of neurons during development. However, technical limitations at the time prevented him from describing such growth cones from newborn neurons in the adult brain. The phenomenon of adult neurogenesis is briefly reviewed, and the structural description of dendritic and axonal outgrowth for these newly generated neurons in the adult brain is discussed. Axonal outgrowth into the hilus and CA3 region of the hippocampus occurs later than the outgrowth of dendrites into the molecular layer, and the ultrastructural analysis of axonal outgrowth has yet to be completed. In contrast, growth cones on dendrites from newborn neurons in the adult dentate gyrus have been described and this observation suggests that dendrites in adult brains grow in a similar way to those found in immature brains. However, dendrites in adult brains have to navigate through a denser neuropil and a more complex cell layer. Therefore, some aspects of dendritic outgrowth of neurons born in the adult dentate gyrus are different as compared to that found in development. These differences include the radial process of radial glial cells acting as a lattice to guide apical dendritic growth through the granule cell layer and a much thinner dendrite to grow through the neuropil of the molecular layer. Therefore, similarities and differences exist for dendritic outgrowth from newborn neurons in the developing and adult brain.

  11. Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains.

    PubMed

    de Haan, J B; Newman, J D; Kola, I

    1992-04-01

    To protect against reactive oxygen species, prokaryotic and eukaryotic cells have developed an antioxidant defence mechanism where O2- is converted to H2O2 by superoxide dismutase (Sod), and in a second step, H2O2 is converted to H2O by catalase (Cat) and/or glutathione peroxidase (Gpx). If Sod levels are increased without a concomitant Gpx increase, then the intermediate H2O2 accumulates. This intermediate could undergo the Fenton's reaction, generating hydroxyl radicals which may lead to lipid peroxidation in cells. In this study, we investigate the expression of Sod1, Gpx1 and susceptibility to lipid peroxidation during the aging process in mouse brains. We demonstrate that the mRNA levels and enzyme activity of Sod1 are higher in brains from adult mice compared to neonatal mice. Furthermore, we show that a linear increase in Sod1 mRNA and enzyme activity occurs with aging (1-100 weeks). On the contrary, we find that the mRNA and enzyme activity for Gpx1 does not increase with aging in mouse brains. In addition, our results demonstrate that the susceptibility of murine brains to lipid peroxidation increases with aging. The data in this study are consistent with the notion that reactive oxygen species may contribute to the aging process in mammalian brains. These results are discussed in relation to the normal aging process in mammals, and to the premature aging and mental retardation in Down syndrome.

  12. 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 ...

  13. Cloning and expression of a murine fascin homolog from mouse brain.

    PubMed

    Edwards, R A; Herrera-Sosa, H; Otto, J; Bryan, J

    1995-05-01

    The fascins are a widely distributed family of proteins that organize filamentous actin into bundles. We have cloned, sequenced, and expressed the murine homolog. Fascin is most abundant in brain and is found in other tissues including uterus and spleen. The deduced open reading frame encodes a protein of 493 amino acids with a molecular mass of 54,412 Da. Previous solubility problems with bacterially expressed fascins were overcome by producing the mouse protein as a fusion with Escherichia coli thioredoxin. A method for cleaving the fusion protein and for purifying active recombinant fascin is described. The N-terminal sequence and molecular mass estimated on SDS gels indicate that recombinant fascin is full-length. Two-dimensional gel electrophoresis suggests that recombinant fascin is post-translationally modified in a manner similar to that observed in mouse brain. Recombinant fascin and the fusion protein are recognized by monoclonal anti-fascin antibodies and will bundle rabbit skeletal muscle F-actin in vitro at a stoichiometry of 4.1:1 actin to fascin. Electron cryomicroscopy images show that the reconstituted bundles are highly ordered. However, their fine structure differs from that of echinoid fascin-actin bundles. This structural difference can be attributed to fascin.

  14. Critical care management of severe traumatic brain injury in adults

    PubMed Central

    2012-01-01

    Traumatic brain injury (TBI) is a major medical and socio-economic problem, and is the leading cause of death in children and young adults. The critical care management of severe TBI is largely derived from the "Guidelines for the Management of Severe Traumatic Brain Injury" that have been published by the Brain Trauma Foundation. The main objectives are prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure (CPP), and optimization of cerebral oxygenation. In this review, the critical care management of severe TBI will be discussed with focus on monitoring, avoidance and minimization of secondary brain insults, and optimization of cerebral oxygenation and CPP. PMID:22304785

  15. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

    PubMed Central

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

  16. Cell proliferation and neurogenesis in adult mouse brain.

    PubMed

    Bordiuk, Olivia L; Smith, Karen; Morin, Peter J; Semënov, Mikhail V

    2014-01-01

    Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU) to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ), and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS) occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain.

  17. Cell proliferation and neurogenesis in adult mouse brain.

    PubMed

    Bordiuk, Olivia L; Smith, Karen; Morin, Peter J; Semënov, Mikhail V

    2014-01-01

    Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU) to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ), and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS) occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain. PMID:25375658

  18. Sociosexual and Communication Deficits after Traumatic Injury to the Developing Murine Brain

    PubMed Central

    Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Jun Kwon, Yong; Sam, Pingdewinde N.; Gibson, A. Matt; Grissom, Sarah; Brown, Sienna; Adahman, Zahra; Hollingsworth, Christopher A.; Kwakye, Alexander; Gimlin, Kayleen; Wilde, Elisabeth A.; Hanten, Gerri; Levin, Harvey S.; Schenk, A. Katrin

    2014-01-01

    Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21) or during adolescence (p35). Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs) as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35

  19. Sociosexual and communication deficits after traumatic injury to the developing murine brain.

    PubMed

    Semple, Bridgette D; Noble-Haeusslein, Linda J; Jun Kwon, Yong; Sam, Pingdewinde N; Gibson, A Matt; Grissom, Sarah; Brown, Sienna; Adahman, Zahra; Hollingsworth, Christopher A; Kwakye, Alexander; Gimlin, Kayleen; Wilde, Elisabeth A; Hanten, Gerri; Levin, Harvey S; Schenk, A Katrin

    2014-01-01

    Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21) or during adolescence (p35). Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs) as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35

  20. 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…

  1. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    SciTech Connect

    Weinberger, Florian Mehrkens, Dennis Starbatty, Jutta Nicol, Philipp Eschenhagen, Thomas

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  2. Partial Characterization of the Sox2+ Cell Population in an Adult Murine Model of Digit Amputation

    PubMed Central

    Agrawal, Vineet; Siu, Bernard F.; Chao, Hsu; Hirschi, Karen K.; Raborn, Eric; Johnson, Scott A.; Tottey, Stephen; Hurley, Katherine B.; Medberry, Chris J.

    2012-01-01

    Tissue regeneration in response to injury in adult mammals is generally limited to select tissues. Nonmammalian species such as newts and axolotls undergo regeneration of complex tissues such as limbs and digits via recruitment and accumulation of local and circulating multipotent progenitors preprogrammed to recapitulate the missing tissue. Directed recruitment and activation of progenitor cells at a site of injury in adult mammals may alter the default wound-healing response from scar tissue toward regeneration. Bioactive molecules derived from proteolytic degradation of extracellular matrix (ECM) proteins have been shown to recruit a variety of progenitor cells in vitro and in vivo to the site of injury. The present study further characterized the population of cells accumulating at the site of injury after treatment with ECM degradation products in a well-established model of murine digit amputation. After a mid-second phalanx digit amputation in 6–8-week-old adult mice, treatment with ECM degradation products resulted in the accumulation of a heterogeneous population of cells, a subset of which expressed the transcription factor Sox2, a marker of pluripotent and adult progenitor cells. Sox2+ cells were localized lateral to the amputated P2 bone and coexpressed progenitor cell markers CD90 and Sca1. Transgenic Sox2 eGFP/+ and bone marrow chimeric mice showed that the bone marrow and blood circulation did not contribute to the Sox2+ cell population. The present study showed that, in addition to circulating progenitor cells, resident tissue-derived cells also populate at the site of injury after treatment with ECM degradation products. Although future work is necessary to determine the contribution of Sox2+ cells to functional tissue at the site of injury, recruitment and/or activation of local tissue-derived cells may be a viable approach to tissue engineering of more complex tissues in adult mammals. PMID:22530556

  3. Label-Retaining Cells in the Adult Murine Salivary Glands Possess Characteristics of Adult Progenitor Cells

    PubMed Central

    Chibly, Alejandro M.; Querin, Lauren; Harris, Zoey; Limesand, Kirsten H.

    2014-01-01

    Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2′-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction. PMID:25238060

  4. Label-retaining cells in the adult murine salivary glands possess characteristics of adult progenitor cells.

    PubMed

    Chibly, Alejandro M; Querin, Lauren; Harris, Zoey; Limesand, Kirsten H

    2014-01-01

    Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2'-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction.

  5. 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…

  6. Neural stem cells in the adult human brain

    PubMed Central

    Gonzalez-Perez, Oscar

    2012-01-01

    For decades, it was believed that the adult brain was a quiescent organ unable to produce new neurons. At the beginning of the1960's, this dogma was challenged by a small group of neuroscientists. To date, it is well-known that new neurons are generated in the adult brain throughout life. Adult neurogenesis is primary confined to the subventricular zone (SVZ) of the forebrain and the subgranular zone of the dentate gyrus within the hippocampus. In both the human and the rodent brain, the primary progenitor of adult SVZ is a subpopulation of astrocytes that have stem-cell-like features. The human SVZ possesses a peculiar cell composition and displays important organizational differences when compared to the SVZ of other mammals. Some evidence suggests that the human SVZ may be not only an endogenous source of neural precursor cells for brain repair, but also a source of brain tumors. In this review, we described the cytoarchitecture and cellular composition of the SVZ in the adult human brain. We also discussed some clinical implications of SVZ, such as: stem-cell-based therapies against neurodegenerative diseases and its potential as a source of malignant cells. Understanding the biology of human SVZ and its neural progenitors is one of the crucial steps to develop novel therapies against neurological diseases in humans. PMID:23181200

  7. 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.

  8. 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)

  9. [Generation of new nerve cells in the adult human brain].

    PubMed

    Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

    2003-03-31

    Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known whether neurogenesis in the adult human brain can be manipulated for specific repair after brain damage.

  10. Identification and enrichment of colony-forming cells from the adult murine pituitary

    SciTech Connect

    Lepore, D.A.; Roeszler, K.; Wagner, J.; Ross, S.A.; Bauer, K.; Thomas, P.Q. , E-Mail: paul.thomas@mcri.edu.au

    2005-08-01

    Stem and progenitor cells have been identified in many adult tissues including bone marrow, the central nervous system, and skin. While there is direct evidence to indicate the activity of a progenitor cell population in the pituitary gland, this putative subpopulation has not yet been identified. Herein we describe the isolation and characterization of a novel clonogenic cell type in the adult murine pituitary, which we have termed Pituitary Colony-Forming Cells (PCFCs). PCFCs constitute 0.2% of pituitary cells, and generate heterogeneous colonies from single cells. PCFCs exhibit variable proliferative potential, and may exceed 11 population doublings in 14 days. Enrichment of PCFCs to 61.5-fold with 100% recovery can be obtained through the active uptake of the fluorescent dipeptide, {beta}-Ala-Lys-N{epsilon}-AMCA. PCFCs are mostly contained within the large, agranular subpopulation of AMCA{sup +} cells, and constitute 28% of this fraction, corresponding to 140.5-fold enrichment. Interestingly, the AMCA{sup +} population contains rare cells that are GH{sup +} or PRL{sup +}. GH{sup +} cells were also identified in PCFC single cell colonies, suggesting that PCFCs have the potential to differentiate into GH{sup +} cells. Together, these data show that the pituitary contains a rare clonogenic population which may correspond to the somatotrope/lactotrope progenitors suggested by previous experiments.

  11. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  12. Treatment with tetrahydrobiopterin overcomes brain death-associated injury in a murine model of pancreas transplantation.

    PubMed

    Oberhuber, R; Ritschl, P; Fabritius, C; Nguyen, A-V; Hermann, M; Obrist, P; Werner, E R; Maglione, M; Flörchinger, B; Ebner, S; Resch, T; Pratschke, J; Kotsch, K

    2015-11-01

    Brain death (BD) has been associated with an immunological priming of donor organs and is thought to exacerbate ischemia reperfusion injury (IRI). Recently, we showed that the essential nitric oxide synthase co-factor tetrahydrobiopterin (BH4) abrogates IRI following experimental pancreas transplantation. We therefore studied the effects of BD in a murine model of syngeneic pancreas transplantation and tested the therapeutic potential of BH4 treatment. Compared with sham-operated controls, donor BD resulted in intragraft inflammation reflected by induced IL-1ß, IL-6, VCAM-1, and P-selectin mRNA expression levels and impaired microcirculation after reperfusion (p < 0.05), whereas pretreatment of the BD donor with BH4 significantly improved microcirculation after reperfusion (p < 0.05). Moreover, BD had a devastating impact on cell viability, whereas BH4-treated grafts showed a significantly higher percentage of viable cells (p < 0.001). Early parenchymal damage in pancreatic grafts was significantly more pronounced in organs from BD donors than from sham or non-BD donors (p < 0.05), but BH4 pretreatment significantly ameliorated necrotic lesions in BD organs (p < 0.05). Pretreatment of the BD donor with BH4 resulted in significant recipient survival (p < 0.05). Our data provide novel insights into the impact of BD on pancreatic isografts, further demonstrating the potential of donor pretreatment strategies including BH4 for preventing BD-associated injury after transplantation.

  13. A longitudinal magnetic resonance elastography study of murine brain tumors following radiation therapy

    NASA Astrophysics Data System (ADS)

    Feng, Y.; Clayton, E. H.; Okamoto, R. J.; Engelbach, J.; Bayly, P. V.; Garbow, J. R.

    2016-08-01

    An accurate and noninvasive method for assessing treatment response following radiotherapy is needed for both treatment monitoring and planning. Measurement of solid tumor volume alone is not sufficient for reliable early detection of therapeutic response, since changes in physiological and/or biomechanical properties can precede tumor volume change following therapy. In this study, we use magnetic resonance elastography to evaluate the treatment effect after radiotherapy in a murine brain tumor model. Shear modulus was calculated and compared between the delineated tumor region of interest (ROI) and its contralateral, mirrored counterpart. We also compared the shear modulus from both the irradiated and non-irradiated tumor and mirror ROIs longitudinally, sampling four time points spanning 9–19 d post tumor implant. Results showed that the tumor ROI had a lower shear modulus than that of the mirror ROI, independent of radiation. The shear modulus of the tumor ROI decreased over time for both the treated and untreated groups. By contrast, the shear modulus of the mirror ROI appeared to be relatively constant for the treated group, while an increasing trend was observed for the untreated group. The results provide insights into the tumor properties after radiation treatment and demonstrate the potential of using the mechanical properties of the tumor as a biomarker. In future studies, more closely spaced time points will be employed for detailed analysis of the radiation effect.

  14. A longitudinal magnetic resonance elastography study of murine brain tumors following radiation therapy

    NASA Astrophysics Data System (ADS)

    Feng, Y.; Clayton, E. H.; Okamoto, R. J.; Engelbach, J.; Bayly, P. V.; Garbow, J. R.

    2016-08-01

    An accurate and noninvasive method for assessing treatment response following radiotherapy is needed for both treatment monitoring and planning. Measurement of solid tumor volume alone is not sufficient for reliable early detection of therapeutic response, since changes in physiological and/or biomechanical properties can precede tumor volume change following therapy. In this study, we use magnetic resonance elastography to evaluate the treatment effect after radiotherapy in a murine brain tumor model. Shear modulus was calculated and compared between the delineated tumor region of interest (ROI) and its contralateral, mirrored counterpart. We also compared the shear modulus from both the irradiated and non-irradiated tumor and mirror ROIs longitudinally, sampling four time points spanning 9-19 d post tumor implant. Results showed that the tumor ROI had a lower shear modulus than that of the mirror ROI, independent of radiation. The shear modulus of the tumor ROI decreased over time for both the treated and untreated groups. By contrast, the shear modulus of the mirror ROI appeared to be relatively constant for the treated group, while an increasing trend was observed for the untreated group. The results provide insights into the tumor properties after radiation treatment and demonstrate the potential of using the mechanical properties of the tumor as a biomarker. In future studies, more closely spaced time points will be employed for detailed analysis of the radiation effect.

  15. Characterization of Murine Brain Membrane Glycoproteins by Detergent Assisted Lectin Affinity Chromatography (DALAC)

    PubMed Central

    Wei, Xin; Dulberger, Charles; Li, Lingjun

    2010-01-01

    Membrane glycoproteins play vital roles in many fundamental physiological and pathophysiological processes in the central nervous system and represent important targets for pharmaceuticals and biomarker discovery. However, their isolation and characterization has been greatly limited. Lectin affinity chromatography (LAC) has evolved as a powerful method to enrich glycoproteins in biofluid and cell/tissue lysate. However, its use in the hydrophobic fraction of the samples has rarely been explored. In this study, we have conducted a systematic investigation on the lectin binding efficiency in the presence of four commonly used detergents. We have found that under certain concentrations, detergents can minimize the nonspecific bindings and facilitate the elution of hydrophobic glycoproteins. With the Detergent Assisted Lectin Affinity Chromatography (DALAC), a total of 1491 proteins were identified with low numbers of false positives from two lectins. 699 proteins were identified with at least two unique peptides, of which 219 are membrane glycoproteins. Compared to the traditional methods, the DALAC approach significantly increased the recovery of plasma membrane and glycoproteins. NP-40 is recommended as a well rounded detergent for DALAC, but the conditions for enriching certain target proteins need to be empirically determined. This study represents the first global identification of the murine brain glycoproteome. PMID:20700909

  16. Nonessential Role for the NLRP1 Inflammasome Complex in a Murine Model of Traumatic Brain Injury

    PubMed Central

    Brickler, Thomas; Gresham, Kisha; Meza, Armand; Coutermarsh-Ott, Sheryl; Williams, Tere M.; Rothschild, Daniel E.; Allen, Irving C.; Theus, Michelle H.

    2016-01-01

    Traumatic brain injury (TBI) elicits the immediate production of proinflammatory cytokines which participate in regulating the immune response. While the mechanisms of adaptive immunity in secondary injury are well characterized, the role of the innate response is unclear. Recently, the NLR inflammasome has been shown to become activated following TBI, causing processing and release of interleukin-1β (IL-1β). The inflammasome is a multiprotein complex consisting of nucleotide-binding domain and leucine-rich repeat containing proteins (NLR), caspase-1, and apoptosis-associated speck-like protein (ASC). ASC is upregulated after TBI and is critical in coupling the proteins during complex formation resulting in IL-1β cleavage. To directly test whether inflammasome activation contributes to acute TBI-induced damage, we assessed IL-1β, IL-18, and IL-6 expression, contusion volume, hippocampal cell death, and motor behavior recovery in Nlrp1−/−, Asc−/−, and wild type mice after moderate controlled cortical impact (CCI) injury. Although IL-1β expression is significantly attenuated in the cortex of Nlrp1−/− and Asc−/− mice following CCI injury, no difference in motor recovery, cell death, or contusion volume is observed compared to wild type. These findings indicate that inflammasome activation does not significantly contribute to acute neural injury in the murine model of moderate CCI injury. PMID:27199506

  17. 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

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

    PubMed

    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

    2005-07-19

    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).

  19. Angiopoietin 2 stimulates migration and tube-like structure formation of murine brain capillary endothelial cells through c-Fes and c-Fyn.

    PubMed

    Mochizuki, Yasushi; Nakamura, Takao; Kanetake, Hiroshi; Kanda, Shigeru

    2002-01-01

    The angiopoietin (Ang)/Tie2 system is exclusively involved in vasculogenesis and angiogenesis. Ang2 is known to inhibit Ang1-mediated phosphorylation of Tie2 as well as cellular responses during embryonic development. Recent studies have demonstrated that Ang2 has angiogenic activities in adult tissues and cultured endothelial cells. In the present study, we examined the downstream signaling pathways involved in Ang2-mediated cellular responses by murine brain capillary cell line, IBE cells. Tie2 was tyrosine phoshorylated by Ang2. Ang2 showed no effect on proliferation, but stimulated chemotaxis and tube-like structure formation. Phosphoinositide 3-kinase (PI 3-kinase) was activated by Ang2 through c-Fes and was involved in chemotaxis toward Ang2. Ang2 also activated c-Fyn in IBE cells. Cells expressing kinase-inactive c-Fyn attenuated Ang2-induced tube formation, suggesting that c-Fyn was responsible for Ang-2-mediated tube formation. Collecting these data, Ang2 activates c-Fes and c-Fyn, leading to migration and tube formation by murine capillary endothelial cells.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. Brain abscess caused by Citrobacter koseri infection in an adult.

    PubMed

    Liu, Heng-Wei; Chang, Chih-Ju; Hsieh, Cheng-Ta

    2015-04-01

    Citrobacter koseri is a gram-negative bacillus that causes mostly meningitis and brain abscesses in neonates and infants. However, brain abscess caused by Citrobacter koseri infection in an adult is extremely rare, and only 2 cases have been described. Here, we reported a 73-year-old male presenting with a 3-week headache. A history of diabetes mellitus was noted. The images revealed a brain abscess in the left frontal lobe and pus culture confirmed the growth of Citrobacter koseri. The clinical symptoms improved completely postoperatively.

  5. Transcriptomic Analysis of the Effects of a Fish Oil Enriched Diet on Murine Brains

    PubMed Central

    Gautam, Aarti; Miller, Stacy-Ann; Muhie, Seid; Meyerhoff, James; Jett, Marti

    2014-01-01

    The health benefits of fish oil enriched with high omega-3 polyunsaturated fatty acids (n-3 PUFA) are widely documented. Fish oil as dietary supplements, however, show moderate clinical efficacy, highlighting an immediate scope of systematic in vitro feedback. Our transcriptomic study was designed to investigate the genomic shift of murine brains fed on fish oil enriched diets. A customized fish oil enriched diet (FD) and standard lab diet (SD) were separately administered to two randomly chosen populations of C57BL/6J mice from their weaning age until late adolescence. Statistical analysis mined 1,142 genes of interest (GOI) differentially altered in the hemibrains collected from the FD- and SD-fed mice at the age of five months. The majority of identified GOI (∼40%) encodes proteins located in the plasma membrane, suggesting that fish oil primarily facilitated the membrane-oriented biofunctions. FD potentially augmented the nervous system's development and functions by selectively stimulating the Src-mediated calcium-induced growth cascade and the downstream PI3K-AKT-PKC pathways. FD reduced the amyloidal burden, attenuated oxidative stress, and assisted in somatostatin activation—the signatures of attenuation of Alzheimer's disease, Parkinson's disease, and affective disorder. FD induced elevation of FKBP5 and suppression of BDNF, which are often linked with the improvement of anxiety disorder, depression, and post-traumatic stress disorder. Hence we anticipate efficacy of FD in treating illnesses such as depression that are typically triggered by the hypoactivities of dopaminergic, adrenergic, cholinergic, and GABAergic networks. Contrastingly, FD's efficacy could be compromised in treating illnesses such as bipolar disorder and schizophrenia, which are triggered by hyperactivities of the same set of neuromodulators. A more comprehensive investigation is recommended to elucidate the implications of fish oil on disease pathomechanisms, and the result

  6. Transcriptomic analysis of the effects of a fish oil enriched diet on murine brains.

    PubMed

    Hammamieh, Rasha; Chakraborty, Nabarun; Gautam, Aarti; Miller, Stacy-Ann; Muhie, Seid; Meyerhoff, James; Jett, Marti

    2014-01-01

    The health benefits of fish oil enriched with high omega-3 polyunsaturated fatty acids (n-3 PUFA) are widely documented. Fish oil as dietary supplements, however, show moderate clinical efficacy, highlighting an immediate scope of systematic in vitro feedback. Our transcriptomic study was designed to investigate the genomic shift of murine brains fed on fish oil enriched diets. A customized fish oil enriched diet (FD) and standard lab diet (SD) were separately administered to two randomly chosen populations of C57BL/6J mice from their weaning age until late adolescence. Statistical analysis mined 1,142 genes of interest (GOI) differentially altered in the hemibrains collected from the FD- and SD-fed mice at the age of five months. The majority of identified GOI (∼ 40%) encodes proteins located in the plasma membrane, suggesting that fish oil primarily facilitated the membrane-oriented biofunctions. FD potentially augmented the nervous system's development and functions by selectively stimulating the Src-mediated calcium-induced growth cascade and the downstream PI3K-AKT-PKC pathways. FD reduced the amyloidal burden, attenuated oxidative stress, and assisted in somatostatin activation-the signatures of attenuation of Alzheimer's disease, Parkinson's disease, and affective disorder. FD induced elevation of FKBP5 and suppression of BDNF, which are often linked with the improvement of anxiety disorder, depression, and post-traumatic stress disorder. Hence we anticipate efficacy of FD in treating illnesses such as depression that are typically triggered by the hypoactivities of dopaminergic, adrenergic, cholinergic, and GABAergic networks. Contrastingly, FD's efficacy could be compromised in treating illnesses such as bipolar disorder and schizophrenia, which are triggered by hyperactivities of the same set of neuromodulators. A more comprehensive investigation is recommended to elucidate the implications of fish oil on disease pathomechanisms, and the result

  7. Abnormal brain structure in adults with Van der Woude syndrome.

    PubMed

    Nopoulos, P; Richman, L; Andreasen, N C; Murray, J C; Schutte, B

    2007-06-01

    Van der Woude syndrome (VWS) is an autosomal dominant disorder manifested in cleft lip and/or palate and lip pits. Isolated clefts of the lip and/or palate (ICLP) have both genotype and phenotype overlap with VWS. Subjects with ICLP have abnormalities in brain structure and function. Given the similarities between VWS and ICLP, the current study was designed to evaluate the pattern of brain structure of adults with VWS. Fourteen adults with VWS were compared to age- and gender-matched healthy controls. Brain structure was evaluated using magnetic resonance imaging. All subjects with VWS had enlarged volumes of the anterior regions of the cerebrum. Men with VWS had reduced volumes of the posterior cerebrum. Anterior cerebrum volume was negatively correlated with intelligent quotient in the subjects with VWS indicating that the enlargement of this brain region was 'pathologic.' The pattern of brain structure in VWS is nearly identical to those seen in ICLP. In addition, men are affected more severely. Pathologic enlargement of the tissue and a gender effect with men affected more severely are common features of neurodevelopmental disorders supporting the notion that the brain structure of VWS and ICLP may be because of abnormal brain development. PMID:17539900

  8. Narrative Skills Following Traumatic Brain Injury in Children and Adults.

    ERIC Educational Resources Information Center

    Biddle, Kathleen R.; And Others

    1996-01-01

    This study used dependency analysis to document and describe the narrative discourse impairments of 10 children (mean age 12) and 10 adults (mean age 35) with traumatic brain injury (TBI), and matched controls. Individuals with TBI were significantly more disfluent than controls and their narrative performance required a significant listener…

  9. 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,…

  10. 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

  11. 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

  12. [Endocrine functions of the brain in adult and developing mammals].

    PubMed

    Ugriumov, M V

    2009-01-01

    The main prerequisite for organism's viability is the maintenance of the internal environment despite changes in the external environment, which is provided by the neuroendocrine control system. The key unit in this system is hypothalamus exerting endocrine effects on certain peripheral organs and anterior pituitary. Physiologically active substances of neuronal origin enter blood vessels in the neurohemal parts of hypothalamus where no blood-brain barrier exists. In other parts of the adult brain, the arrival of physiologically active substances is blocked by the blood-brain barrier. According to the generally accepted concept, the neuroendocrine system formation in ontogeny starts with the maturation of peripheral endocrine glands, which initially function autonomously and then are controlled by the anterior pituitary. The brain is engaged in neuroendocrine control after its maturation completes, which results in a closed control system typical of adult mammals. Since neurons start to secrete physiologically active substances soon after their formation and long before interneuronal connections are formed, these cells are thought to have an effect on brain development as inducers. Considering that there is no blood-brain barrier during this period, we proposed the hypothesis that the developing brain functions as a multipotent endocrine organ. This means that tens of physiologically active substances arrive from the brain to the systemic circulation and have an endocrine effect on the whole body development. Dopamine, serotonin, and gonadotropin-releasing hormone were selected as marker physiologically active substances of cerebral origin to test this hypothesis. In adult animals, they act as neurotransmitters or neuromodulators transmitting information from neuron to neuron as well as neurohormones arriving from the hypothalamus with portal blood to the anterior pituitary. Perinatal rats--before the blood-brain barrier is formed--proved to have equally high

  13. Relationships between Gene Expression and Brain Wiring in the Adult Rodent Brain

    PubMed Central

    French, Leon; Pavlidis, Paul

    2011-01-01

    We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain “connectome” from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS. PMID:21253556

  14. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

    PubMed Central

    Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.

    2010-01-01

    SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844

  15. Life satisfaction in adult survivors of childhood brain tumors.

    PubMed

    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, lifelong 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 suggest 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 that 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.

  16. 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.

  17. Persistent Representation of Juvenile Experience in the Adult Songbird Brain

    PubMed Central

    Prather, JF; Peters, S; Nowicki, S; Mooney, R

    2010-01-01

    Juveniles sometimes learn behaviors that they cease to express as adults. Whether the adult brain retains a record of experiences associated with behaviors performed transiently during development remains unclear. We addressed this issue by studying neural representations of song in swamp sparrows, a species in which juveniles learn and practice many more songs than they retain in their adult vocal repertoire. We exposed juvenile swamp sparrows to a suite of tutor songs and confirmed that although many tutor songs were imitated during development, not all copied songs were retained into adulthood. We then recorded extracellularly in the sensorimotor nucleus HVC in anesthetized sparrows to assess neuronal responsiveness to songs in the adult repertoire, tutor songs, and novel songs. Individual HVC neurons almost always responded to songs in the adult repertoire and commonly responded even more strongly to a tutor song. Effective tutor songs were not simply those that were acoustically similar to songs in the adult repertoire. Moreover, the strength of tutor song responses was unrelated to the number of times that the bird sang copies of those songs in juvenile or adult life. Notably, several neurons responded most strongly to a tutor song performed only rarely and transiently during juvenile life, or even to a tutor song for which we could find no evidence of ever having been copied. Thus, HVC neurons representing songs in the adult repertoire also appear to retain a lasting record of certain tutor songs, including those imitated only transiently. PMID:20686001

  18. The Proteome of Native Adult Müller Glial Cells From Murine Retina.

    PubMed

    Grosche, Antje; Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca; von Toerne, Christine; Merl-Pham, Juliane; Hauck, Stefanie M

    2016-02-01

    To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

  19. 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

  20. Prenatal Ethanol Exposure Increases Brain Cholesterol Content in Adult Rats

    PubMed Central

    Barceló-Coblijn, Gwendolyn; Wold, Loren E.; Ren, Jun; Murphy, Eric J.

    2013-01-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content is known to change in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43%, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total PUFA, in the n-3/n-6 ratio, and in the 22:6 n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of post-natal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats. PMID:23996454

  1. IR and Raman imaging of murine brains from control and ApoE/LDLR(-/-) mice with advanced atherosclerosis.

    PubMed

    Kochan, Kamila; Chrabaszcz, Karolina; Szczur, Barbara; Maslak, Edyta; Dybas, Jakub; Marzec, Katarzyna M

    2016-09-21

    Confocal Raman mapping and FT-IR imaging combined with chemometric analysis was used to study the alterations in murine brain tissue induced by the development of atherosclerosis. FT-IR imaging allowed us to obtain lower spatial resolution data (∼5.5 μm) from large, representative cross-sectional brain areas, while Raman mapping provided a more detailed insight into chosen regions of interest with high spatial resolution (∼0.4 μm). A comparison of white (WM) and grey matter (GM) from control (C57BL/6J) and ApoE/LDLR(-/-) mice with advanced atherosclerosis revealed disease-induced changes in both: GM and WM. The alterations included an increased lipid to protein ratio and higher total content of cholesterol.

  2. IR and Raman imaging of murine brains from control and ApoE/LDLR(-/-) mice with advanced atherosclerosis.

    PubMed

    Kochan, Kamila; Chrabaszcz, Karolina; Szczur, Barbara; Maslak, Edyta; Dybas, Jakub; Marzec, Katarzyna M

    2016-09-21

    Confocal Raman mapping and FT-IR imaging combined with chemometric analysis was used to study the alterations in murine brain tissue induced by the development of atherosclerosis. FT-IR imaging allowed us to obtain lower spatial resolution data (∼5.5 μm) from large, representative cross-sectional brain areas, while Raman mapping provided a more detailed insight into chosen regions of interest with high spatial resolution (∼0.4 μm). A comparison of white (WM) and grey matter (GM) from control (C57BL/6J) and ApoE/LDLR(-/-) mice with advanced atherosclerosis revealed disease-induced changes in both: GM and WM. The alterations included an increased lipid to protein ratio and higher total content of cholesterol. PMID:27332112

  3. 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.

  4. Clinical review: Brain-body temperature differences in adults with severe traumatic brain injury.

    PubMed

    Childs, Charmaine; Lunn, Kueh Wern

    2013-04-22

    Surrogate or 'proxy' measures of brain temperature are used in the routine management of patients with brain damage. The prevailing view is that the brain is 'hotter' than the body. The polarity and magnitude of temperature differences between brain and body, however, remains unclear after severe traumatic brain injury (TBI). The focus of this systematic review is on the adult patient admitted to intensive/neurocritical care with a diagnosis of severe TBI (Glasgow Coma Scale score of less than 8). The review considered studies that measured brain temperature and core body temperature. Articles published in English from the years 1980 to 2012 were searched in databases, CINAHL, PubMed, Scopus, Web of Science, Science Direct, Ovid SP, Mednar and ProQuest Dissertations & Theses Database. For the review, publications of randomised controlled trials, non-randomised controlled trials, before and after studies, cohort studies, case-control studies and descriptive studies were considered for inclusion. Of 2,391 records identified via the search strategies, 37 were retrieved for detailed examination (including two via hand searching). Fifteen were reviewed and assessed for methodological quality. Eleven studies were included in the systematic review providing 15 brain-core body temperature comparisons. The direction of mean brain-body temperature differences was positive (brain higher than body temperature) and negative (brain lower than body temperature). Hypothermia is associated with large brain-body temperature differences. Brain temperature cannot be predicted reliably from core body temperature. Concurrent monitoring of brain and body temperature is recommended in patients where risk of temperature-related neuronal damage is a cause for clinical concern and when deliberate induction of below-normal body temperature is instituted.

  5. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  6. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  7. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  8. Precise Anatomic Localization of Accumulated Lipids in Mfp2 Deficient Murine Brains Through Automated Registration of SIMS Images to the Allen Brain Atlas

    NASA Astrophysics Data System (ADS)

    Škrášková, Karolina; Khmelinskii, Artem; Abdelmoula, Walid M.; De Munter, Stephanie; Baes, Myriam; McDonnell, Liam; Dijkstra, Jouke; Heeren, Ron M. A.

    2015-06-01

    Mass spectrometry imaging (MSI) is a powerful tool for the molecular characterization of specific tissue regions. Histochemical staining provides anatomic information complementary to MSI data. The combination of both modalities has been proven to be beneficial. However, direct comparison of histology based and mass spectrometry-based molecular images can become problematic because of potential tissue damages or changes caused by different sample preparation. Curated atlases such as the Allen Brain Atlas (ABA) offer a collection of highly detailed and standardized anatomic information. Direct comparison of MSI brain data to the ABA allows for conclusions to be drawn on precise anatomic localization of the molecular signal. Here we applied secondary ion mass spectrometry imaging at high spatial resolution to study brains of knock-out mouse models with impaired peroxisomal β-oxidation. Murine models were lacking D-multifunctional protein (MFP2), which is involved in degradation of very long chain fatty acids. SIMS imaging revealed deposits of fatty acids within distinct brain regions. Manual comparison of the MSI data with the histologic stains did not allow for an unequivocal anatomic identification of the fatty acids rich regions. We further employed an automated pipeline for co-registration of the SIMS data to the ABA. The registration enabled precise anatomic annotation of the brain structures with the revealed lipid deposits. The precise anatomic localization allowed for a deeper insight into the pathology of Mfp2 deficient mouse models.

  9. Interaction of HM30181 with P-glycoprotein at the murine blood-brain barrier assessed with positron emission tomography

    PubMed Central

    Bauer, Florian; Wanek, Thomas; Mairinger, Severin; Stanek, Johann; Sauberer, Michael; Kuntner, Claudia; Parveen, Zahida; Chiba, Peter; Müller, Markus; Langer, Oliver; Erker, Thomas

    2013-01-01

    HM30181, a potent and selective inhibitor of the adenosine triphosphate-binding cassette transporter P-glycoprotein (Pgp), was shown to enhance oral bioavailability and improve antitumour efficacy of paclitaxel in mouse tumour models. In search for a positron emission tomography (PET) radiotracer to visualise Pgp expression levels at the blood-brain barrier (BBB), we examined the ability of HM30181 to inhibit Pgp at the murine BBB. HM30181 was shown to be approximately equipotent with the reference Pgp inhibitor tariquidar in inhibiting rhodamine 123 efflux from CCRF-CEM T cells (IC50, tariquidar: 8.2±2.0 nM, HM30181: 13.1±2.3 nM). PET scans with the Pgp substrate (R)-[11C]verapamil in FVB wild-type mice pretreated i.v. with HM30181 (10 or 21 mg/kg) failed to show significant increases in (R)-[11C]verapamil brain uptake compared with vehicle treated animals. PET scans with [11C]HM30181 showed low and not significantly different brain uptake of [11C]HM30181 in wild-type, Mdr1a/b(−/−) and Bcrp1(−/−) mice and significantly, i.e. 4.7-fold (P<0.01), higher brain uptake, relative to wild-type animals, in Mdr1a/b(−/−)Bcrp1(−/−) mice. This was consistent with HM30181 being at microdoses a dual substrate of Pgp and breast cancer resistance protein (Bcrp). In vitro autoradiography on low (EMT6) and high (EMT6Ar1.0) Pgp expressing murine breast tumour sections showed 1.9 times higher binding of [11C]HM30181 in EMT6Ar1.0 tumours (P<0.001) which was displaceable with unlabelled tariquidar, elacridar or HM30181 (1 μM). Our data suggest that HM30181 is not able to inhibit Pgp at the murine BBB at clinically feasible doses and that [11C]HM30181 is not suitable as a PET tracer to visualise cerebral Pgp expression levels. PMID:23022332

  10. 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.

  11. Brain network activity in monolingual and bilingual older adults.

    PubMed

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

    2015-01-01

    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.

  12. Brain network activity in monolingual and bilingual older adults.

    PubMed

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

    2015-01-01

    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. 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

  14. Assessment of murine brain tissue shrinkage caused by different histological fixatives using magnetic resonance and computed tomography imaging.

    PubMed

    Wehrl, Hans F; Bezrukov, Ilja; Wiehr, Stefan; Lehnhoff, Mareike; Fuchs, Kerstin; Mannheim, Julia G; Quintanilla-Martinez, Leticia; Kohlhofer, Ursula; Kneilling, Manfred; Pichler, Bernd J; Sauter, Alexander W

    2015-05-01

    Especially for neuroscience and the development of new biomarkers, a direct correlation between in vivo imaging and histology is essential. However, this comparison is hampered by deformation and shrinkage of tissue samples caused by fixation, dehydration and paraffin embedding. We used magnetic resonance (MR) imaging and computed tomography (CT) imaging to analyze the degree of shrinkage on murine brains for various fixatives. After in vivo imaging using 7 T MRI, animals were sacrificed and the brains were dissected and immediately placed in different fixatives, respectively: zinc-based fixative, neutral buffered formalin (NBF), paraformaldehyde (PFA), Bouin-Holland fixative and paraformaldehyde-lysine-periodate (PLP). The degree of shrinkage based on mouse brain volumes, radiodensity in Hounsfield units (HU), as well as non-linear deformations were obtained. The highest degree of shrinkage was observed for PLP (68.1%, P < 0.001), followed by PFA (60.2%, P<0.001) and NBF (58.6%, P<0.001). The zinc-based fixative revealed a low shrinkage with only 33.5% (P<0.001). Compared to NBF, the zinc-based fixative shows a slightly higher degree of deformations, but is still more homogenous than PFA. Tissue shrinkage can be monitored non-invasively with CT and MR. Zinc-based fixative causes the smallest degree of brain shrinkage and only small deformations and is therefore recommended for in vivo ex vivo comparison studies.

  15. 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

  16. 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

  17. 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.

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

    PubMed Central

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

    2015-01-01

    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. 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.

  20. 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

  1. 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

  2. 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.

  3. Doublecortin expression levels in adult brain reflect neurogenesis.

    PubMed

    Couillard-Despres, Sebastien; Winner, Beate; Schaubeck, Susanne; Aigner, Robert; Vroemen, Maurice; Weidner, Norbert; Bogdahn, Ulrich; Winkler, Jürgen; Kuhn, Hans-Georg; Aigner, Ludwig

    2005-01-01

    Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain. Doublecortin (DCX) has recently been used as a marker for neurogenesis. However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors. Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis. Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth. Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation. We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis. Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions. PMID:15654838

  4. B7 homolog 3 aggravates brain injury in a murine model of Streptococcus pneumoniae-induced meningitis

    PubMed Central

    CHEN, XUQIN; WANG, YANPING; WANG, ZHEDONG; YAN, RUHONG; LIU, JIE; MENG, XIANGYING; LI, YAN; WANG, JIANGHUAI; WANG, JIAN

    2015-01-01

    Despite the application of antibiotics, Streptococcus pneumoniae (SP)-induced meningitis continues to be a life-threatening disease with a high fatality rate and an elevated risk of serious neurological sequelae, particularly in developing countries. In this study, the contribution of the co-stimulatory molecule B7 homolog 3 (B7-H3) to the pathogenesis of experimental SP-induced meningitis was investigated. Mice were challenged with the intracerebroventricular injection of serotype 3 SP with or without B7-H3. The clinical status of mice with SP-induced meningitis was examined by body weight loss and spontaneous motor activity with neurological scoring. Coronal brain sections were analyzed by counting Nissl-positive neurons and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells. Protein expression of neuron-specific enolase (NSE) and S100B in brain tissues was examined with immunohistochemical staining. All experiments were performed in a randomized and blinded setting. By the intracerebroventricular injection of SP suspension, a murine model of pneumococcal meningitis was successfully established. In this SP-induced meningitis model, B7-H3 deteriorated the clinical status, as manifested by a decreased neurological score and increased body weight loss. Following the B7-H3 challenge, the number of Nissl-positive cells decreased and TUNEL-stained positive cells increased in the brain tissues of mice with SP meningitis, which demonstrates the enhancement of neuronal necrosis and apoptosis, respectively. Protein expression of NSE was decreased, while that of S100B was increased. These in vivo findings indicate that B7-H3 aggravates brain injury during the pathological process of experimental SP-induced meningitis. PMID:26136926

  5. 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.

  6. A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research

    PubMed Central

    Abulseoud, Osama A.; Tye, Susannah J.; Hosain, Md Kamal; Berk, Michael

    2013-01-01

    Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented. PMID:27170861

  7. Protective role of brain water channel AQP4 in murine cerebral malaria

    PubMed Central

    Promeneur, Dominique; Lunde, Lisa Kristina; Amiry-Moghaddam, Mahmood; Agre, Peter

    2013-01-01

    Tragically common among children in sub-Saharan Africa, cerebral malaria is characterized by rapid progression to coma and death. In this study, we used a model of cerebral malaria appearing in C57BL/6 WT mice after infection with the rodent malaria parasite Plasmodium berghei ANKA. Expression and cellular localization of the brain water channel aquaporin-4 (AQP4) was investigated during the neurological syndrome. Semiquantitative real-time PCR comparing uninfected and infected mice showed a reduction of brain AQP4 transcript in cerebral malaria, and immunoblots revealed reduction of brain AQP4 protein. Reduction of brain AQP4 protein was confirmed in cerebral malaria by quantitative immunogold EM; however, polarized distribution of AQP4 at the perivascular and subpial astrocyte membranes was not altered. To further examine the role of AQP4 in cerebral malaria, WT mice and littermates genetically deficient in AQP4 were infected with P. berghei. Upon development of cerebral malaria, WT and AQP4-null mice exhibited similar increases in width of perivascular astroglial end-feet in brain. Nevertheless, the AQP4-null mice exhibited more severe signs of cerebral malaria with greater brain edema, although disruption of the blood–brain barrier was similar in both groups. In longitudinal studies, cerebral malaria appeared nearly 1 d earlier in the AQP4-null mice, and reduced survival was noted when chloroquine rescue was attempted. We conclude that the water channel AQP4 confers partial protection against cerebral malaria. PMID:23277579

  8. An empirical EEG analysis in brain death diagnosis for adults.

    PubMed

    Chen, Zhe; Cao, Jianting; Cao, Yang; Zhang, Yue; Gu, Fanji; Zhu, Guoxian; Hong, Zhen; Wang, Bin; Cichocki, Andrzej

    2008-09-01

    Electroencephalogram (EEG) is often used in the confirmatory test for brain death diagnosis in clinical practice. Because EEG recording and monitoring is relatively safe for the patients in deep coma, it is believed to be valuable for either reducing the risk of brain death diagnosis (while comparing other tests such as the apnea) or preventing mistaken diagnosis. The objective of this paper is to study several statistical methods for quantitative EEG analysis in order to help bedside or ambulatory monitoring or diagnosis. We apply signal processing and quantitative statistical analysis for the EEG recordings of 32 adult patients. For EEG signal processing, independent component analysis (ICA) was applied to separate the independent source components, followed by Fourier and time-frequency analysis. For quantitative EEG analysis, we apply several statistical complexity measures to the EEG signals and evaluate the differences between two groups of patients: the subjects in deep coma, and the subjects who were categorized as brain death. We report statistically significant differences of quantitative statistics with real-life EEG recordings in such a clinical study, and we also present interpretation and discussions on the preliminary experimental results.

  9. Immunotherapy of a murine T cell lymphoma localized to the brain.

    PubMed

    Ghant, V K; Hiramoto, N S; Gillespie, G Y; Gauthier, D K; Hiramoto, R N

    2000-03-01

    Mouse YC8 T cell lymphoma was used as a model to determine whether an effective immunotherapy procedure could be devised for the treatment of lymphoma localized to the brain. Implantation of 5 x 10(4) YC8 cells into the left cerebral hemisphere induced rapid loss of the animal's body weight. Severe loss of weight and early deaths were observed in the untreated control group. Although resistance can be conferred to the brain by immunization of naive BALB/c mice, adoptive chemoimmunotherapy procedures were surprisingly not effective in inducing remissions in animals with lymphoma confined to the brain. Even passive transfer of effector cells from immunized, tumor resistant donor animals combined with systemic IL-2 treatment did not impart resistance to recipients with brain tumors. However, regression of the intracranial tumor and apparent cures could be accomplished, when ex vivo cultured effector cells were transferred intravenously.

  10. Brain angioarchitecture and intussusceptive microvascular growth in a murine model of Krabbe disease.

    PubMed

    Giacomini, Arianna; Ackermann, Maximilian; Belleri, Mirella; Coltrini, Daniela; Nico, Beatrice; Ribatti, Domenico; Konerding, Moritz A; Presta, Marco; Righi, Marco

    2015-10-01

    Defects of the angiogenic process occur in the brain of twitcher mouse, an authentic model of human Krabbe disease caused by genetic deficiency of lysosomal β-galactosylceramidase (GALC), leading to lethal neurological dysfunctions and accumulation of neurotoxic psychosine in the central nervous system. Here, quantitative computational analysis was used to explore the alterations of brain angioarchitecture in twitcher mice. To this aim, customized ImageJ routines were used to assess calibers, amounts, lengths and spatial dispersion of CD31(+) vessels in 3D volumes from the postnatal frontal cortex of twitcher animals. The results showed a decrease in CD31 immunoreactivity in twitcher brain with a marked reduction in total vessel lengths coupled with increased vessel fragmentation. No significant changes were instead observed for the spatial dispersion of brain vessels throughout volumes or in vascular calibers. Notably, no CD31(+) vessel changes were detected in twitcher kidneys in which psychosine accumulates at very low levels, thus confirming the specificity of the effect. Microvascular corrosion casting followed by scanning electron microscopy morphometry confirmed the presence of significant alterations of the functional angioarchitecture of the brain cortex of twitcher mice with reduction in microvascular density, vascular branch remodeling and intussusceptive angiogenesis. Intussusceptive microvascular growth, confirmed by histological analysis, was paralleled by alterations of the expression of intussusception-related genes in twitcher brain. Our data support the hypothesis that a marked decrease in vascular development concurs to the onset of neuropathological lesions in twitcher brain and suggest that neuroinflammation-driven intussusceptive responses may represent an attempt to compensate impaired sprouting angiogenesis.

  11. Murine Typhus

    PubMed Central

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

  12. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging

    PubMed Central

    Aikawa, Hiroaki; Hayashi, Mitsuhiro; Ryu, Shoraku; Yamashita, Makiko; Ohtsuka, Naoto; Nishidate, Masanobu; Fujiwara, Yasuhiro; Hamada, Akinobu

    2016-01-01

    In the development of anticancer drugs, drug concentration measurements in the target tissue have been thought to be crucial for predicting drug efficacy and safety. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is commonly used for determination of average drug concentrations; however, complete loss of spatial information in the target tissue occurs. Mass spectrometry imaging (MSI) has been recently applied as an innovative tool for detection of molecular distribution of pharmacological agents in heterogeneous targets. This study examined the intra-brain transitivity of alectinib, a novel anaplastic lymphoma kinase inhibitor, using a combination of matrix-assisted laser desorption ionization–MSI and LC-MS/MS techniques. We first analyzed the pharmacokinetic profiles in FVB mice and then examined the effect of the multidrug resistance protein-1 (MDR1) using Mdr1a/b knockout mice including quantitative distribution of alectinib in the brain. While no differences were observed between the mice for the plasma alectinib concentrations, diffuse alectinib distributions were found in the brain of the Mdr1a/b knockout versus FVB mice. These results indicate the potential for using quantitative MSI for clarifying drug distribution in the brain on a microscopic level, in addition to suggesting a possible use in designing studies for anticancer drug development and translational research. PMID:27026287

  13. Herpes simplex virus-1 replication in histiotypic rotation-mediated reaggregated murine brain.

    PubMed

    Fowler, S L; Forbes, R A

    1995-04-01

    Inbred mouse strains exhibit varying susceptibilities to severe herpes simplex virus (HSV)-1-related neurologic disease. HSV-1 replication was examined in neural tissue obtained from mouse strains susceptible (A/J, SJL), moderately resistant (Balb/c), or resistant (C57BL/6) to severe HSV-1 disease. Reaggregated brain cultures were prepared from mechanically dissociated fetal mouse brains maintained with constant rotation. The resulting aggregates each contain neurons, astrocytes, oligodendrocytes, and microglia. These were inoculated with 10(-2)-10(4) plaque-forming units (pfu) HSV-1 MacIntyre/aggregate. Aggregates and media were harvested at 24, 48, 72, and 96 hr post-inoculation (p.i.) and assayed for virus production by plaque titration. Brain cultures prepared from A/J, SJL, Balb/c, and C57BL/6 mice supported HSV-1 replication equally well: by 96 hr p.i., titers of 10(6) pfu/ml were produced by each strain at each inoculum. ID50s were similar for A/J and C57BL/6 cultures. There was no increased capacity for HSV-1 replication or for permissiveness for HSV-1 infection in histiotypic brain cultures from mouse strains susceptible to severe HSV-1 disease.

  14. 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

  15. 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.

  16. 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

  17. Narrative skills following traumatic brain injury in children and adults.

    PubMed

    Biddle, K R; McCabe, A; Bliss, L S

    1996-01-01

    Personal narratives serve an important function in virtually all societies (Peterson & McCabe, 1991). Through narratives individuals make sense of their experiences and represent themselves to others (Bruner, 1990). The ability to produce narratives has been linked to academic success (Feagans, 1982). Persons who have sustained a traumatic brain injury (TBI) are at risk for impaired narrative ability (Dennis, 1991). However, a paucity of information exists on the discourse abilities of persons with TBI. This is partly due to a lack of reliable tools with which to assess narrative discourse. The present study utilized dependency analysis (Deese, 1984) to document and describe the narrative discourse impairments of children and adults with TBI. Ten children (mean age 12;0) and 10 adults (mean age 35;2) were compared with matched controls. Dependency analysis reliably differentiated the discourse of the individuals with TBI from their controls. Individuals with TBI were significantly more dysfluent than their matched controls. Furthermore, their performance on the narrative task revealed a striking listener burden.

  18. Effects of pre- and neonatal exposure to bisphenol A on murine brain development.

    PubMed

    Tando, So; Itoh, Kyoko; Yaoi, Takeshi; Ikeda, Jun; Fujiwara, Yasuhiro; Fushiki, Shinji

    2007-07-01

    Bisphenol A (BPA), known as an environmental endocrine disrupter, is widely used in industry and dentistry. We investigated the effects of fetal and neonatal exposure to bisphenol A (BPA) on the brain development of mice. The density of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons in substantia nigra was significantly decreased in BPA-exposed female mice (3 microg/g powder food), but not in the male mice, as compared with that of the control mice. The densities of calbindin D-28 K-, calretinin- and parvalbumin-IR neurons in the cerebral cortex were not different between BPA-exposed and the control mice. The present study indicates that chronic exposure of BPA during prenatal and neonatal periods causes a decrease of TH-positive neurons in substantia nigra only in female mice brain. PMID:17113258

  19. In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas.

    PubMed

    Tremblay, Jacob R; LeBon, Jeanne M; Luo, Angela; Quijano, Janine C; Wedeken, Lena; Jou, Kevin; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2016-01-01

    Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. However, it is still unknown whether stem and progenitor cells exist in the adult pancreas. Research strategies using cre-lox lineage-tracing in adult mice have yielded results that either support or refute the idea that beta cells can be generated from the ducts, the presumed location where adult pancreatic progenitors may reside. These in vivo cre-lox lineage-tracing methods, however, cannot answer the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell. To begin addressing this technical gap, we devised 3-dimensional colony assays for pancreatic progenitors. Soon after our initial publication, other laboratories independently developed a similar, but not identical, method called the organoid assay. Compared to the organoid assay, our method employs methylcellulose, which forms viscous solutions that allow the inclusion of extracellular matrix proteins at low concentrations. The methylcellulose-containing assays permit easier detection and analyses of progenitor cells at the single-cell level, which are critical when progenitors constitute a small sub-population, as is the case for many adult organ stem cells. Together, results from several laboratories demonstrate in vitro self-renewal and multi-lineage differentiation of pancreatic progenitor-like cells from mice. The current protocols describe two methylcellulose-based colony assays to characterize mouse pancreatic progenitors; one contains a commercial preparation of murine extracellular matrix proteins and the other an artificial extracellular matrix protein known as a laminin hydrogel. The techniques shown here are 1) dissociation of the pancreas and sorting of CD133(+)Sox9/EGFP(+) ductal cells from adult mice, 2) single cell manipulation of the sorted cells, 3) single colony analyses using microfluidic q

  20. Infections of neonatal and adult mice with murine CMV HaNa1 strain upon oronasal inoculation: New insights in the pathogenesis of natural primary CMV infections.

    PubMed

    Xiang, Jun; Zhang, Shunchuan; Nauwynck, Hans

    2016-01-01

    In healthy individuals, naturally acquired infections of human cytomegalovirus (HCMV) are generally asymptomatic. Animal models mimicking the natural primary HCMV infections in infants and adults are scarce. Here, neonatal and adult BALB/c mice were inoculated oronasally with a Belgian isolate HaNa1 of murine cytomegalovirus (MCMV). None of the mice showed clinical symptoms. In neonatal mice, a typical systemic infection occurred. In adult mice, viral replication was restricted to the nasal mucosa and submandibular glands. Infectious virus was not detected in trachea, oral mucosa, pharynx, esophagus, small intestines of both neonatal and adult mice at all time points. Nose was demonstrated to be the entry site. Double immunofluorescence staining showed that in nose infected cells were olfactory neurons and sustentacular cells in olfactory epithelium and were macrophages and dendritic cells in nasopharynx-associated lymphoid tissues (NALT). Neonatal and adult mice developed similar antibody response pattern, though former magnitude was lower. In summary, we have established intranasal (without anesthesia) infections of neonatal and adult mice with murine CMV HaNa1 strain, which mimic the range and extent of virus replication during natural primary HCMV infections in healthy infants and adults. These findings might bring new insights in the pathogenesis of natural primary CMV infections. PMID:26474525

  1. Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome.

    PubMed

    Cortelazzo, Alessio; De Felice, Claudio; Guerranti, Roberto; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Scalabrì, Francesco; Madonna, Michele; Filosa, Stefania; Della Giovampaola, Cinzia; Capone, Antonietta; Durand, Thierry; Mirasole, Cristiana; Zolla, Lello; Valacchi, Giuseppe; Ciccoli, Lucia; Guy, Jacky; D'Esposito, Maurizio; Hayek, Joussef

    2016-04-01

    Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5.

  2. 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

  3. Imaging of Angiotropism/Vascular Co-Option in a Murine Model of Brain Melanoma: Implications for Melanoma Progression along Extravascular Pathways

    PubMed Central

    Bentolila, Laurent A.; Prakash, Roshini; Mihic-Probst, Daniela; Wadehra, Madhuri; Kleinman, Hynda K.; Carmichael, Thomas S.; Péault, Bruno; Barnhill, Raymond L.; Lugassy, Claire

    2016-01-01

    Angiotropism/pericytic mimicry and vascular co-option involve tumor cell interactions with the abluminal vascular surface. These two phenomena may be closely related. However, investigations of the two processes have developed in an independent fashion and different explanations offered as to their biological nature. Angiotropism describes the propensity of tumor cells to spread distantly via continuous migration along abluminal vascular surfaces, or extravascular migratory metastasis (EVMM). Vascular co-option has been proposed as an alternative mechanism by which tumors cells may gain access to a blood supply. We have used a murine brain melanoma model to analyze the interactions of GFP human melanoma cells injected into the mouse brain with red fluorescent lectin-labeled microvascular channels. Results have shown a striking spread of melanoma cells along preexisting microvascular channels and features of both vascular co-option and angiotropism/pericytic mimicry. This study has also documented the perivascular expression of Serpin B2 by angiotropic melanoma cells in the murine brain and in human melanoma brain metastases. Our findings suggest that vascular co-option and angiotropism/pericytic mimicry are closely related if not identical processes. Further studies are needed in order to establish whether EVMM is an alternative form of cancer metastasis in addition to intravascular cancer dissemination. PMID:27048955

  4. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention. PMID:26194112

  5. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

  6. Ablating hedgehog signaling in tenocytes during development impairs biomechanics and matrix organization of the adult murine patellar tendon enthesis.

    PubMed

    Breidenbach, Andrew P; Aschbacher-Smith, Lindsey; Lu, Yinhui; Dyment, Nathaniel A; Liu, Chia-Feng; Liu, Han; Wylie, Chris; Rao, Marepalli; Shearn, Jason T; Rowe, David W; Kadler, Karl E; Jiang, Rulang; Butler, David L

    2015-08-01

    Restoring the native structure of the tendon enthesis, where collagen fibers of the midsubstance are integrated within a fibrocartilaginous structure, is problematic following injury. As current surgical methods fail to restore this region adequately, engineers, biologists, and clinicians are working to understand how this structure forms as a prerequisite to improving repair outcomes. We recently reported on the role of Indian hedgehog (Ihh), a novel enthesis marker, in regulating early postnatal enthesis formation. Here, we investigate how inactivating the Hh pathway in tendon cells affects adult (12-week) murine patellar tendon (PT) enthesis mechanics, fibrocartilage morphology, and collagen fiber organization. We show that ablating Hh signaling resulted in greater than 100% increased failure insertion strain (0.10 v. 0.05 mm/mm, p<0.01) as well as sub-failure biomechanical deficiencies. Although collagen fiber orientation appears overtly normal in the midsubstance, ablating Hh signaling reduces mineralized fibrocartilage by 32%, leading to less collagen embedded within mineralized tissue. Ablating Hh signaling also caused collagen fibers to coalesce at the insertion, which may explain in part the increased strains. These results indicate that Ihh signaling plays a critical role in the mineralization process of fibrocartilaginous entheses and may be a novel therapeutic to promote tendon-to-bone healing.

  7. 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.

  8. 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.

  9. Environmental enrichment is associated with rapid volumetric brain changes in adult mice.

    PubMed

    Scholz, Jan; Allemang-Grand, Rylan; Dazai, Jun; Lerch, Jason P

    2015-04-01

    Environmental enrichment is a model of increased structural brain plasticity. Previous histological observations have shown molecular and cellular changes in a few pre-determined areas of the rodent brain. However, little is known about the time course of enrichment-induced brain changes and how they distribute across the whole brain. Here we expose adult mice to three weeks of environmental enrichment using a novel re-configurable maze design. In-vivo MRI shows volumetric brain changes in brain areas related to spatial memory, navigation, and sensorimotor experience, such as the hippocampal formation and the sensorimotor cortex. Evidence from a second cohort of mice indicates that these plastic changes might occur as early as 24h after exposure. This suggests that novel experiences are powerful modulators of plasticity even in the adult brain. Understanding and harnessing the underlying molecular mechanisms could advance future treatments of neurological disease.

  10. Differences in cadmium transport to the testis, epididymis, and brain in cadmium-sensitive and -resistant murine strains 129/J and A/J.

    PubMed

    King, L M; Banks, W A; George, W J

    1999-05-01

    Although most animals with scrotal testes are susceptible to cadmium-induced testicular toxicity, strain-related differences are seen in mice. Resistant murine strains demonstrate a decreased cadmium concentration in the testis and also in the epididymis and seminal vesicle. In this study we analyzed cadmium transport into tissues with a vascular barrier, the testis, epididymis, and brain, in an attempt to characterize the mechanisms of strain resistance to cadmium-induced testicular toxicity. In the resistant murine strain A/J, 109Cd transport (administered as 109CdCl2) was significantly attenuated in the testis, epididymis, and brain, when compared to the sensitive murine strain 129/J. The unidirectional influx constant (Ki, in microliter g-1 min-1) for 109Cd was 0.01929 in the A/J testis as compared with 1.174 in the 129/J testis (P <.0001). The percentage of a 109Cd dose that reached the A/J testis by 60 min was over 10 times less than that which reached the 129/J testis. The transport system used by cadmium in the 129/J testis was saturable, with 20 microM unlabeled cadmium chloride inhibiting transport by over 60%. The transporter was competitively inhibited by zinc (P =. 00017), but not by calcium, indicating a specificity in ion transport. Studies with isolated tubules and analysis of testicular fluid compartments demonstrated no significant difference in cadmium uptake or efflux between the strains when corrected for the amount of 109Cd entering the testis. Therefore, murine strain differences in testicular sensitivity to cadmium appear to be related to the variable presence of a transport system for cadmium in the testicular vasculature. PMID:10215659

  11. Tissue-specific regulation of erythropoietin production in the murine kidney, brain, and uterus.

    PubMed

    Chikuma, M; Masuda, S; Kobayashi, T; Nagao, M; Sasaki, R

    2000-12-01

    Erythropoietin (Epo) produced by the kidney regulates erythropoiesis. Recent evidence suggests that Epo in the cerebrum prevents neuron death and Epo in the uterus induces estrogen (E(2))-dependent uterine angiogenesis. To elucidate how Epo expression is regulated in these tissues, ovariectomized mice were given E(2) and/or exposed to hypoxia, and the temporal patterns of Epo mRNA levels were examined. Epo mRNA levels in the kidney and cerebrum were elevated markedly within 4 h after exposure to hypoxia. Although the elevated level of Epo mRNA in the kidney decreased markedly within 8 h despite continuous hypoxia, the high level in the cerebrum was sustained for > or = 24 h, indicating that downregulation operates in the kidney but not in the brain. E(2) transiently induced Epo mRNA in the uterus but not in the kidney and cerebrum. Interestingly, the uterine Epo mRNA was hypoxia inducible only in the presence of E(2). Thus Epo expression appears to be regulated in a tissue-specific manner, endorsing the tissue-specific functions of Epo.

  12. 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

  13. Systemic Inflammatory Effects of Traumatic Brain Injury, Femur Fracture, and Shock: An Experimental Murine Polytrauma Model

    PubMed Central

    Probst, C.; Mirzayan, M. J.; Mommsen, P.; Zeckey, C.; Tegeder, T.; Geerken, L.; Maegele, M.; Samii, A.; van Griensven, M.

    2012-01-01

    Objective. Despite broad research in neurotrauma and shock, little is known on systemic inflammatory effects of the clinically most relevant combined polytrauma. Experimental investigation in an animal model may provide relevant insight for therapeutic strategies. We describe the effects of a combined injury with respect to lymphocyte population and cytokine activation. Methods. 45 male C57BL/6J mice (mean weight 27 g) were anesthetized with ketamine/xylazine. Animals were subjected to a weight drop closed traumatic brain injury (WD-TBI), a femoral fracture and hemorrhagic shock (FX-SH). Animals were subdivided into WD-TBI, FX-SH and combined trauma (CO-TX) groups. Subjects were sacrificed at 96 h. Blood was analysed for cytokines and by flow cytometry for lymphocyte populations. Results. Mortality was 8%, 13% and 47% for FX-SH, WD-TBI and CO-TX groups (P < 0.05). TNFα (11/13/139 for FX-SH/WD-TBI/CO-TX; P < 0.05), CCL2 (78/96/227; P < 0.05) and IL-6 (16/48/281; P = 0.05) showed significant increases in the CO-TX group. Lymphocyte populations results for FX-SH, WD-TBI and CO-TX were: CD-4 (31/21/22; P = n.s.), CD-8 (7/28/34, P < 0.05), CD-4-CD-8 (11/12/18; P = n.s.), CD-56 (36/7/8; P < 0.05). Conclusion. This study shows that a combination of closed TBI and femur-fracture/ shock results in an increase of the humoral inflammation. More attention to combined injury models in inflammation research is indicated. PMID:22529516

  14. A model utilizing adult murine stem cells for creation of personalized islets for transplantation.

    PubMed

    Wang, J; Song, L J; Gerber, D A; Fair, J H; Rice, L; LaPaglia, M; Andreoni, K A

    2004-05-01

    Clinical islet cell transplantation has demonstrated great promise for diabetes treatment. Two major obstacles are the organ donor shortage and the immunoresponse. The purpose of this study was to create a model using the patient's own adult stem cell sources, possibly in combination with non-self cells, such as pancreatic, hepatic, or embryonic stem cells, to create "personalized" islets. We hypothesize that the reconstructed islets have the normal capability to produce insulin and glucagon with reduced immunoresponses after transplantation. Stem cells are a proliferating population of master cells that have the ability for self-renewal and multilineage differentiation. The recently developed photolithograph-based, biologic, microelectromechanic system (BioMEMS) technique supplies a useful tool for biomedical applications. Our lab has developed a novel method that integrates the adult stem cell and BioMEMS to reconstruct personalized islets. We selected islet-derived progenitor cells (IPC) for repairing and reconstructing STZ-diabetic islets. A6(+)/PYY(+) or A6(+)/ngn3(+) cells were selected to manipulate the neoislets. After 3 to 4 weeks in culture, the reconstructed cells formed islet-like clusters containing insulin or glucagon producing cells. The pilot results showed the ability of these reconstructed islets to correct hyperglycemia when transplanted into a STZ-diabetic isograft mouse model. Although several technical problems remain with the mouse model, namely, the difficulty to collect enough islets from a single mouse because of animal size, the mouse isograft model is suitable for personalized islet development.

  15. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium.

    PubMed

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J; Abreu Paiva, Marta S; Habib, Josef; Macaulay, Iain; de Smith, Adam J; al-Beidh, Farah; Sampson, Robert; Lumbers, R Thomas; Rao, Pulivarthi; Harding, Sian E; Blakemore, Alexandra I F; Jacobsen, Sten Eirik; Barahona, Mauricio; Schneider, Michael D

    2015-05-18

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα(+) cells. Clonal progeny of single Sca1(+) SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα(-) cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα(+)/CD31(-) cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα(-)/CD31(+) cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1(+) stem/progenitor cell.

  16. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium

    PubMed Central

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J.; Abreu Paiva, Marta S.; Habib, Josef; Macaulay, Iain; de Smith, Adam J.; al-Beidh, Farah; Sampson, Robert; Lumbers, R. Thomas; Rao, Pulivarthi; Harding, Sian E.; Blakemore, Alexandra I. F.; Eirik Jacobsen, Sten; Barahona, Mauricio; Schneider, Michael D.

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT–PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα+ cells. Clonal progeny of single Sca1+ SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα− cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα+/CD31− cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα−/CD31+ cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem/progenitor cell. PMID:25980517

  17. Regeneration of central cholinergic neurones in the adult rat brain.

    PubMed

    Svendgaard, N A; Björklund, A; Stenevi, U

    1976-01-30

    The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together

  18. Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways.

    PubMed

    Gianotti, Ambra; Ferrera, Loretta; Philp, Amber R; Caci, Emanuela; Zegarra-Moran, Olga; Galietta, Luis J V; Flores, Carlos A

    2016-06-15

    Defective epithelial chloride secretion occurs in humans with cystic fibrosis (CF), a genetic defect due to loss of function of CFTR, a cAMP-activated chloride channel. In the airways, absence of an active CFTR causes a severe lung disease. In mice, genetic ablation of CFTR function does not result in similar lung pathology. This may be due to the expression of an alternative chloride channel which is activated by calcium. The most probable protein performing this function is TMEM16A, a calcium-activated chloride channel (CaCC). Our aim was to assess the relative contribution of CFTR and TMEM16A to chloride secretion in adult mouse trachea. For this purpose we tested pharmacological inhibitors of chloride channels in normal and CF mice. The amplitude of the cAMP-activated current was similar in both types of animals and was not affected by a selective CFTR inhibitor. In contrast, a CaCC inhibitor (CaCCinh-A01) strongly blocked the cAMP-activated current as well as the calcium-activated chloride secretion triggered by apical UTP. Although control experiments revealed that CaCCinh-A01 also shows inhibitory activity on CFTR, our results indicate that transepithelial chloride secretion in adult mouse trachea is independent of CFTR and that another channel, possibly TMEM16A, performs both cAMP- and calcium-activated chloride transport. The prevalent function of a non-CFTR channel may explain the absence of a defect in chloride transport in CF mice. PMID:27063443

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Organotypical tissue cultures from adult murine colon as an in vitro model of intestinal mucosa

    PubMed Central

    Bareiss, Petra M.; Metzger, Marco; Sohn, Kai; Rupp, Steffen; Frick, Julia S.; Autenrieth, Ingo B.; Lang, Florian; Schwarz, Heinz; Skutella, Thomas

    2008-01-01

    Together with animal experiments, organotypical cell cultures are important models for analyzing cellular interactions of the mucosal epithelium and pathogenic mechanisms in the gastrointestinal tract. Here, we introduce a three-dimensional culture model from the adult mouse colon for cell biological investigations in an in vivo-like environment. These explant cultures were cultured for up to 2 weeks and maintained typical characteristics of the intestinal mucosa, including a high-prismatic epithelium with specific epithelial cell-to-cell connections, a basal lamina and various connective tissue cell types, as analyzed with immunohistological and electron microscopic methods. The function of the epithelium was tested by treating the cultures with dexamethasone, which resulted in a strong upregulation of the serum- and glucocorticoid-inducible kinase 1 similar to that found in vivo. The culture system was investigated in infection experiments with the fungal pathogen Candida albicans. Wildtype but not Δcph1/Δefg1-knockout Candida adhered to, penetrated and infiltrated the epithelial barrier. The results demonstrate the potential usefulness of this intestinal in vitro model for studying epithelial cell-cell interactions, cellular signaling and microbiological infections in a three-dimensional cell arrangement. PMID:18320204

  4. Glomerular parietal epithelial cells of adult murine kidney undergo EMT to generate cells with traits of renal progenitors

    PubMed Central

    G, Swetha; Chandra, Vikash; Phadnis, Smruti; Bhonde, Ramesh

    2011-01-01

    Abstract Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic phenotype in response to renal injury. However, the mechanism of de-differentiation in GPECs and the underlying cellular processes are not fully understood. In the present study, we show that cultured GPECs of adult murine kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and immunostaining of these clonogenic cells demonstrate that they exhibit metastable phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7, C-Ret) genes in these cells, indicating their bipotent progenitor status. Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression of renal progenitor markers reflecting the correlation between EMT and acquired stemness in these cells. Additional in vitro renal commitment assays confirmed their functional staminality. When injected into E13.5 kidney rudiments, the cells incorporated into the developing kidney primordia and co-culture with E13.5 spinal cord resulted in branching and tubulogenesis in these cells. When implanted under renal capsule of unilaterally nephrectomized mice, these cells differentiated into immature glomeruli and vascular ducts. Our study demonstrates that EMT plays a major role in imparting plasticity to terminally differentiated GPECs by producing metastable cells with traits of kidney progenitors. The present study would improve our understanding on epithelial cell plasticity, furthering our knowledge of its role in renal repair and regeneration. PMID:19840197

  5. Correlates of Depression in Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Lynch, Ruth Torkelson

    2006-01-01

    Using Pearlin's stress process model, this study examined correlates of depression in 170 adult siblings of persons with traumatic brain injury (TBI). Approximately 39% of adult sibling participants evinced "Center for Epidemiologic Studies-Depression" (CES-D; Radloff, 1977) scores indicating clinically significant depressive symptoms. Background…

  6. 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…

  7. 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

  8. Conditional Knockout of Myocyte Focal Adhesion Kinase Abrogates Ischemic Preconditioning in Adult Murine Hearts

    PubMed Central

    Perricone, Adam J.; Bivona, Benjamin J.; Jackson, Fannie R.; Vander Heide, Richard S.

    2013-01-01

    Background Our laboratory has previously demonstrated the importance of a cytoskeletal‐based survival signaling pathway using in vitro models of ischemia/reperfusion (IR). However, the importance of this pathway in mediating stress‐elicited survival signaling in vivo is unknown. Methods and Results The essential cytoskeletal signaling pathway member focal adhesion kinase (FAK) was selectively deleted in adult cardiac myocytes using a tamoxifen‐inducible Cre‐Lox system (α‐MHC‐MerCreMer). Polymerase chain reaction (PCR) and Western blot were performed to confirm FAK knockout (KO). All mice were subjected to a 40‐minute coronary occlusion followed by 24 hours of reperfusion. Ischemic preconditioning (IP) was performed using a standard protocol. Control groups included wild‐type (WT) and tamoxifen‐treated α‐MHC‐MerCreMer+/−/FAKWT/WT (experimental control) mice. Infarct size was expressed as a percentage of the risk region. In WT mice IP significantly enhanced the expression of activated/phosphorylated FAK by 36.3% compared to WT mice subjected to a sham experimental protocol (P≤0.05; n=6 hearts [sham], n=4 hearts [IP]). IP significantly reduced infarct size in both WT and experimental control mice (43.7% versus 19.8%; P≤0.001; 44.7% versus 17.5%; P≤0.001, respectively). No difference in infarct size was observed between preconditioned FAK KO and nonpreconditioned controls (37.1% versus 43.7% versus 44.7%; FAK KO versus WT versus experimental control; P=NS). IP elicited a 67.2%/88.8% increase in activated phosphatidylinositol‐3‐kinase (PI3K) p85/activated Akt expression in WT mice, but failed to enhance the expression of either in preconditioned FAK KO mice. Conclusions Our results indicate that FAK is an essential mediator of IP‐elicited cardioprotection and provide further support for the hypothesis that cytoskeletal‐based signaling is an important component of stress‐elicited survival signaling. PMID:24080910

  9. Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells

    PubMed Central

    Kizil, Caghan; Brand, Michael

    2011-01-01

    The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. Therefore, investigating the zebrafish brain can help not only to elucidate the molecular mechanisms of widespread adult neurogenesis in a vertebrate species, but also to design therapies in humans with what we learn from this teleost. Yet, understanding the cellular behavior and molecular programs underlying different biological processes in the adult zebrafish brain requires techniques that allow manipulation of gene function. As a complementary method to the currently used misexpression techniques in zebrafish, such as transgenic approaches or electroporation-based delivery of DNA, we devised a cerebroventricular microinjection (CVMI)-assisted knockdown protocol that relies on vivo morpholino oligonucleotides, which do not require electroporation for cellular uptake. This rapid method allows uniform and efficient knockdown of genes in the ventricular cells of the zebrafish brain, which contain the neurogenic progenitors. We also provide data on the use of CVMI for growth factor administration to the brain – in our case FGF8, which modulates the proliferation rate of the ventricular cells. In this paper, we describe the CVMI method and discuss its potential uses in zebrafish. PMID:22076157

  10. Interferon-gamma but not TNF alpha promotes neuronal differentiation and neurite outgrowth of murine adult neural stem cells.

    PubMed

    Wong, Galaxy; Goldshmit, Yona; Turnley, Ann M

    2004-05-01

    Neural trauma, such as traumatic brain injury or stroke, results in a vigorous inflammatory response at and near the site of injury, with cytokine production by endogenous glial cells and invading immune cells. Little is known of the effect that these cytokines have on neural stem cell function. Here we examine the effects of two inflammatory cytokines, interferon-gamma (IFN gamma) and tumour necrosis factor-alpha (TNFalpha), on adult neural stem cells. Neural stem cells grown in the presence of either cytokine failed to generate neurospheres. Cytotoxicity assays showed that TNF alpha but not IFN gamma was toxic to the neural stem cells under proliferative conditions. Under differentiating conditions, neither cytokine was toxic; however, IFN gamma enhanced neuronal differentiation, rapidly increasing beta III-tubulin positive cell numbers 3-4 fold and inhibiting astrocyte generation. Furthermore, neurite outgrowth and the number of neurites per neuron was enhanced in cells differentiated in the presence of IFN gamma. Therefore, both inflammatory cytokines examined have substantial, but different effects on neural stem cell function and suggests that regulation of the inflammatory environment following brain injury may influence the ability of neural stem cells to repair the damage. PMID:15081598

  11. 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

  12. 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

    2016-04-21

    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.

  13. 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…

  14. PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.

    PubMed

    Henriksson, Richard; Bäckman, Cristina M; Harvey, Brandon K; Kadyrova, Helena; Bazov, Igor; Shippenberg, Toni S; Bakalkin, Georgy

    2014-11-01

    The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders. PMID:25220237

  15. In vivo visualization and ex vivo quantification of murine breast cancer cells in the mouse brain using MRI cell tracking and electron paramagnetic resonance.

    PubMed

    Danhier, Pierre; Magat, Julie; Levêque, Philippe; De Preter, Géraldine; Porporato, Paolo E; Bouzin, Caroline; Jordan, Bénédicte F; Demeur, Gladys; Haufroid, Vincent; Feron, Olivier; Sonveaux, Pierre; Gallez, Bernard

    2015-03-01

    Cell tracking could be useful to elucidate fundamental processes of cancer biology such as metastasis. The aim of this study was to visualize, using MRI, and to quantify, using electron paramagnetic resonance (EPR), the entrapment of murine breast cancer cells labeled with superparamagnetic iron oxide particles (SPIOs) in the mouse brain after intracardiac injection. For this purpose, luciferase-expressing murine 4 T1-luc breast cancer cells were labeled with fluorescent Molday ION Rhodamine B SPIOs. Following intracardiac injection, SPIO-labeled 4 T1-luc cells were imaged using multiple gradient-echo sequences. Ex vivo iron oxide quantification in the mouse brain was performed using EPR (9 GHz). The long-term fate of 4 T1-luc cells after injection was characterized using bioluminescence imaging (BLI), brain MRI and immunofluorescence. We observed hypointense spots due to SPIO-labeled cells in the mouse brain 4 h after injection on T2 *-weighted images. Histology studies showed that SPIO-labeled cancer cells were localized within blood vessels shortly after delivery. Ex vivo quantification of SPIOs showed that less than 1% of the injected cells were taken up by the mouse brain after injection. MRI experiments did not reveal the development of macrometastases in the mouse brain several days after injection, but immunofluorescence studies demonstrated that these cells found in the brain established micrometastases. Concerning the metastatic patterns of 4 T1-luc cells, an EPR biodistribution study demonstrated that SPIO-labeled 4 T1-luc cells were also entrapped in the lungs of mice after intracardiac injection. BLI performed 6 days after injection of 4 T1-luc cells showed that this cell line formed macrometastases in the lungs and in the bones. Conclusively, EPR and MRI were found to be complementary for cell tracking applications. MRI cell tracking at 11.7 T allowed sensitive detection of isolated SPIO-labeled cells in the mouse brain, whereas EPR

  16. In vivo visualization and ex vivo quantification of murine breast cancer cells in the mouse brain using MRI cell tracking and electron paramagnetic resonance.

    PubMed

    Danhier, Pierre; Magat, Julie; Levêque, Philippe; De Preter, Géraldine; Porporato, Paolo E; Bouzin, Caroline; Jordan, Bénédicte F; Demeur, Gladys; Haufroid, Vincent; Feron, Olivier; Sonveaux, Pierre; Gallez, Bernard

    2015-03-01

    Cell tracking could be useful to elucidate fundamental processes of cancer biology such as metastasis. The aim of this study was to visualize, using MRI, and to quantify, using electron paramagnetic resonance (EPR), the entrapment of murine breast cancer cells labeled with superparamagnetic iron oxide particles (SPIOs) in the mouse brain after intracardiac injection. For this purpose, luciferase-expressing murine 4 T1-luc breast cancer cells were labeled with fluorescent Molday ION Rhodamine B SPIOs. Following intracardiac injection, SPIO-labeled 4 T1-luc cells were imaged using multiple gradient-echo sequences. Ex vivo iron oxide quantification in the mouse brain was performed using EPR (9 GHz). The long-term fate of 4 T1-luc cells after injection was characterized using bioluminescence imaging (BLI), brain MRI and immunofluorescence. We observed hypointense spots due to SPIO-labeled cells in the mouse brain 4 h after injection on T2 *-weighted images. Histology studies showed that SPIO-labeled cancer cells were localized within blood vessels shortly after delivery. Ex vivo quantification of SPIOs showed that less than 1% of the injected cells were taken up by the mouse brain after injection. MRI experiments did not reveal the development of macrometastases in the mouse brain several days after injection, but immunofluorescence studies demonstrated that these cells found in the brain established micrometastases. Concerning the metastatic patterns of 4 T1-luc cells, an EPR biodistribution study demonstrated that SPIO-labeled 4 T1-luc cells were also entrapped in the lungs of mice after intracardiac injection. BLI performed 6 days after injection of 4 T1-luc cells showed that this cell line formed macrometastases in the lungs and in the bones. Conclusively, EPR and MRI were found to be complementary for cell tracking applications. MRI cell tracking at 11.7 T allowed sensitive detection of isolated SPIO-labeled cells in the mouse brain, whereas EPR

  17. Essential role of brain-derived neurotrophic factor in adult hippocampal function

    PubMed Central

    Monteggia, Lisa M.; Barrot, Michel; Powell, Craig M.; Berton, Olivier; Galanis, Victor; Gemelli, Terry; Meuth, Sven; Nagy, Andreas; Greene, Robert W.; Nestler, Eric J.

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain. PMID:15249684

  18. Restricted nature of adult neural stem cells: re-evaluation of their potential for brain repair

    PubMed Central

    Obernier, Kirsten; Tong, Cheuk Ka; Alvarez-Buylla, Arturo

    2014-01-01

    Neural stem cells (NSCs) in the walls of the lateral ventricles continue to produce new neurons and oligodendrocytes throughout life. The identification of NSCs, long-range neuronal migration, and the integration of new neurons into fully formed mature neural circuits—all in the juvenile or adult brain—has dramatically changed concepts in neurodevelopment and suggests new strategies for brain repair. Yet, the latter has to be seen in perspective: NSCs in the adult are heterogeneous and highly regionally specified; young neurons derived from these primary progenitors migrate and integrate in specific brain regions. Neurogenesis appears to have a function in brain plasticity rather than brain repair. If similar processes could be induced in regions of the brain that are normally not a target of new neurons, therapeutic neuronal replacement may one day reinstate neural circuit plasticity and possibly repair broken neural circuits. PMID:24987325

  19. Sex, stress and the brain: interactive actions of hormones on the developing and adult brain.

    PubMed

    McEwen, B S

    2014-12-01

    The brain is a target of steroid hormone actions that affect brain architecture, molecular and neurochemical processes, behavior and neuroprotection via both genomic and non-genomic actions. Estrogens have such effects throughout the brain and this article provides an historical and current view of how this new view has come about and how it has affected the study of sex differences, as well as other areas of neuroscience, including the effects of stress on the brain.

  20. 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).

  1. 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

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

    PubMed

    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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Experience induces structural and biochemical changes in the adult primate brain.

    PubMed

    Kozorovitskiy, Yevgenia; Gross, Charles G; Kopil, Catherine; Battaglia, Lisa; McBreen, Meghan; Stranahan, Alexis M; Gould, Elizabeth

    2005-11-29

    Primates exhibit complex social and cognitive behavior in the wild. In the laboratory, however, the expression of their behavior is usually limited. A large body of literature shows that living in an enriched environment alters dendrites and synapses in the brains of adult rodents. To date, no studies have investigated the influence of living in a complex environment on brain structure in adult primates. We assessed dendritic architecture, dendritic spines, and synaptic proteins in adult marmosets housed in either a standard laboratory cage or in one of two differentially complex habitats. A month-long stay in either complex environment enhanced the length and complexity of the dendritic tree and increased dendritic spine density and synaptic protein levels in the hippocampus and prefrontal cortex. No differences were detected between the brains of marmosets living in the two differentially complex environments. Our results show that the structure of the adult primate brain remains highly sensitive even to modest levels of experiential complexity. For adult primates, living in standard laboratory housing may induce reversible dendritic spine and synapse decreases in brain regions important for cognition.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. Laterality of mental imagery generation and operation: tests with brain-damaged patients and normal adults.

    PubMed

    Hatta, T; Koike, M; Langman, P

    1994-08-01

    The relationships between hemispheric function and components of the imagery process were examined in patients with unilateral right and left brain damage and in intact adult subjects. In the image generation condition, subjects were required to mentally generate Katakana letters corresponding to Hiragana letters displayed on a CRT. The results for the intact adults suggested a left hemisphere superiority, but the unilaterally brain-damaged subjects showed no hemispheric difference in this task. In the imagery operation task (transformation or lateral translation), subjects were asked to find a genuine Kanji among distractors (pseudo-Kanji) that were constructed from two Kanji radicals (themselves real Kanji) that were either displayed in reverse order or shifted apart. The results for both intact adults and patients with unilateral brain damage suggest the superiority of the right hemisphere. PMID:7525640

  14. The antidepressant tranylcypromine alters cellular proliferation and migration in the adult goldfish brain.

    PubMed

    Romanczyk, Tara B; Jacobowitz, David M; Pollard, Harvey B; Wu, Xingjia; Anders, Juanita J

    2014-10-01

    The goldfish (Carassius auratus) is a widely studied vertebrate model organism for studying cell proliferation in the adult brain, and provide the experimental advantage of growing their body and brain throughout their ∼30-year life time. Cell proliferation occurs in the teleost brain in widespread proliferation zones. Increased cell proliferation in the brain has been linked to the actions of certain antidepressants, including tranylcypromine (TCP), which is used in the treatment of depression. We hypothesized that proliferation zones in the adult goldfish brain can be used to determine the antidepressant effects on cellular proliferation. Here, we report that bromodeoxyuridine (BrdU) labeling over a 24-hr period can be used to rapidly identify the proliferation zones throughout the goldfish brain, including the telencephalon, diencephalon, optic tectal lobes, cerebellum, and facial and vagal lobes. In the first 24 hr of BrdU administration, TCP caused an approximate and significant doubling of labeled cells in the combined brain regions examined, as detected by BrdU immunohistochemistry. TCP caused the greatest increase in cell proliferation in the cerebellum. The normal migratory paths of the proliferating cells within the cerebellum were not affected by TCP treatment. These results indicate that the goldfish provide significant advantages as a vertebrate model for rapidly investigating the effects of antidepressant drugs on cellular proliferation and migration in the normal and injured brain.

  15. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents

    PubMed Central

    Zhou, June; Keenan, Michael J.; Fernandez-Kim, Sun Ok; Pistell, Paul J.; Ingram, Donald K.; Li, Bing; Raggio, Anne M.; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T.; Blackman, Marc R.; Keller, Jeffrey N.; Martin, Roy J.

    2013-01-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (1) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (2) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (3) a higher serum active GLP-1. Third, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (1) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and that (2) GLP-1 is important in the optimal feeding response to a fast. PMID:23818307

  16. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents.

    PubMed

    Zhou, June; Keenan, Michael J; Fernandez-Kim, Sun Ok; Pistell, Paul J; Ingram, Donald K; Li, Bing; Raggio, Anne M; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T; Blackman, Marc R; Keller, Jeffrey N; Martin, Roy J

    2013-11-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast.

  17. Is docosahexaenoic acid synthesis from α-linolenic acid sufficient to supply the adult brain?

    PubMed

    Domenichiello, Anthony F; Kitson, Alex P; Bazinet, Richard P

    2015-07-01

    Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats.

  18. 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

  19. Delineating multiple functions of VEGF-A in the adult brain.

    PubMed

    Licht, Tamar; Keshet, Eli

    2013-05-01

    Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1]. There is a growing body of evidence, however, that VEGF fulfills additional less 'traditional' functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs. This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series. Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach. Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2-4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4-7]. Yet, VEGF continues to be expressed in the adult brain in a constitutive manner. Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions. Here we review current knowledge on some of these 'non-traditional', often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature. These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium). Experimental approaches aimed at distinguishing between these possibilities for each particular

  20. Radial glial cell-specific ablation in the adult Zebrafish brain.

    PubMed

    Shimizu, Yuki; Ito, Yoko; Tanaka, Hideomi; Ohshima, Toshio

    2015-07-01

    The zebrafish brain can continue to produce new neurons in widespread neurogenic brain regions throughout life. In contrast, neurogenesis in the adult mammalian brain is restricted to the subventricular zone (SVZ) and dentate gyrus (DG). In neurogenic regions in the adult brain, radial glial cells (RGCs) are considered to function as neural stem cells (NSCs). We generated a Tg(gfap:Gal4FF) transgenic zebrafish line, which enabled us to express specific genes in RGCs. To study the function of RGCs in neurogenesis in the adult zebrafish brain, we also generated a Tg(gfap: Gal4FF; UAS:nfsB-mcherry) transgenic zebrafish line, which allowed us to induce cell death exclusively within RGCs upon addition of metronidazole (Mtz) to the media. RGCs expressing nitroreductase were specifically ablated by the Mtz treatment, decreasing the number of proliferative RGCs. Using the Tg(gfap:Gal4FF; UAS:nfsB-mcherry) transgenic zebrafish line, we found that RGCs were specifically ablated in the adult zebrafish telencephalon. The Tg(gfap:Gal4FF) line could be useful to study the function of RGCs.

  1. Differential Expression of protocadherin-19, protocadherin-17 and cadherin-6 in Adult Zebrafish Brain

    PubMed Central

    Liu, Qin; Bhattarai, Sunil; Wang, Nan; Sochacka-Marlowe, Alicja

    2015-01-01

    Cell adhesion molecule cadherins play important roles in both development and maintenance of adult structures. Most studies on cadherin expression have been carried out in developing organisms, but information on cadherin distribution in adult vertebrate brains is limited. In this study, we used in situ hybridization to examine mRNA expression of three cadherins, protocadherin-19, protocadherin-17 and cadherin-6 in adult zebrafish brain. Each cadherin exhibits a distinct expression pattern in the fish brain, with protocadherin-19 and protocadherin-17 showing much wider and stronger expression than that of cadherin-6. Both protocadherin-19 and protocadherin-17 expressing cells occur throughout the brain with strong expression in the ventromedial telencephalon, periventricular regions of the thalamus and anterior hypothalamus, stratum periventriculare of the optic tectum, dorsal tegmental nucleus, granular regions of the cerebellar body and valvula, and superficial layers of the facial and vagal lobes. Numerous sensory structures (e.g. auditory, gustatory, lateral line, olfactory and visual nuclei) and motor nuclei (e.g. oculomotor, trochlear, trigeminal motor, abducens and vagal motor nuclei) contain protocadherin-19 and/or protocadherin-17 expressing cell. Expression of these two protocadherins is similar in the ventromedial telencephalon, thalamus, hypothalamus, facial and vagal lobes, but substantially different in the dorsolateral telencephalon, intermediate layers of the optic tectum, and cerebellar valvula. In contrast to the two protocadherins, cadherin-6 expression is much weaker and limited in the adult fish brain. PMID:25612302

  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. Differential expression of protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain.

    PubMed

    Liu, Qin; Bhattarai, Sunil; Wang, Nan; Sochacka-Marlowe, Alicja

    2015-06-15

    Cell adhesion molecule cadherins play important roles in both development and maintenance of adult structures. Most studies on cadherin expression have been carried out in developing organisms, but information on cadherin distribution in adult vertebrate brains is limited. In this study we used in situ hybridization to examine mRNA expression of three cadherins, protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain. Each cadherin exhibits a distinct expression pattern in the fish brain, with protocadherin-19 and protocadherin-17 showing much wider and stronger expression than that of cadherin-6. Both protocadherin-19 and protocadherin-17-expressing cells occur throughout the brain, with strong expression in the ventromedial telencephalon, periventricular regions of the thalamus and anterior hypothalamus, stratum periventriculare of the optic tectum, dorsal tegmental nucleus, granular regions of the cerebellar body and valvula, and superficial layers of the facial and vagal lobes. Numerous sensory structures (e.g., auditory, gustatory, lateral line, olfactory, and visual nuclei) and motor nuclei (e.g., oculomotor, trochlear, trigeminal motor, abducens, and vagal motor nuclei) contain protocadherin-19 and/or protocadherin-17-expressing cell. Expression of these two protocadherins is similar in the ventromedial telencephalon, thalamus, hypothalamus, facial, and vagal lobes, but substantially different in the dorsolateral telencephalon, intermediate layers of the optic tectum, and cerebellar valvula. In contrast to the two protocadherins, cadherin-6 expression is much weaker and limited in the adult fish brain.

  4. Bi-parental care contributes to sexually dimorphic neural cell genesis in the adult mammalian brain.

    PubMed

    Mak, Gloria K; Antle, Michael C; Dyck, Richard H; Weiss, Samuel

    2013-01-01

    Early life events can modulate brain development to produce persistent physiological and behavioural phenotypes that are transmissible across generations. However, whether neural precursor cells are altered by early life events, to produce persistent and transmissible behavioural changes, is unknown. Here, we show that bi-parental care, in early life, increases neural cell genesis in the adult rodent brain in a sexually dimorphic manner. Bi-parentally raised male mice display enhanced adult dentate gyrus neurogenesis, which improves hippocampal neurogenesis-dependent learning and memory. Female mice display enhanced adult white matter oligodendrocyte production, which increases proficiency in bilateral motor coordination and preference for social investigation. Surprisingly, single parent-raised male and female offspring, whose fathers and mothers received bi-parental care, respectively, display a similar enhancement in adult neural cell genesis and phenotypic behaviour. Therefore, neural plasticity and behavioural effects due to bi-parental care persist throughout life and are transmitted to the next generation.

  5. Oligodendrogenesis in the fornix of adult mouse brain; the effect of LPS-induced inflammatory stimulation.

    PubMed

    Fukushima, Shohei; Nishikawa, Kazunori; Furube, Eriko; Muneoka, Shiori; Ono, Katsuhiko; Takebayashi, Hirohide; Miyata, Seiji

    2015-11-19

    Evidence have been accumulated that continuous oligodendrogenesis occurs in the adult mammalian brain. The fornix, projection and commissure pathway of hippocampal neurons, carries signals from the hippocampus to other parts of the brain and has critical role in memory and learning. However, basic characterization of adult oligodendrogenesis in this brain region is not well understood. In the present study, therefore, we aimed to examine the proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) and the effect of acute inflammatory stimulation on oligodendrogenesis in the fornix of adult mouse. We demonstrated the proliferation of OPCs and a new generation of mature oligodendrocytes by using bromodeoxyuridine and Ki67 immunohistochemistry. Oligodendrogenesis of adult fornix was also demonstrated by using oligodendrocyte transcription factor 2 transgenic mouse. A single systemic administration of lipopolysaccharide (LPS) attenuated proliferation of OPCs in the fornix together with reduced proliferation of hippocampal neural stem/progenitor cells. Time course analysis showed that a single administration of LPS attenuated the proliferation of OPCs during 24-48 h. On the other hand, consecutive administration of LPS did not suppress proliferation of OPCs. The treatment of LPS did not affect differentiation of OPCs into mature oligodendrocytes. Treatment of a microglia inhibitor minocycline significantly attenuated basal proliferation of OPCs under normal condition. In conclusion, the present study indicates that continuous oligodendrogenesis occurs and a single administration of LPS transiently attenuates proliferation of OPCs without changing differentiation in the fornix of the adult mouse brains.

  6. 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.

  7. 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

  8. 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…

  9. [Management of swallowing disorders after brain injuries in adults].

    PubMed

    Fichaux, Bourin P; Labrune, M

    2008-01-01

    The management of swallowing disorders after brain injury must be soon as well. The physiopathological analysis and the organization of the therapeutic project of these patients require the intervention of an interdisciplinary team. Dysphagia falls under a complex clinical context associating impairments of cognition, communication and behavioural control. The management associates speech therapist, caregivers, otolaryngolologist, phoniatrician, physiotherapist and nutritional therapist without forgetting the family circle. The fluctuations of consciousness and concentration of our patients brings us to constantly readjusting and rehabilitating the strategies of feeding. Obstacles with their evolution towards a normal feeding are akinesia, limits of motor functions, impairements of cognition and behavioural control. In the located lesions swallow recovers can be fast, instead of in severe brain-injury the challenge is to ensure safe and adequate nutrition, using a variety of strategies depending on the presenting symptoms. The purpose of this article is to relate our experience beside patients with an acute or recent cerbrovascular event.

  10. Enhanced capabilities for imaging gangliosides in murine brain with matrix-assisted laser desorption/ionization and desorption electrospray ionization mass spectrometry coupled to ion mobility separation.

    PubMed

    Škrášková, Karolina; Claude, Emmanuelle; Jones, Emrys A; Towers, Mark; Ellis, Shane R; Heeren, Ron M A

    2016-07-15

    The increased interest in lipidomics calls for improved yet simplified methods of lipid analysis. Over the past two decades, mass spectrometry imaging (MSI) has been established as a powerful technique for the analysis of molecular distribution of a variety of compounds across tissue surfaces. Matrix-assisted laser desorption/ionization (MALDI) MSI is widely used to study the spatial distribution of common lipids. However, a thorough sample preparation and necessity of vacuum for efficient ionization might hamper its use for high-throughput lipid analysis. Desorption electrospray ionization (DESI) is a relatively young MS technique. In DESI, ionization of molecules occurs under ambient conditions, which alleviates sample preparation. Moreover, DESI does not require the application of an external matrix, making the detection of low mass species more feasible due to the lack of chemical matrix background. However, irrespective of the ionization method, the final information obtained during an MSI experiment is very complex and its analysis becomes challenging. It was shown that coupling MSI to ion mobility separation (IMS) simplifies imaging data interpretation. Here we employed DESI and MALDI MSI for a lipidomic analysis of the murine brain using the same IMS-enabled instrument. We report for the first time on the DESI IMS-MSI of multiply sialylated ganglioside species, as well as their acetylated versions, which we detected directly from the murine brain tissue. We show that poly-sialylated gangliosides can be imaged as multiply charged ions using DESI, while they are clearly separated from the rest of the lipid classes based on their charge state using ion mobility. This represents a major improvement in MSI of intact fragile lipid species. We additionally show that complementary lipid information is reached under particular conditions when DESI is compared to MALDI MSI.

  11. 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.

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

    PubMed

    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

    2015-06-16

    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 (SD(BOLD)) 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 SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). 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.

  13. Brain tissue pressure measurements in perinatal and adult rabbits.

    PubMed

    Hornig, G W; Lorenzo, A V; Zavala, L M; Welch, K

    1987-12-01

    Brain tissue pressure (BTP) in pre- and post-natal anesthetized rabbits, held in a stereotactic head holder, was measured with a fluid filled 23 gauge open-ended cannula connected distally to a pressure transducer. By advancing the cannula step wise through a hole in the cranium it was possible to sequentially measure pressure from the cranial subarachnoid space, cortex, ventricle and basal ganglia. Separate cannulas and transducers were used to measure CSFP from the cisterna magna and arterial and/or venous pressure. Pressure recordings obtained when the tip of the BTP cannula was located in the cranial subarachnoid space or ventricle exhibited respiratory and blood pressure pulsations equivalent to and in phase with CSF pulsations recorded from the cisterna magna. When the tip was advanced into brain parenchymal sites such pulsations were suppressed or non-detectable unless communication with a CSF compartment had been established inadvertently. Although CSF pressures in the three spinal fluid compartments were equivalent, in most animals BTP was higher than CSFP. However, after momentary venting of the system BTP equilibrated at a pressure below that of CSFP. We speculate that venting of the low compliance system (1.20 x 10(-5) ml/mmHg) relieves the isometric pressure build-up due to insertion of the cannula into brain parenchyma. Under these conditions, and at all ages examined, BTP in the rabbit is consistently lower than CSFP and, as with CSFP, it increases as the animal matures.

  14. 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

  15. Minimal Brain Dysfunction in Childhood: 1. Outcome in Late Adolescence and Early Adult Years. Final Version.

    ERIC Educational Resources Information Center

    Milman, Doris H.

    Seventy-three patients, diagnosed in childhood as having either maturational lag or organic brain syndrome, were followed for an average of 12 years into late adolescence and early adult life for the purpose of discovering the outcome with respect to ultimate psychiatric status, educational attainment, social adjustment, and global adjustment. At…

  16. 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)

  17. 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…

  18. Radial glia-like cells persist in the adult rat brain.

    PubMed

    Gubert, Fernanda; Zaverucha-do-Valle, Camila; Pimentel-Coelho, Pedro M; Mendez-Otero, Rosalia; Santiago, Marcelo F

    2009-03-01

    During development, radial glia cells contribute to neuronal migration and neurogenesis, and differentiate into astrocytes by the end of the developmental period. Recently, it was demonstrated that during development, radial glia cells, in addition to their role in migration, also give rise to neuroblasts. Furthermore, radial glial cells remain in the adult brain as adult neural stem cells (NSC) in the subventricular zone (SVZ) around the lateral ventricles (LVs), and generate new neurons continuously throughout adulthood. In this study, we used immunohistochemical and morphological methods to investigate the presence of radial glia-like cells around the LVs during the postnatal development period until adulthood in rats. In all ages of rats studied, we identified cells with morphological and immunocytochemical features that are similar to the radial glia cells found in the embryonic brain. Similarly to the radial glia, these cells express nestin and vimentin, and have a radial morphology, extending perpendicularly as processes from the ventricle wall. These cells also express GFAP, GLAST, and Pax6, and proliferate. In the brains of adult rats, we identified cells with relatively long processes (up to 600 mum) in close apposition with migrating neuroblasts. Our results showed that the radial glia-like cells present in the adult rat brain share several morphological and functional characteristics with the embryonic radial glia. We suggest that the embryonic radial glia cells located around the LV walls do not complete their transformation into astrocytes, but rather persist in adulthood.

  19. Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain

    PubMed Central

    Duan, Xin; Chang, Jay H.; Ge, Shaoyu; Faulkner, Regina L.; Kim, Ju Young; Kitabatake, Yasuji; Liu, Xiao-bo; Yang, Chih-Hao; Jordan, J. Dedrick; Ma, Dengke K.; Liu, Cindy Y.; Ganesan, Sundar; Cheng, Hwai-Jong; Ming, Guo-li; Lu, Bai; Song, Hongjun

    2007-01-01

    Summary Adult neurogenesis occurs throughout life in discrete regions of the adult mammalian brain. Little is known about the mechanism governing the sequential developmental process that leads to integration of new neurons from adult neural stem cells into the existing circuitry. Here, we investigated roles of Disrupted-In-Schizophrenia 1 (DISC1), a schizophrenia susceptibility gene, in adult hippocampal neurogenesis. Unexpectedly, down regulation of DISC1 leads to accelerated neuronal integration, resulting in aberrant morphological development and mis-positioning of new dentate granule cells in a cell-autonomous fashion. Functionally, newborn neurons with DISC1 knockdown exhibit enhanced excitability and accelerated dendritic development and synapse formation. Furthermore, DISC1 cooperates with its binding partner Ndel1 in regulating adult neurogenesis. Taken together, our study identifies DISC1 as a key regulator that orchestrates the tempo of functional neuronal integration in the adult brain and demonstrates essential roles of a susceptibility gene for major mental illness in neuronal development, including adult neurogenesis. PMID:17825401

  20. [Specific features of rhino-sinusogenic brain abscesses in adults and children].

    PubMed

    Blagoveshchenskaia, N S; Mukhamedzhanov, N Z

    1989-01-01

    Analysis of observations of 49 patients with rhinosinusogenic brain abscesses revealed differences in their development between adults and children. This pathology occurs in adults more frequently than in children, particularly young children. In adults, brain abscesses usually develop as a result of chronic frontal- or polysinusitis, while in children they typically occur after maxillary sinusitis and in early age children also after acute suppuration in the nasal cavity. For adults, the contact pathway of infection is characteristic, whereas for children, the hematogenic-metastatic pathway is typical. Adults show single abscesses while children show both single, multiple and multichamber abscesses accompanied by separation of cranial sutures, thinning of calvaria, and protrusion and tension of the cranial fontanel. In children, abscesses may grow very large. In adults, the hypertensive syndrome is very distinct, while in children, the hydrocephalic-hypertensive syndrome comes to the foreground. In children, infectious-toxic symptoms are more significant. In adults, focal neurological symptoms become more serious than in children in whom they are also more labile.

  1. Structural brain correlates of associative memory in older adults.

    PubMed

    Becker, Nina; Laukka, Erika J; Kalpouzos, Grégoria; Naveh-Benjamin, Moshe; Bäckman, Lars; Brehmer, Yvonne

    2015-09-01

    Associative memory involves binding two or more items into a coherent memory episode. Relative to memory for single items, associative memory declines greatly in aging. However, older individuals vary substantially in their ability to memorize associative information. Although functional studies link associative memory to the medial temporal lobe (MTL) and prefrontal cortex (PFC), little is known about how volumetric differences in MTL and PFC might contribute to individual differences in associative memory. We investigated regional gray-matter volumes related to individual differences in associative memory in a sample of healthy older adults (n=54; age=60years). To differentiate item from associative memory, participants intentionally learned face-scene picture pairs before performing a recognition task that included single faces, scenes, and face-scene pairs. Gray-matter volumes were analyzed using voxel-based morphometry region-of-interest (ROI) analyses. To examine volumetric differences specifically for associative memory, item memory was controlled for in the analyses. Behavioral results revealed large variability in associative memory that mainly originated from differences in false-alarm rates. Moreover, associative memory was independent of individuals' ability to remember single items. Older adults with better associative memory showed larger gray-matter volumes primarily in regions of the left and right lateral PFC. These findings provide evidence for the importance of PFC in intentional learning of associations, likely because of its involvement in organizational and strategic processes that distinguish older adults with good from those with poor associative memory.

  2. 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

  3. Environment matters: synaptic properties of neurons born in the epileptic adult brain develop to reduce excitability.

    PubMed

    Jakubs, Katherine; Nanobashvili, Avtandil; Bonde, Sara; Ekdahl, Christine T; Kokaia, Zaal; Kokaia, Merab; Lindvall, Olle

    2006-12-21

    Neural progenitors in the adult dentate gyrus continuously produce new functional granule cells. Here we used whole-cell patch-clamp recordings to explore whether a pathological environment influences synaptic properties of new granule cells labeled with a GFP-retroviral vector. Rats were exposed to a physiological stimulus, i.e., running, or a brain insult, i.e., status epilepticus, which gave rise to neuronal death, inflammation, and chronic seizures. Granule cells formed after these stimuli exhibited similar intrinsic membrane properties. However, the new neurons born into the pathological environment differed with respect to synaptic drive and short-term plasticity of both excitatory and inhibitory afferents. The new granule cells formed in the epileptic brain exhibited functional connectivity consistent with reduced excitability. We demonstrate a high degree of plasticity in synaptic inputs to adult-born new neurons, which could act to mitigate pathological brain function.

  4. 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

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

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-12-31

    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.

  6. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  7. Transcriptional Profiling of Adult Neural Stem-Like Cells from the Human Brain

    PubMed Central

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O.; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A.

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33–60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate. PMID

  8. 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

  9. 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.

  10. 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

  11. Regional distribution of neuropeptide processing endopeptidases in adult rat brain.

    PubMed

    Berman, Y L; Rattan, A K; Carr, K; Devi, L

    1994-01-01

    Many peptide hormone and neuropeptide precursors undergo post-translational processing at mono- and/or dibasic residues. An enzymatic activity capable of processing prodynorphin at a monobasic processing site designated 'dynorphin converting enzyme' has been previously reported in rat rain and bovine pituitary. In this study the distribution of dynorphin converting enzyme activity in ten regions of rat brain has been compared with the distribution of subtilisin-like processing enzymes and with the immuno-reactive dynorphin peptides. The distribution of dynorphin converting enzyme activity generally matches the distribution of immuno-reactive dynorphin B-13 in most but not all brain regions. The regions that are known to have a relatively large number of immuno-reactive dynorphin-neurons also contain high levels of dynorphin converting enzyme activity. The distribution of dynorphin converting enzyme activity does not match the distribution of subtilisin-like processing enzyme or carboxypeptidase E activities. Taken together the data support the possibility that the dynorphin converting enzyme is involved in the maturation of dynorphin, as well as other neuropeptides, and peptide hormones.

  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. Neuronal replacement from endogenous precursors in the adult brain after stroke.

    PubMed

    Arvidsson, Andreas; Collin, Tove; Kirik, Deniz; Kokaia, Zaal; Lindvall, Olle

    2002-09-01

    In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans. PMID:12161747

  15. Laboratory investigations on neuroparalytic accidents associated with suckling mouse brain rabies vaccine. III. -- Preservation of vaccine potency after elimination of murine brain myelin by centrifugation.

    PubMed

    Larghi, O P; Varela-Diaz, V M; Soto, E; Imas, B; Cuba-Caparo, A; Fuenzalida, E

    1976-01-01

    Myelin, which has been found in nine day-old mouse brain, was eliminated from weanling mouse brain suspensions by centrifugation at 17,000 g for 10 min, as demonstrated by electron microscopy and guinea-pig inoculation tests for encephalitogenic activity. This centrifugation procedure did not affect the potency of seven batches of suckling mouse brain vaccine, when centrifuged and non-centrifuged samples of the same batches were compared by a modified NIH potency test (t = 0.17). The present results with weanling mouse brain preparations suggest that centrifugation at 17,000 g be used in the preparation of rabies suckling mouse brain vaccine instead of the 1,900 g currently employed, which does not eliminate myelin. This new procedure would be expected to reduce the number of postvaccinal reactions which are attributable to the small amount of myelin which remains in vaccines prepared with new-born animal brains following the current procedure.

  16. 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

  17. 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

  18. 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

  19. Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain.

    PubMed

    Alfonso-Loeches, Silvia; Guerri, Consuelo

    2011-01-01

    The brain is one of the major target organs of alcohol actions. Alcohol abuse can lead to alterations in brain structure and functions and, in some cases, to neurodegeneration. Cognitive deficits and alcohol dependence are highly damaging consequences of alcohol abuse. Clinical and experimental studies have demonstrated that the developing brain is particularly vulnerable to alcohol, and that drinking during gestation can lead to a range of physical, learning and behavioral defects (fetal alcohol spectrum disorders), with the most dramatic presentation corresponding to fetal alcohol syndrome. Recent findings also indicate that adolescence is a stage of brain maturation and that heavy drinking at this stage can have a negative impact on brain structure and functions causing important short- and long-term cognitive and behavioral consequences. The effects of alcohol on the brain are not uniform; some brain areas or cell populations are more vulnerable than others. The prefrontal cortex, the hippocampus, the cerebellum, the white matter and glial cells are particularly susceptible to the effects of ethanol. The molecular actions of alcohol on the brain are complex and involve numerous mechanisms and signaling pathways. Some of the mechanisms involved are common for the adult brain and for the developing brain, while others depend on the developmental stage. During brain ontogeny, alcohol causes irreversible alterations to the brain structure. It also impairs several molecular, neurochemical and cellular events taking place during normal brain development, including alterations in both gene expression regulation and the molecules involved in cell-cell interactions, interference with the mitogenic and growth factor response, enhancement of free radical formation and derangements of glial cell functions. However, in both adult and adolescent brains, alcohol damages specific brain areas through mechanisms involving excitotoxicity, free radical formation and

  20. Homeostasis of Microglia in the Adult Brain: Review of Novel Microglia Depletion Systems.

    PubMed

    Waisman, Ari; Ginhoux, Florent; Greter, Melanie; Bruttger, Julia

    2015-10-01

    Microglia are brain macrophages that emerge from early erythro-myeloid precursors in the embryonic yolk sac and migrate to the brain mesenchyme before the blood brain barrier is formed. They seed the brain, and proliferate until they have formed a grid-like distribution in the central nervous system that is maintained throughout lifespan. The mechanisms through which these embryonic-derived cells contribute to microglia homoeostasis at steady state and upon inflammation are still not entirely clear. Here we review recent studies that provided insight into the contribution of embryonically-derived microglia and of adult 'microglia-like' cells derived from monocytes during inflammation. We examine different microglia depletion models, and discuss the origin of their rapid repopulation after depletion and outline important areas of future research.

  1. The needs of aging parents caring for an adult with acquired brain injury.

    PubMed

    Minnes, Patricia; Woodford, Lynn; Carlson, Peter; Johnston, Jane; McColl, Mary Ann

    2010-06-01

    This study focused on issues of concern to and service needs of older parents caring for an adult son or daughter with an acquired brain injury (ABI) in Ontario. Three issues were identified as particularly challenging: diagnosis of the brain injury, parents' feelings about the cause of the brain injury, and planning for long-term accommodation for their family member with a brain injury. The most frequently cited services needed for the person with ABI were social and/or recreational activities, day programs, and residential placement. The most frequently cited services needed by parents were parent education and support groups. The information gathered provides a base for further research in other sectors. Implications of these initial findings for clinical practice and policy and program development are discussed.

  2. Analysis of chaperone mRNA expression in the adult mouse brain by meta analysis of the Allen Brain Atlas.

    PubMed

    Tebbenkamp, Andrew T N; Borchelt, David R

    2010-10-28

    The pathology of many neurodegenerative diseases is characterized by the accumulation of misfolded and aggregated proteins in various cell types and regional substructures throughout the central and peripheral nervous systems. The accumulation of these aggregated proteins signals dysfunction of cellular protein homeostatic mechanisms such as the ubiquitin/proteasome system, autophagy, and the chaperone network. Although there are several published studies in which transcriptional profiling has been used to examine gene expression in various tissues, including tissues of neurodegenerative disease models, there has not been a report that focuses exclusively on expression of the chaperone network. In the present study, we used the Allen Brain Atlas online database to analyze chaperone expression levels. This database utilizes a quantitative in situ hybridization approach and provides data on 270 chaperone genes within many substructures of the adult mouse brain. We determined that 256 of these chaperone genes are expressed at some level. Surprisingly, relatively few genes, only 30, showed significant variations in levels of mRNA across different substructures of the brain. The greatest degree of variability was exhibited by genes of the DnaJ co-chaperone, Tetratricopeptide repeat, and the HSPH families. Our analysis provides a valuable resource towards determining how variations in chaperone gene expression may modulate the vulnerability of specific neuronal populations of mammalian brain.

  3. 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.…

  4. 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

  5. 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

  6. 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.

  7. 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

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

    PubMed

    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

    2015-01-01

    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

  9. Light scattering properties vary across different regions of the adult mouse brain.

    PubMed

    Al-Juboori, Saif I; Dondzillo, Anna; Stubblefield, Elizabeth A; Felsen, Gidon; Lei, Tim C; Klug, Achim

    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.

  10. 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

  11. Prenatal exposure to permethrin influences vascular development of fetal brain and adult behavior in mice offspring.

    PubMed

    Imanishi, Satoshi; Okura, Masahiro; Zaha, Hiroko; Yamamoto, Toshifumi; Akanuma, Hiromi; Nagano, Reiko; Shiraishi, Hiroaki; Fujimaki, Hidekazu; Sone, Hideko

    2013-11-01

    Pyrethroids are one of the most widely used classes of insecticides and show neurotoxic effects that induce oxidative stress in the neonatal rat brain. However, little is still known about effects of prenatal exposure to permethrin on vascular development in fetal brain, central nervous system development, and adult offspring behaviors. In this study, the effects of prenatal exposure to permethrin on the development of cerebral arteries in fetal brains, neurotransmitter in neonatal brains, and locomotor activities in offspring mice were investigated. Permethrin (0, 2, 10, 50, and 75 mg/kg) was orally administered to pregnant females once on gestation day 10.5. The brains of permethrin-treated fetuses showed altered vascular formation involving shortened lengths of vessels, an increased number of small branches, and, in some cases, insufficient fusion of the anterior communicating arteries in the area of circle of Willis. The prenatal exposure to permethrin altered neocortical and hippocampus thickness in the mid brain and significantly increased norepinephrine and dopamine levels at postnatal day 7 mice. For spontaneous behavior, the standing ability test using a viewing jar and open-field tests showed significant decrease of the standing ability and locomotor activity in male mice at 8 or 12 weeks of age, respectively. The results suggest that prenatal exposure to permethrin may affect insufficient development of the brain through alterations of vascular development.

  12. Light scattering properties vary across different regions of the adult mouse brain

    NASA Astrophysics Data System (ADS)

    Al-Juboori, Saif I.

    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.

  13. MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults.

    PubMed

    Wefers, Benedikt; Hitz, Christiane; Hölter, Sabine M; Trümbach, Dietrich; Hansen, Jens; Weber, Peter; Pütz, Benno; Deussing, Jan M; de Angelis, Martin Hrabé; Roenneberg, Till; Zheng, Fang; Alzheimer, Christian; Silva, Alcino; Wurst, Wolfgang; Kühn, Ralf

    2012-01-01

    MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype.Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as a new valuable approach, allowing it to discriminate between gene function in the adult and the developing postnatal brain. PMID:22529971

  14. Area-specific migration and recruitment of new neurons in the adult songbird brain.

    PubMed

    Vellema, Michiel; van der Linden, Annemie; Gahr, Manfred

    2010-05-01

    Neuron recruitment has been implicated in morphological and functional plasticity in the adult brain. Whereas mammals restrict neuron recruitment specifically to two regions of known plasticity, the hippocampus and olfactory bulb, newborn neurons are found throughout the forebrain of adult songbirds. In order to study the area-specificity of the widespread proliferation and recruitment in the songbird brain, six adult male canaries received repetitive intraperitoneal injections of the mitotic marker BrdU (5-bromo-2-deoxyuridine) and were sacrificed after 24 hours to study proliferation or after 38 days to study recruitment. Migration and incorporation of new neurons was apparent throughout many but not all parts of the canary forebrain and was quantitatively related to mitotic levels in the most closely associated proliferative zones. Surprisingly, some areas of the vocal control system sensitive to plastic changes, such as nucleus higher vocal center (HVC) and area X, recruited similar numbers of new neurons as their surrounding brain tissues, employing no specific directional mechanisms. The distribution pattern in and around HVC could best be described by a random displacement model, where cells originating from the overlying lateral ventricle can move independently in any direction. Other plastic song control areas, such as the medial magnocellular nucleus of anterior nidopallium and the robust nucleus of arcopallium, were specifically avoided by migrating neurons, while migration toward the olfactory bulb showed high specificity, similar to the mammalian rostral migratory stream. Thus, different mechanisms appear to organize area-specific neuron recruitment in different recipients of the adult songbird brain, unrelated to global plasticity of brain regions.

  15. 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

  16. Effects of exogenous, nonleukemogenic, ecotropic murine leukemia virus infections on the immune systems of adult C57BL/6 mice.

    PubMed Central

    Lee, J S; Giese, N A; Elkins, K L; Yetter, R A; Holmes, K L; Hartley, J W; Morse, H C

    1995-01-01

    Mouse AIDS (MAIDS) develops in mice infected with a mixture of replication-competent ecotropic and mink lung cell focus-inducing murine leukemia viruses and an etiologic replication-defective virus. Helper viruses are not required for induction of MAIDS, but the time course of disease is accelerated in their presence. To understand the possible contributions of ectropic murine leukemia viruses to MAIDS pathogenesis, we biologically cloned a series of viruses from the MAIDS-inducing LP-BM5 virus mixture. These viruses were examined for replication in tissues of infected mice and for effects on the immune system. All virus stocks replicated efficiently in mice. Infected animals showed slight lymphadenopathy and splenomegaly due primarily to B-cell proliferation associated with differentiation to immunoglobulin secretion resulting in twofold increases in serum immunoglobulin M levels; however, B-cell responses to helper T-cell-independent antigens were increased rather than decreased as in MAIDS. Analyses of CD8+ T-cell function showed that cytotoxic T-lymphocyte responses to alloantigens were comparable in control and infected mice. Finally, we showed that infection resulted in enhanced expression of transcripts for interleukin-10, interleukin-4, and gamma interferon. These cytokines can all contribute to B-cell activation and may promote the expansion of a target cell population for the MAIDS defective virus. PMID:7769677

  17. Reorganization and plasticity in the adult brain during learning of motor skills.

    PubMed

    Doyon, Julien; Benali, Habib

    2005-04-01

    On the basis of brain imaging studies, Doyon and Ungerleider recently proposed a model describing the cerebral plasticity that occurs in both cortico-striatal and cortico-cerebellar systems of the adult brain during learning of new motor skilled behaviors. This theoretical framework makes several testable predictions with regards to the contribution of these neural systems based on the phase (fast, slow, consolidation, automatization, and retention) and nature of the motor learning processes (motor sequence versus motor adaptation) acquired through repeated practice. There has been recent behavioral, lesion and additional neuroimaging studies that have addressed the assumptions made in this theory that will help in the revision of this model.

  18. Brain lesions that impair vocal imitation in adult budgerigars.

    PubMed

    Plummer, Thane K; Striedter, Georg F

    2002-11-15

    Vocal imitation is a complex form of imitative learning that is well developed only in humans, dolphins, and birds. Among birds, only some species are able to imitate sounds in adulthood. Of these, the budgerigar (Melopsittacus undulatus) has been studied in most detail. Previous studies suggested that the vocal motor system in budgerigars receives auditory information from the lateral frontal neostriatum (NFl). In the present study, we confirm this hypothesis by showing that infusions of the GABA agonist muscimol into NFl reduce the strength of auditory responses in a telencephalic vocal motor nucleus, the central nucleus of the lateral neostriatum (NLc). To test whether the auditory information conveyed from NFl to NLc plays a role in vocal imitation, we lesioned parts of NFl and the overlying ventral hyperstriatum (HVl) in seven adult male budgerigars and then examined whether the lesioned males would imitate the calls of females with whom they were paired. We found that, compared to sham-lesioned controls, the lesioned birds were significantly impaired in their imitation of female calls. Yet, the lesioned males were clearly not deaf (e.g., their previously learned calls did not degrade as they do after deafening). Therefore, the data suggest that NFl/HVl lesions impair vocal imitation by reducing the amount of auditory information that reaches the vocal motor system. Interestingly, the females that were paired with lesioned males displayed more vocal plasticity than the females in the control group, and some even imitated their male's prepairing calls.

  19. 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

  20. [Detection of the generation of nitric oxide from L-arginine in the murine brain in vivo using EPR].

    PubMed

    Mikoian, V D; Kubrina, L N; Vanin, A F

    1994-01-01

    Nitric oxide (NO) was shown by EPR method to be generated via L-arginine-dependent way in brain of mice in vivo. The complexes of diethyldithiocarbamate (DETC) or pirrolidinedithiocarbamate (PDTC) with endogenous or exogenous Fe2+ were used as a traps of NO, which are capable to bind NO resulted in the formation of mononitrosyl iron complexes with DETC or PDTC (MNIC-DETC or PDTC) recovered by EPR method. These complexes were detected in mouse brain in concentration of 2.5 nmole/g of wet tissue for 30 min only when exogenous Fe2+ was injected in to mice. The level of MNIC-DETC (PDTC) was 5 fold increased in brain of mice pretreated for 4 hrs with lipopolysaccharide from Escherichia coli, which induced the inflammation processes. The inhibitor of NO-synthase, NG-nitro-L-arginine attenuated the formation of MNIC-DETC (PDTC) in mouse brain in vivo. Exogenous Fe2+ is suggested to induced the synthesis of NO-synthase in mouse brain. PMID:7529563

  1. Single episode of mild murine malaria induces neuroinflammation, alters microglial profile, impairs adult neurogenesis, and causes deficits in social and anxiety-like behavior.

    PubMed

    Guha, Suman K; Tillu, Rucha; Sood, Ankit; Patgaonkar, Mandar; Nanavaty, Ishira N; Sengupta, Arjun; Sharma, Shobhona; Vaidya, Vidita A; Pathak, Sulabha

    2014-11-01

    Cerebral malaria is associated with cerebrovascular damage and neurological sequelae. However, the neurological consequences of uncomplicated malaria, the most prevalent form of the disease, remain uninvestigated. Here, using a mild malaria model, we show that a single Plasmodium chabaudi adami infection in adult mice induces neuroinflammation, neurogenic, and behavioral changes in the absence of a blood-brain barrier breach. Using cytokine arrays we show that the infection induces differential serum and brain cytokine profiles, both at peak parasitemia and 15days post-parasite clearance. At the peak of infection, along with the serum, the brain also exhibited a definitive pro-inflammatory cytokine profile, and gene expression analysis revealed that pro-inflammatory cytokines were also produced locally in the hippocampus, an adult neurogenic niche. Hippocampal microglia numbers were enhanced, and we noted a shift to an activated profile at this time point, accompanied by a striking redistribution of the microglia to the subgranular zone adjacent to hippocampal neuronal progenitors. In the hippocampus, a distinct decline in progenitor turnover and survival was observed at peak parasitemia, accompanied by a shift from neuronal to glial fate specification. Studies in transgenic Nestin-GFP reporter mice demonstrated a decline in the Nestin-GFP(+)/GFAP(+) quiescent neural stem cell pool at peak parasitemia. Although these cellular changes reverted to normal 15days post-parasite clearance, specific brain cytokines continued to exhibit dysregulation. Behavioral analysis revealed selective deficits in social and anxiety-like behaviors, with no change observed in locomotor, cognitive, and depression-like behaviors, with a return to baseline at recovery. Collectively, these findings indicate that even a single episode of mild malaria results in alterations of the brain cytokine profile, causes specific behavioral dysfunction, is accompanied by hippocampal microglial

  2. Pheromone-induced cell proliferation in the murine subventricular zone.

    PubMed

    Koyama, Sachiko; Soini, Helena A; Foley, John; Novotny, Milos V; Lai, Cary

    2014-08-01

    Enhancement of adult neurogenesis in female mice was previously demonstrated through exposure to soiled bedding from males, although the identity of relevant chemosignals has remained unknown. The farnesenes and SBT (2-sec-butyl-4,5-dihydrothiazole) are male murine pheromones that dominant males secrete at higher levels. Previous studies have shown that they induce oestrus in female mice. We have recently shown that these pheromones strongly increase cell proliferation in the SVZ (subventricular zone) of adult female mice. In addition, we found that a female murine pheromone, 2,5-dimethylpyrazine, facilitates similar changes in males. 2,5-dimethylpyrazine is a female pheromone that is secreted when females are housed in large groups and it was originally found to suppress oestrus in females. We found that it does not have suppressive effect on the cell proliferation in the SVZ of females. Similarly, male murine pheromones, SBT and the farnesenes, do not show a suppressive effect on the cell proliferation in the SVZ of males. Our results demonstrated that pheromonal communication between males and females has strong stimulatory effect on both the reproductive physiology and brain cell proliferation, but intrasex pheromonal exchanges do not reduce progenitor proliferation in these brain regions.

  3. 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

  4. Regulation of stroke-induced neurogenesis in adult brain--recent scientific progress.

    PubMed

    Kokaia, Zaal; Thored, Pär; Arvidsson, Andreas; Lindvall, Olle

    2006-07-01

    Stroke induced by middle cerebral artery occlusion in adult rodents induces the formation of new neurons in the damaged striatum, a region that normally does not show neurogenesis. Here we describe recent findings on the regulation of neurogenesis after stroke, in particular regarding the duration of the neurogenic response and the influence of age, as well as the molecular mechanisms influencing migration and survival of the new neurons. We also discuss some crucial issues that need to be addressed in the further exploration of this potential self-repair mechanism after damage to the adult brain. PMID:16766702

  5. Magnetic resonance imaging (MRI) detection of the murine brain response to light: Temporal differentiation and negative functional MRI changes

    SciTech Connect

    Huang, Wei ||; Palyka, I. |; Li, HaiFang

    1996-06-11

    Using a 9.4 T MRI instrument, we have obtained images of the mouse brain response to photic stimulation during a period between deep anesthesia and the early stages of arousal. The large image enhancements we observe (often >30%) are consistent with literature results extrapolated to 9.4 T. However, there are also two unusual aspects to our findings. (i) The visual area of the brain responds only to changes in stimulus intensity, suggesting that we directly detect operations of the M visual system pathway. Such a channel has been observed in mice by invasive electrophysiology, and described in detail for primates. (ii) Along with the typical positive response in the area of the occipital portion of the brain containing the visual cortex; another area displays decreased signal intensity upon stimulation. 41 refs., 4 figs.

  6. 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.

  7. 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

  8. Environmental impact on direct neuronal reprogramming in vivo in the adult brain.

    PubMed

    Grande, Andrew; Sumiyoshi, Kyoko; 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 the 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 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 Neurogenin2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischaemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo.

  9. Role of astrocytes as neural stem cells in the adult brain

    PubMed Central

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo

    2012-01-01

    In the adult mammalian brain, bona fide neural stem cells were discovered in the subventricular zone (SVZ), the largest neurogenic niche lining the striatal wall of the lateral ventricles of the brain. In this region resides a subpopulation of astrocytes that express the glial fibrillary acidic protein (GFAP), nestin and LeX. Astonishingly, these GFAP-expressing progenitors display stem-cell-like features both in vivo and in vitro. Throughout life SVZ astrocytes give rise to interneurons and oligodendrocyte precursors, which populate the olfactory bulb and the white matter, respectively. The role of the progenies of SVZ astrocytes has not been fully elucidated, but some evidence indicates that the new neurons play a role in olfactory discrimination, whereas oligodendrocytes contribute to myelinate white matter tracts. In this chapter, we describe the astrocytic nature of adult neural stem cells, their organization into the SVZ and some of their molecular and genetic characteristics. PMID:23619383

  10. 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

  11. Radiation-Induced Alteration of the Brain Proteome: Understanding the Role of the Sirtuin 2 Deacetylase in a Murine Model

    PubMed Central

    2015-01-01

    Whole brain radiotherapy (WBRT) produces unwanted sequelae, albeit via unknown mechanisms. A deacetylase expressed in the central nervous system, Sirtuin 2 (SIRT2), has been linked to neurodegeneration. Therefore, we sought to challenge the notion that a single disease pathway is responsible for radiation-induced brain injury in Sirt2 wild-type (WT) and knockout (KO) mice at the proteomic level. We utilized isobaric tag for relative and absolute quantitation to analyze brain homogenates from Sirt2 WT and KO mice with and without WBRT. Selected proteins were independently verified, followed by ingenuity pathway analysis. Canonical pathways for Huntington’s, Parkinson’s, and Alzheimer’s were acutely affected by radiation within 72 h of treatment. Although loss of Sirt2 preferentially affected both Huntington’s and Parkinson’s pathways, WBRT most significantly affected Huntington’s-related proteins in the absence of Sirt2. Identical protein expression patterns were identified in Mog following WBRT in both Sirt2 WT and KO mice, revealing a proteomic radiation signature; however, long-term radiation effects were found to be associated with altered levels of a small number of key neurodegeneration-related proteins, identified as Mapt, Mog, Snap25, and Dnm1. Together, these data demonstrate the principle that the presence of Sirt2 can have significant effects on the brain proteome and its response to ionizing radiation. PMID:26373435

  12. 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

  13. Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells

    PubMed Central

    Shivraj Sohur, U; Emsley, Jason G; Mitchell, Bartley D; Macklis, Jeffrey D

    2006-01-01

    Recent work in neuroscience has shown that the adult central nervous system (CNS) contains neural progenitors, precursors and stem cells that are capable of generating new neurons, astrocytes and oligodendrocytes. While challenging the previous dogma that no new neurons are born in the adult mammalian CNS, these findings bring with them the future possibilities for development of novel neural repair strategies. The purpose of this review is to present the current knowledge about constitutively occurring adult mammalian neurogenesis, highlight the critical differences between ‘neurogenic’ and ‘non-neurogenic’ regions in the adult brain, and describe the cardinal features of two well-described neurogenic regions—the subventricular zone/olfactory bulb system and the dentate gyrus of the hippocampus. We also provide an overview of presently used models for studying neural precursors in vitro, mention some precursor transplantation models and emphasize that, in this rapidly growing field of neuroscience, one must be cautious with respect to a variety of methodological considerations for studying neural precursor cells both in vitro and in vivo. The possibility of repairing neural circuitry by manipulating neurogenesis is an intriguing one, and, therefore, we also review recent efforts to understand the conditions under which neurogenesis can be induced in non-neurogenic regions of the adult CNS. This work aims towards molecular and cellular manipulation of endogenous neural precursors in situ, without transplantation. We conclude this review with a discussion of what might be the function of newly generated neurons in the adult brain, and provide a summary of present thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease. PMID:16939970

  14. 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

  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. Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults.

    PubMed

    Tarumi, Takashi; de Jong, Daan L K; Zhu, David C; Tseng, Benjamin Y; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B; Kerwin, Diana R; Lu, Hanzhang; Munro Cullum, C; Zhang, Rong

    2015-04-15

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65 ± 6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

  17. Optimized heterologous transfection of viable adult organotypic brain slices using an enhanced gene gun

    PubMed Central

    2013-01-01

    Background Organotypic brain slices (OTBS) are an excellent experimental compromise between the facility of working with cell cultures and the biological relevance of using animal models where anatomical, morphological, and cellular function of specific brain regions can be maintained. The biological characteristics of OTBS can subsequently be examined under well-defined conditions. They do, however, have a number of limitations; most brain slices are derived from neonatal animals, as it is difficult to properly prepare and maintain adult OTBS. There are ample problems with tissue integrity as OTBS are delicate and frequently become damaged during the preparative stages. Notwithstanding these obstacles, the introduced exogenous proteins into both neuronal cells, and cells imbedded within tissues, have been consistently difficult to achieve. Results Following the ex vivo extraction of adult mouse brains, mounted inside a medium-agarose matrix, we have exploited a precise slicing procedure using a custom built vibroslicer. To transfect these slices we used an improved biolistic transfection method using a custom made low-pressure barrel and novel DNA-coated nanoparticles (40 nm), which are drastically smaller than traditional microparticles. These nanoparticles also minimize tissue damage as seen by a significant reduction in lactate dehydrogenase activity as well as propidium iodide (PI) and dUTP labelling compared to larger traditional gold particles used on these OTBS. Furthermore, following EYFP exogene delivery by gene gun, the 40 nm treated OTBS displayed a significantly larger number of viable NeuN and EYFP positive cells. These OTBS expressed the exogenous proteins for many weeks. Conclusions Our described methodology of producing OTBS, which results in better reproducibility with less tissue damage, permits the exploitation of mature fully formed adult brains for advanced neurobiological studies. The novel 40 nm particles are ideal for the viable

  18. 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.

  19. 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

  20. 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

  1. Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

    PubMed

    Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

    2015-03-01

    This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at <33 weeks of gestation. Structural brain correlates and risk factors at birth, in childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Landmark-based morphometrics of the normal adult brain using MRI.

    PubMed

    Free, S L; O'Higgins, P; Maudgil, D D; Dryden, I L; Lemieux, L; Fish, D R; Shorvon, S D

    2001-05-01

    We describe the application of statistical shape analysis to homologous landmarks on the cortical surface of the adult human brain. Statistical shape analysis has a sound theoretical basis. Landmarks are identified on the surface of a 3-D reconstruction of the segmented cortical surface from magnetic resonance image (MRI) data. Using publicly available software (morphologika) the location and size dependence of the landmarks are removed and the differences in landmark distribution across subjects are analysed using principal component analysis. These differences, representing shape differences between subjects, can be visually assessed using wireframe models and transformation grids. The MRI data of 58 adult brains (27 female and 15 left handed) were examined. Shape differences in the whole brain are described which concern the relative orientation of frontal lobe sulci. Analysis of all 116 hemispheres revealed a statistically significant difference (P < 0.001) between left and right hemispheres. This finding was significant for right- but not left-handed subjects alone. No other significant age, gender, handedness, or brain-size correlations with shape differences were found.

  8. 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.

  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. 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

  11. 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.

  12. 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

  13. Intervention-induced enhancement in intrinsic brain activity in healthy older adults

    PubMed Central

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

    2014-01-01

    This study examined the effects of a multimodal intervention on spontaneous brain activity in healthy older adults. Seventeen older adults received a six-week intervention that consisted of cognitive training, Tai Chi exercise, and group counseling, while 17 older adults in a control group attended health knowledge lectures. The intervention group demonstrated enhanced memory and social support compared to the control group. The amplitude of low frequency fluctuations (ALFF) in the middle frontal gyrus, superior frontal gyrus, and anterior cerebellum lobe was enhanced for the intervention group, while the control group showed reduced ALFF in these three regions. Moreover, changes in trail-making performance and well-being could be predicted by the intervention-induced changes in ALFF. Additionally, individual differences in the baseline ALFF were correlated with intervention-related changes in behavioral performance. These findings suggest that a multimodal intervention is effective in improving cognitive functions and well-being and can induce functional changes in the aging brain. The study extended previous training studies by suggesting resting-state ALFF as a marker of intervention-induced plasticity in older adults. PMID:25472002

  14. Functional brain connectivity and cognition: effects of adult age and task demands.

    PubMed

    Chou, Ying-Hui; Chen, Nan-Kuei; Madden, David J

    2013-08-01

    Previous neuroimaging research has documented that patterns of intrinsic (resting state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging data, and RT measures of visual search performance, from 21 younger adults (19-29 years old) and 21 healthy, older adults (60-87 years old). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among 8 pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.

  15. High-Resolution Magnetic Resonance Angiography of the Mouse Brain: Application to Murine Focal Cerebral Ischemia Models

    NASA Astrophysics Data System (ADS)

    Beckmann, Nicolau; Stirnimann, Roger; Bochelen, Damien

    1999-10-01

    Three-dimensional time-of-flight high-resolution magnetic resonance angiography was applied to visualize the cerebral vasculature of the mouse brain. In normal mice, angiograms of good quality, showing the essential details of the arterial cerebrovascular anatomy, could be obtained in only 2.5 min without the use of contrast agents. Signals from slowly flowing blood, e.g., in veins, could also be detected after administration of a blood pool contrast agent. The technique was applied to mouse models of permanent and transient brain ischemia, involving the occlusion of the middle cerebral artery. High-resolution magnetic resonance angiography proved to be a very useful tool for verifying the success of the occlusion in these models.

  16. Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

    PubMed

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

  17. Brain-derived neurotrophic and immunologic factors: beneficial effects of riboflavin on motor disability in murine model of multiple sclerosis

    PubMed Central

    Naghashpour, Mahshid; Amani, Reza; Sarkaki, Alireza; Ghadiri, Ata; Samarbafzadeh, Alireza; Jafarirad, Sima; Malehi, Amal Saki

    2016-01-01

    Objective(s): In the present study, C57BL/6 female mice (n=56) were used to explore the neuroprotective effects of riboflavin in motor disability of experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis. Materials and Methods: The animals were assigned into 7 groups: sham-operated 1 (SO1), healthy mice receiving PBS (phosphate buffer saline); sham-operated 2 (SO2), healthy mice receiving PBS and riboflavin; sham treatment 1 (ST1), EAE mice receiving water; sham treatment 2 (ST2), EAE mice receiving sodium acetate buffer; treatment 1 (T1), EAE mice receiving interferon beta-1a (INFβ-1a); treatment 2 (T2), EAE mice receiving riboflavin; treatment 3 (T3), EAE mice receiving INFβ-1a and riboflavin. After EAE induction, scoring was performed based on clinical signs. Upon detecting score 0.5, riboflavin at 10 mg/kg of body weight and/or INFβ-1a at 150 IU/g of body weight administration was started for two weeks. The brain and spinal cord levels of brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-17A (IL-17A) were studied using real-time PCR and ELISA methods. Results: BDNF expression and protein levels were increased in the brain and spinal cord of the T3 group compared with the other groups (P<0.01). IL-6 and IL-17A expressions were increased in the brains of the T3 and T1 groups, respectively, compared to the other groups (P<0.01). The daily clinical score was reduced significantly by riboflavin in both effector and chronic phases of the disease compared with that of the controls (P<0.05). Conclusion: Our findings showed that riboflavin is capable of suppressing the neurological disability mediated by BDNF and IL-6. PMID:27279989

  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. Persistent production of neurons from adult brain stem cells during recovery after stroke.

    PubMed

    Thored, Pär; Arvidsson, Andreas; Cacci, Emanuele; Ahlenius, Henrik; Kallur, Therése; Darsalia, Vladimer; Ekdahl, Christine T; Kokaia, Zaal; Lindvall, Olle

    2006-03-01

    Neural stem cells in the subventricular zone of adult rodents produce new striatal neurons that may replace those that have died after stroke; however, the neurogenic response has been considered acute and transient, yielding only small numbers of neurons. In contrast, we show herein that striatal neuroblasts are generated without decline at least for 4 months after stroke in adult rats. Neuroblasts formed early or late after stroke either differentiate into mature neurons, which survive for several months, or die through caspase-mediated apoptosis. The directed migration of the new neurons toward the ischemic damage is regulated by stromal cell-derived factor-1alpha and its receptor CXCR4. These results show that endogenous neural stem cells continuously supply the injured adult brain with new neurons, which suggests novel self-repair strategies to improve recovery after stroke. PMID:16210404

  20. A Translational Murine Model of Sub-Lethal Intoxication with Shiga Toxin 2 Reveals Novel Ultrastructural Findings in the Brain Striatum

    PubMed Central

    Tironi-Farinati, Carla; Geoghegan, Patricia A.; Cangelosi, Adriana; Pinto, Alipio; Loidl, C. Fabian; Goldstein, Jorge

    2013-01-01

    Infection by Shiga toxin-producing Escherichia coli causes hemorrhagic colitis, hemolytic uremic syndrome (HUS), acute renal failure, and also central nervous system complications in around 30% of the children affected. Besides, neurological deficits are one of the most unrepairable and untreatable outcomes of HUS. Study of the striatum is relevant because basal ganglia are one of the brain areas most commonly affected in patients that have suffered from HUS and since the deleterious effects of a sub-lethal dose of Shiga toxin have never been studied in the striatum, the purpose of this study was to attempt to simulate an infection by Shiga toxin-producing E. coli in a murine model. To this end, intravenous administration of a sub-lethal dose of Shiga toxin 2 (0.5 ηg per mouse) was used and the correlation between neurological manifestations and ultrastructural changes in striatal brain cells was studied in detail. Neurological manifestations included significant motor behavior abnormalities in spontaneous motor activity, gait, pelvic elevation and hind limb activity eight days after administration of the toxin. Transmission electron microscopy revealed that the toxin caused early perivascular edema two days after administration, as well as significant damage in astrocytes four days after administration and significant damage in neurons and oligodendrocytes eight days after administration. Interrupted synapses and mast cell extravasation were also found eight days after administration of the toxin. We thus conclude that the chronological order of events observed in the striatum could explain the neurological disorders found eight days after administration of the toxin. PMID:23383285

  1. CDK5RAP2 expression during murine and human brain development correlates with pathology in primary autosomal recessive microcephaly.

    PubMed

    Issa, Lina; Kraemer, Nadine; Rickert, Christian H; Sifringer, Marco; Ninnemann, Olaf; Stoltenburg-Didinger, Gisela; Kaindl, Angela M

    2013-09-01

    Homozygous mutations in the cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 cause primary autosomal recessive microcephaly (MCPH). MCPH is characterized by a pronounced reduction of brain volume, particularly of the cerebral cortex, and mental retardation. Though it is a rare developmental disorder, MCPH has moved into the spotlight of neuroscience because of its proposed central role in stem-cell biology and brain development. Investigation of the neural basis of genetically defined MCPH has been limited to animal studies and neuroimaging of affected patients as no neuropathological studies have been published. In the present study, we depict the spatiotemporal expression of CDK5RAP2 in the developing brain of mouse and human. We found intriguing concordance between regions of high CDK5RAP2 expression in the mouse and sites of pathology suggested by neuroimaging studies in humans and mouse. Our findings in human tissue confirm those in mouse tissues, underlining the function of CDK5RAP2 in cell proliferation and arguing for a conserved role of this protein in the development of the mammalian cerebral cortex. PMID:22806269

  2. Effects of fractionated radiation on the brain vasculature in a murine model: Blood-brain barrier permeability, astrocyte proliferation, and ultrastructural changes

    SciTech Connect

    Yuan Hong; Gaber, M. Waleed . E-mail: wgaber@utmem.edu; Boyd, Kelli; Wilson, Christy M.; Kiani, Mohammad F.; Merchant, Thomas E.

    2006-11-01

    Purpose: Radiation therapy of CNS tumors damages the blood-brain barrier (BBB) and normal brain tissue. Our aims were to characterize the short- and long-term effects of fractionated radiotherapy (FRT) on cerebral microvasculature in mice and to investigate the mechanism of change in BBB permeability in mice. Methods and Materials: Intravital microscopy and a cranial window technique were used to measure BBB permeability to fluorescein isothiocyanate (FITC)-dextran and leukocyte endothelial interactions before and after cranial irradiation. Daily doses of 2 Gy were delivered 5 days/week (total, 40 Gy). We immunostained the molecules to detect the expression of glial fibrillary acidic protein and to demonstrate astrocyte activity in brain parenchyma. To relate the permeability changes to endothelial ultrastructural changes, we used electron microscopy. Results: Blood-brain barrier permeability did not increase significantly until 90 days after FRT, at which point it increased continuously until 180 days post-FRT. The number of adherent leukocytes did not increase during the study. The number of astrocytes in the cerebral cortex increased significantly; vesicular activity in endothelial cells increased beginning 90 days after irradiation, and most tight junctions stayed intact, although some were shorter and less dense at 120 and 180 days. Conclusions: The cellular and microvasculature response of the brain to FRT is mediated through astrogliosis and ultrastructural changes, accompanied by an increase in BBB permeability. The response to FRT is delayed as compared with single-dose irradiation treatment, and does not involve leukocyte adhesion. However, FRT induces an increase in the BBB permeability, as in the case of single-dose irradiation.

  3. Resting state fMRI entropy probes complexity of brain activity in adults with ADHD.

    PubMed

    Sokunbi, Moses O; Fung, Wilson; Sawlani, Vijay; Choppin, Sabine; Linden, David E J; Thome, Johannes

    2013-12-30

    In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of P<0.05 (P=0.001, initial threshold). Our findings support the hypothesis of abnormal frontal-striatal-cerebellar circuits in ADHD and the suggestion that sample entropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Brain activation during visual working memory correlates with behavioral mobility performance in older adults.

    PubMed

    Kawagoe, Toshikazu; Suzuki, Maki; Nishiguchi, Shu; Abe, Nobuhito; Otsuka, Yuki; Nakai, Ryusuke; Yamada, Minoru; Yoshikawa, Sakiko; Sekiyama, Kaoru

    2015-01-01

    Functional mobility and cognitive function often decline with age. We previously found that functional mobility as measured by the Timed Up and Go Test (TUG) was associated with cognitive performance for visually-encoded (i.e., for location and face) working memory (WM) in older adults. This suggests a common neural basis between TUG and visual WM. To elucidate this relationship further, the present study aimed to examine the neural basis for the WM-mobility association. In accordance with the well-known neural compensation model in aging, we hypothesized that "attentional" brain activation for easy WM would increase in participants with lower mobility. The data from 32 healthy older adults were analyzed, including brain activation during easy WM tasks via functional Magnetic Resonance Imaging (fMRI) and mobility performance via both TUG and a simple walking test. WM performance was significantly correlated with TUG but not with simple walking. Some prefrontal brain activations during WM were negatively correlated with TUG performance, while positive correlations were found in subcortical structures including the thalamus, putamen and cerebellum. Moreover, activation of the subcortical regions was significantly correlated with WM performance, with less activation for lower WM performers. These results indicate that older adults with lower mobility used more cortical (frontal) and fewer subcortical resources for easy WM tasks. To date, the frontal compensation has been proposed separately in the motor and cognitive domains, which have been assumed to compensate for dysfunction of the other brain areas; however, such dysfunction was less clear in previous studies. The present study observed such dysfunction as degraded activation associated with lower performance, which was found in the subcortical regions. We conclude that a common dysfunction-compensation activation pattern is likely the neural basis for the association between visual WM and functional mobility.

  9. 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

  10. 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

  11. The effect of diesel exhaust exposure on blood-brain barrier integrity and function in a murine model.

    PubMed

    Heidari Nejad, Sayeh; Takechi, Ryusuke; Mullins, Benjamin J; Giles, Corey; Larcombe, Alexander N; Bertolatti, Dean; Rumchev, Krassi; Dhaliwal, Satvinder; Mamo, John

    2015-01-01

    Epidemiological studies indicate that exposure to diesel exhaust (DE) is associated with vascular-based disorders. To investigate the effect of DE on blood-brain barrier (BBB) function and integrity, 8-week-old BALB/c mice were randomized to DE in a cyclical treatment regimen over a 2-week period. Functional integrity of BBB was determined by considering brain parenchymal abundance of IgG within the hippocampal formation and cortex at 6 h and 24 h intervals following final exposure treatment. Neurovascular inflammation was expressed as the abundance of glial fibrillar acidic protein. Two doses of DE were studied and compared to air-only treated mice. Mice exposed to DE had substantially greater abundance of parenchymal IgG compared to control mice not exposed to DE. Increased parenchymal glial fibrillar acidic protein at 24 h post-DE exposure suggested heightened neurovascular inflammation. Our findings are proof-of-concept that inhalation of DE can compromise BBB function and support the broader contention that DE exposure may contribute to neurovascular disease risk.

  12. Epigenetic Gene Regulation in the Adult Mammalian Brain: Multiple roles in Memory Formation

    PubMed Central

    Lubin, Farah D.

    2011-01-01

    Brain-derived neurotrophic factor (bdnf) is one of numerous gene products necessary for long-term memory formation and dysregulation of bdnf has been implicated in the pathogenesis of cognitive and mental disorders. Recent work indicates that epigenetic-regulatory mechanisms including the markings of histone proteins and associated DNA remain labile throughout the lifespan and represent an attractive molecular process contributing to gene regulation in the brain. In this review, important information will be discussed on epigenetics as a set of newly identified dynamic transcriptional mechanisms serving to regulate gene expression changes in the adult brain with particular emphasis on bdnf transcriptional readout in learning and memory formation. This review will also highlight evidence for the role of epigenetics in aberrant bdnf gene regulation in the pathogenesis of cognitive dysfunction associated with seizure disorders, Rett syndrome, Schizophrenia, and Alzheimer’s disease. Such research offers novel concepts for understanding epigenetic transcriptional mechanisms subserving adult cognition and mental health, and furthermore promises novel avenues for therapeutic approach in the clinic. PMID:21419233

  13. 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

  14. Antenatal Maternal Stress Alters Functional Brain Responses In Adult Offspring During Conditioned Fear

    PubMed Central

    Sadler, Theodore R.; Nguyen, Peter T.; Yang, Jun; Givrad, Tina K.; Mayer, Emeran A.; Maarek, Jean-Michel I.; Hinton, David R.; Holschneider, Daniel P.

    2011-01-01

    Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the 14C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility (‘freezing’). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, nucleus acumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation. PMID:21300034

  15. 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.

  16. The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI

    PubMed Central

    Katz, Mindy J.; Lipton, Michael L.; Lipton, Richard B.; Verghese, Joe

    2015-01-01

    Introduction While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia. Methods Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated. Results Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures. Conclusions Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population. PMID:25921321

  17. Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model

    PubMed Central

    Shultz, Michael D.; Wilson, John D.; Fuller, Christine E.; Zhang, Jianyuan; Dorn, Harry C.

    2011-01-01

    Purpose: To demonstrate in an orthotopic xenograft brain tumor model that a functionalized metallofullerene (f-Gd3N@C80) can enable longitudinal tumor imaging and, when radiolabeled with lutetium 177 (177Lu) and tetraazacyclododecane tetraacetic acid (DOTA) (177Lu-DOTA-f-Gd3N@C80), provide an anchor to deliver effective brachytherapy. Materials and Methods: All experiments involving the use of mice were carried out in accordance with protocols approved by the institutional animal care and use committee. Human glioblastoma U87MG cells were implanted by using stereotactic procedures into the brains of 37 female athymic nude-Foxn1nu mice and allowed to develop into a tumor for 8 days. T1- and T2-weighted magnetic resonance (MR) imaging was performed in five mice. Biodistribution studies were performed in 12 mice at four time points over 7 days to evaluate gadolinium content. Survival studies involved 20 mice that received infusion of a nanoplatform by means of convection-enhanced delivery (CED) 8 days after tumor implantation. Mice in survival studies were divided into two groups: one comprised untreated mice that received f-Gd3N@C80 alone and the other comprised mice treated with brachytherapy that received 1.11 MBq of 177Lu-DOTA-f-Gd3N@C80. Survival data were evaluated by using Kaplan-Meier statistical methods. Results: MR imaging showed extended tumor retention (25.6% ± 1.2 of the infused dose at 52 days, confirmed with biodistribution studies) of the f-Gd3N@C80 nanoplatform, which enabled longitudinal imaging. Successful coupling of 177Lu to the f-Gd3N@C80 surface was achieved by using a bifunctional macrocyclic chelator. The extended tumor retention allowed for effective brachytherapy, as indicated by extended survival time (>2.5 times that of the untreated group) and histologic signs of radiation-induced tumor damage. Conclusion: The authors have developed a multimodal nanoplatform and have demonstrated longitudinal tumor imaging, prolonged intratumoral probe

  18. 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.

  19. Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location, and cotransmitters.

    PubMed

    Sundvik, Maria; Panula, Pertti

    2012-12-01

    Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire histaminergic neuron population in adult male and female zebrafish brain and quantified the histaminergic neuron numbers. There were 40-45 histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep-wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors.

  20. 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

  1. Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome.

    PubMed

    Hartley, Sigan L; Handen, Benjamin L; Devenny, Darlynne A; Hardison, Regina; Mihaila, Iulia; Price, Julie C; Cohen, Annie D; Klunk, William E; Mailick, Marsha R; Johnson, Sterling C; Christian, Bradley T

    2014-09-01

    Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P < 0.0001) between age and neocortical Pittsburgh compound B retention. This robust association makes it difficult to discriminate normative age-related decline in cognitive functioning from any potential effects of amyloid-β deposition. When controlling for chronological age in addition to mental age, there were no significant differences between the adults with Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-β deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-β deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-β deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.

  2. Augmented efficacy with the combination of blockade of the Notch-1 pathway, bortezomib and romidepsin in a murine MT-1 adult T-cell leukemia model.

    PubMed

    Yu, P; Petrus, M N; Ju, W; Zhang, M; Conlon, K C; Nakagawa, M; Maeda, M; Bamford, R N; Waldmann, T A

    2015-03-01

    Adult T-cell leukemia (ATL) is an aggressive malignancy caused by human T-cell lymphotropic virus-1. There is no accepted curative therapy for ATL. We have reported that certain ATL patients have increased Notch-1 signaling along with constitutive activation of the nuclear factor-κB pathway. Physical and functional interaction between these two pathways provides the rationale to combine the γ-secretase inhibitor compound E with the proteasome inhibitor bortezomib. Moreover, romidepsin, a histone deacetylase inhibitor, has demonstrated major antitumor action in leukemia/lymphoma. In this study, we investigated the therapeutic efficacy of the single agents and the combination of these agents in a murine model of human ATL, the MT-1 model. Single and double agents inhibited tumor growth as monitored by tumor size (P<0.05), and prolonged survival of leukemia-bearing mice (P<0.05) compared with the control group. The combination of three agents significantly enhanced the antitumor efficacy as assessed by tumor size, tumor markers in the serum (human soluble interleukin-2 receptor-α and β2-microglobulin) and survival of the MT-1 tumor-bearing mice, compared with all other treatment groups (P<0.05). Improved therapeutic efficacy obtained by combining compound E, bortezomib and romidepsin supports a clinical trial of this combination in the treatment of ATL.

  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.

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

    PubMed

    Zhang, Kuan; Zhou, Yanzhao; Zhao, Tong; 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.

  5. 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

  6. Beyond Utterances: Distributed Cognition as a Framework for Studying Discourse in Adults with Acquired Brain Injury

    PubMed Central

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

    2014-01-01

    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

  7. 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

  8. Cellular distribution and localisation of iron in adult rat brain ( substantia nigra)

    NASA Astrophysics Data System (ADS)

    Meinecke, Ch.; Morawski, M.; Reinert, T.; Arendt, T.; Butz, T.

    2006-08-01

    Iron appears to be one of the main factors in the metal induced neurodegeneration. Quantitative information on cellular, sub-cellular and cell specific distributions of iron is therefore important to assess. The investigations reported here were carried out on a brain from an adult rat. Therefore, 6 μm thick embedded, unstained brain sections containing the midbrain (substantia nigra, SN) were analysed. Particle induced X-ray emission (PIXE) using a focussed proton beam (beam - diameter app. 1 μm) was performed to determine the quantitative iron content on a cellular and sub-cellular level. The integral analysis shows that the iron content in the SN pars reticulata is twice as high than in the SN pars compacta. The analysis of the iron content on the cellular level revealed no remarkable differences between glia cells and neurons. This is in contrast to other studies using staining techniques.

  9. Consensus brain-derived protein, extraction protocol for the study of human and murine brain proteome using both 2D-DIGE and mini 2DE immunoblotting.

    PubMed

    Fernandez-Gomez, Francisco-Jose; Jumeau, Fanny; Derisbourg, Maxime; Burnouf, Sylvie; Tran, Hélène; Eddarkaoui, Sabiha; Obriot, Hélène; Dutoit-Lefevre, Virginie; Deramecourt, Vincent; Mitchell, Valérie; Lefranc, Didier; Hamdane, Malika; Blum, David; Buée, Luc; Buée-Scherrer, Valérie; Sergeant, Nicolas

    2014-01-01

    Two-dimensional gel electrophoresis (2DE) is a powerful tool to uncover proteome modifications potentially related to different physiological or pathological conditions. Basically, this technique is based on the separation of proteins according to their isoelectric point in a first step, and secondly according to their molecular weights by SDS polyacrylamide gel electrophoresis (SDS-PAGE). In this report an optimized sample preparation protocol for little amount of human post-mortem and mouse brain tissue is described. This method enables to perform both two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mini 2DE immunoblotting. The combination of these approaches allows one to not only find new proteins and/or protein modifications in their expression thanks to its compatibility with mass spectrometry detection, but also a new insight into markers validation. Thus, mini-2DE coupled to western blotting permits to identify and validate post-translational modifications, proteins catabolism and provides a qualitative comparison among different conditions and/or treatments. Herein, we provide a method to study components of protein aggregates found in AD and Lewy body dementia such as the amyloid-beta peptide and the alpha-synuclein. Our method can thus be adapted for the analysis of the proteome and insoluble proteins extract from human brain tissue and mice models too. In parallel, it may provide useful information for the study of molecular and cellular pathways involved in neurodegenerative diseases as well as potential novel biomarkers and therapeutic targets. PMID:24747743

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

    PubMed

    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 (two of these also had pituitary dysfunction). 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.

  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. 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

  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. Hippotherapy in Adult Patients with Chronic Brain Disorders: A Pilot Study

    PubMed Central

    Sunwoo, Hyuk; Kwon, Jeong-Yi; Kim, Tae-Won; Lee, Ji-Young; Kim, Yun-Hee

    2012-01-01

    Objective To investigate the effects of hippotherapy for adult patients with brain disorders. Method Eight chronic brain disorder patients (7 males, mean age 42.4±16.6 years) were recruited. The mean duration from injury was 7.9±7.7 years. The diagnoses were stroke (n=5), traumatic brain disorder (n=2), and cerebral palsy (n=1). Hippotherapy sessions were conducted twice a week for eight consecutive weeks in an indoor riding arena. Each hippotherapy session lasted 30 minutes. All participants were evaluated by the Berg balance scale, Tinetti Performance-Oriented Mobility Assessment, 10 Meter Walking Test, Functional Ambulatory Category, Korean Beck Depression Inventory, and Hamilton Depression Rating Scale. We performed baseline assessments twice just before starting hippotherapy. We also assessed the participants immediately after hippotherapy and at eight weeks after hippotherapy. Results All participants showed no difference in balance, gait function, and emotion between the two baseline assessments before hippotherapy. During the eight-week hippotherapy program, all participants showed neither adverse effects nor any accidents; all had good compliance. After hippotherapy, there were significant improvements in balance and gait speed in comparison with the baseline assessment (p<0.05), and these effects were sustained for two months after hippotherapy. However, there was no significant difference in emotion after hippotherapy. Conclusion We could observe hippotherapy to be a safe and effective alternative therapy for adult patients with brain disorders in improving balance and gait function. Further future studies are warranted to delineate the benefits of hippotherapy on chronic stroke patients. PMID:23342306

  15. Carbon Monoxide Modulates Cytochrome Oxidase Activity and Oxidative Stress in the Developing Murine Brain During Isoflurane Exposure

    PubMed Central

    Cheng, Ying; Mitchell-Flack, Marisa J.; Wang, Aili; Levy, Richard J.

    2015-01-01

    Commonly used anesthetics induce widespread neuronal degeneration in the developing mammalian brain via the oxidative stress-associated mitochondrial apoptosis pathway. Dysregulation of cytochrome oxidase (CcOX), the terminal oxidase of the electron transport chain, can result in reactive oxygen species (ROS) formation and isoflurane has previously been shown to activate this enzyme. Carbon monoxide (CO), as a modulator of CcOX, is of interest because infants and children are routinely exposed to CO during low-flow anesthesia. We have recently demonstrated that low concentrations of CO limit and prevent isoflurane-induced neurotoxicity in the forebrain of newborn mice in a dose-dependent manner. However, the effect of CO on CcOX in the context of anesthetic-induced oxidative stress is unknown. Seven day old male CD-1 mice underwent 1-hour exposure to 0 ppm (air), 5 ppm, or 100 ppm CO in air with or without isoflurane. Exposure to isoflurane or CO independently increased CcOX kinetic activity and increased ROS within forebrain mitochondria. However, combined exposure to CO with isoflurane paradoxically limited CcOX activation and oxidative stress. There were no changes seen in steady-state levels of CcOX I protein indicating post-translational modification of CcOX as an etiology for changes in enzyme activity. CO exposure led to differential effects on CcOX subunit I tyrosine phosphorylation depending on concentration, while combined exposure to isoflurane with CO markedly increased enzyme phosphorylation state. Phosphorylation of tyrosine 304 of CcOX subunit I has been shown to result in strong enzyme inhibition, and the relative reduction in CcOX kinetics following combined exposure to CO with isoflurane may have been due, in part, to such phosphorylation. Taken together, the data suggest that CO modulates CcOX in the developing brain during isoflurane exposure, thereby limiting oxidative stress. These CO-mediated effects could have implications for the

  16. EBIC-guidelines for management of severe head injury in adults. European Brain Injury Consortium.

    PubMed

    Maas, A I; Dearden, M; Teasdale, G M; Braakman, R; Cohadon, F; Iannotti, F; Karimi, A; Lapierre, F; Murray, G; Ohman, J; Persson, L; Servadei, F; Stocchetti, N; Unterberg, A

    1997-01-01

    Guidelines for the management of severe head injury in adults as evolved by the European Brain Injury Consortium are presented and discussed. The importance of preventing and treating secondary insults is emphasized and the principles on which treatment is based are reviewed. Guidelines presented are of a pragmatic nature, based on consensus and expert opinion, covering the treatment from accident site to intensive care unit. Specific aspects pertaining to the conduct of clinical trials in head injury are highlighted. The adopted approach is further discussed in relation to other approaches to the development of guidelines, such as evidence based analysis.

  17. 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

  18. Memory reorganization in adult brain: observations in three patients with temporal lobe epilepsy.

    PubMed

    Gleissner, Ulrike; Helmstaedter, Christoph; Elger, Christian Erich

    2002-02-01

    We present three patients with left-sided temporal lobe epilepsy who exhibited preoperatively a neuropsychological pattern characteristic for interhemispheric language transfer (marked nonverbal memory deficits, relatively preserved verbal memory and language performance). The Wada test indicated atypical language dominance in two patients, but one patient was clearly left hemispheric language dominant. All patients showed a marked recovery of nonverbal memory after left-sided surgery. Results are discussed with respect to memory transfer and plasticity for memory functions in the adult brain. PMID:11904242

  19. Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain

    PubMed Central

    van de Lagemaat, Louie N.; Nijhof, Bonnie; Bosch, Daniëlle G. M.; Kohansal-Nodehi, Mahdokht; Keerthikumar, Shivakumar; Heimel, J. Alexander

    2014-01-01

    Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause. PMID:25538548

  20. 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.

  1. Abstracting meaning from complex information (gist reasoning) in adult traumatic brain injury.

    PubMed

    Vas, Asha Kuppachi; Spence, Jeffrey; Chapman, Sandra Bond

    2015-01-01

    Gist reasoning (abstracting meaning from complex information) was compared between adults with moderate-to-severe traumatic brain injury (TBI, n = 30) at least one year post injury and healthy adults (n = 40). The study also examined the contribution of executive functions (working memory, inhibition, and switching) and memory (immediate recall and memory for facts) to gist reasoning. The correspondence between gist reasoning and daily function was also examined in the TBI group. Results indicated that the TBI group performed significantly lower than the control group on gist reasoning, even after adjusting for executive functions and memory. Executive function composite was positively associated with gist reasoning (p < .001). Additionally, performance on gist reasoning significantly predicted daily function in the TBI group beyond the predictive ability of executive function alone (p = .011). Synthesizing and abstracting meaning(s) from information (i.e., gist reasoning) could provide an informative index into higher order cognition and daily functionality. PMID:25633568

  2. Reactive changes of retinal microglia during fatal murine cerebral malaria: effects of dexamethasone and experimental permeabilization of the blood-brain barrier.

    PubMed

    Medana, I M; Chan-Ling, T; Hunt, N H

    2000-03-01

    Microglial activation and redistribution toward blood vessels are some of the earliest observable events occurring within the central nervous system (CNS) during fatal murine cerebral malaria (FMCM). To investigate stimuli that might modulate microglial reactivity during FMCM we have performed two experimental manipulations and observed microglial responses in retinal whole mounts. First, to determine whether increased blood-brain barrier (BBB) permeability in the absence of the malaria parasite initiates the microglial changes, BBB function was compromised experimentally by intracarotid injection of arabinose and retinae were examined 12, 24, or 36 hours later. Second, to determine whether the immune response against the malaria parasite modulates microglial reactivity, infected mice were treated with dexamethasone before day 4 postinoculation. This treatment regime ameliorates cerebral complications without affecting parasite growth. We observed that increased BBB permeability was sufficient to elicit thickening of microglial processes and redistribution of microglia toward the vasculature, characteristic of the early stages of FMCM. However, despite the presence of plasma constituents in the CNS for up to 36 hours, microglia with amoeboid and vacuolated morphology were not observed. Dexamethasone treatment inhibited the up-regulation of alpha-D-galactose expression and reactive morphological changes in microglia during FMCM. These results suggest that disruption of the CNS milieu by entry of plasma constituents, or circulating malaria parasites in the absence of an immune response, by themselves are insufficient to induce the reactive microglial changes that are characteristic of FMCM. In addition, dexamethasone-sensitive event(s), presumably associated with immune system activation, occurring within the first few days of malaria infection are essential for the development of reactive microglia and subsequent fatal neurological complications.

  3. Radio frequency energy harvesting from a feeding source in a passive deep brain stimulation device for murine preclinical research.

    PubMed

    Hosain, Md Kamal; Kouzani, Abbas Z; Tye, Susannah J; Samad, Mst Fateha; Kale, Rajas P; Bennet, Kevin E; Manciu, Felicia S; Berk, Michael

    2015-10-01

    This paper presents the development of an energy harvesting circuit for use with a head-mountable deep brain stimulation (DBS) device. It consists of a circular planar inverted-F antenna (PIFA) and a Schottky diode-based Cockcroft-Walton 4-voltage rectifier. The PIFA has the volume of π × 10(2) × 1.5 mm(3), resonance frequency of 915 MHz, and bandwidth of 16 MHz (909-925 MHz) at a return loss of -10 dB. The rectifier offers maximum efficiency of 78% for the input power of -5 dBm at a 5 kΩ load resistance. The developed rectenna operates efficiently at 915 MHz for the input power within -15 dBm to +5 dBm. For operating a DBS device, the DC voltage of 2 V is recorded from the rectenna terminal at a distance of 55 cm away from a 26.77 dBm transmitter in free space. An in-vitro test of the DBS device is presented. PMID:26318799

  4. CNF1 Increases Brain Energy Level, Counteracts Neuroinflammatory Markers and Rescues Cognitive Deficits in a Murine Model of Alzheimer's Disease

    PubMed Central

    Travaglione, Sara; Fabbri, Alessia; Guidotti, Marco; Ferri, Alberto; Campana, Gabriele; Fiorentini, Carla

    2013-01-01

    Overexpression of pro-inflammatory cytokines and cellular energy failure are associated with neuroinflammatory disorders, such as Alzheimer's disease. Transgenic mice homozygous for human ApoE4 gene, a well known AD and atherosclerosis animal model, show decreased levels of ATP, increased inflammatory cytokines level and accumulation of beta amyloid in the brain. All these findings are considered responsible for triggering cognitive decline. We have demonstrated that a single administration of the bacterial E. coli protein toxin CNF1 to aged apoE4 mice, beside inducing a strong amelioration of both spatial and emotional memory deficits, favored the cell energy restore through an increment of ATP content. This was accompanied by a modulation of cerebral Rho and Rac1 activity. Furthermore, CNF1 decreased the levels of beta amyloid accumulation and interleukin-1β expression in the hippocampus. Altogether, these data suggest that the pharmacological modulation of Rho GTPases by CNF1 can improve memory performances in an animal model of Alzheimer's disease via a control of neuroinflammation and a rescue of systemic energy homeostasis. PMID:23738020

  5. Isolation and characterization of primary microglia from post-natal murine brain tissues: a comparison of two methods.

    PubMed

    Jose, Shinsmon; Tan, Shi Wei; Tong, Chih Kong; Vidyadaran, Sharmili

    2015-12-01

    Microglia are resident macrophages of the central nervous system (CNS). Apart from playing vital roles as sentinel cells, they are crucial in physiological processes such as synaptic pruning during brain development. CNS disorders require an understanding of the contribution of each cellular compartment to the pathogenesis. Elucidating the role of microglia in disease development and progression in the intricate CNS environment is technically challenging and requires the establishment of reliable, reproducible techniques to isolate and culture microglia. A number of different protocols have been developed for isolation of neonatal microglia and here we compare two widely used methods, namely, mild trypsinization and EasySep® magnetic separation. EasySep® magnetic separation provided higher microglia yield, and flow cytometric evaluation of CD11b and F4/80 markers revealed that EasySep® separation method also produced significantly higher purity compared to mild trypsinization. Microglia isolated using EasySep® separation method were functional, as demonstrated by the generation of nitric oxide, IL-6, TNF-α, and MCP-1 in response to lipopolysaccharide stimulation. In summary, this study has revealed that magnetic separation is superior to mild trypsinization in terms of yield and purity of microglia.

  6. 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.

  7. 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

  8. 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

  9. New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains

    PubMed Central

    Miyata, Seiji

    2015-01-01

    The blood–brain barrier (BBB) generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs), which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP), have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs) sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF) signaling may be involved in angiogenesis and neurogliogenesis, both

  10. 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 ...

  11. 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.

  12. Expression pattern of STOP lacZ reporter gene in adult and developing mouse brain.

    PubMed

    Couégnas, Alice; Schweitzer, Annie; Andrieux, Annie; Ghandour, M Said; Boehm, Nelly

    2007-05-15

    Stable tubulin-only polypeptide (STOP) proteins are microtubule-associated proteins responsible for microtubule stabilization in neurons. STOP null mice show apparently normal cerebral anatomy but display synaptic defects associated with neuroleptic-sensitive behavioral disorders. STOP null mice have therefore been proposed as an animal model for the study of schizophrenia. In the present study, the expression pattern of STOP gene in developing and adult brain has been examined by using lacZ gene inserted in the STOP locus, as a reporter gene. beta-Galactosidase (beta-gal) immunostaining was confined to neuronal cells and projections. Strong labeling was observed in the whole olfactory system, cortical layer VII, hippocampus, hypothalamus, cerebellum, habenula, fasciculus retroflexus, and interpeduncular nucleus in adults. Additionally, ventral thalamic nucleus, clusters of positive cells in striatum, and Cajal-Retzius cells of cortical layer I were labeled in young mice. The strong expression of STOP lacZ reporter gene observed in brain is confined to areas that may be involved in the schizophrenia-related symptoms observed in STOP-deficient mice.

  13. 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

  14. Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

    PubMed

    Chabok, Shahrokh Yousefzadeh; Kapourchali, Sara Ramezani; Leili, Ehsan Kazemnezhad; Saberi, Alia; Mohtasham-Amiri, Zahra

    2012-06-01

    Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.

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

    PubMed

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

    2015-10-14

    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.

  16. ERK phosphorylation in intact, adult brain by alpha(2)-adrenergic transactivation of EGF receptors.

    PubMed

    Du, Ting; Li, Baoman; Liu, Shufang; Zang, Peizhuo; Prevot, Vincent; Hertz, Leif; Peng, Liang

    2009-12-01

    Our previous work demonstrated dexmedetomidine-activated phosphorylation of extracellular regulated kinases 1 and 2 (ERK(1/2)) in primary cultures of mouse astrocytes and showed that it is evoked by alpha(2)-adrenoceptor-mediated transactivation of epidermal growth factor (EGF) receptors, a known response to activation of G(i/o)- or G(q)-coupled receptors [Li, B., Du, T., Li, H., Gu, L., Zhang, H., Huang, J., Hertz, L., Peng, L., 2008a. Signaling pathways for transactivation by dexmedetomidine of epidermal growth factor receptors in astrocytes and its paracrine effect on neurons. Br. J. Pharmacol. 154, 191-203]. Like most studies of transactivation, that study used cultured cells, raising the question whether a similar effect can be demonstrated in intact brain tissue and the brain in vivo. In the present study we have shown that (i) dexmedetomidine-mediated ERK(1/2) phosphorylation occurs in mouse brain slices with a similar concentration dependence as in cultured astrocytes (near-maximum effect at 50nM); (ii) intraperitoneal injection of dexmedetomidine (3microg/kg) in adult mice causes rapid phosphorylation of the EGF receptor (at Y845 and Y992) and of ERK(1/2) in the brain; (iii) both EGF receptor and ERK(1/2) phosphorylation are inhibited by intraventricular administration of (a) AG 1478, a specific inhibitor of the receptor-tyrosine kinase of the EGF receptor; (b) GM 6001, an inhibitor of metalloproteinase(s) required for release of EGF receptor agonists from membrane-bound precursors; or (c) heparin, neutralizing heparin-binding EGF (HB-EGF). Thus, in intact brain HB-EGF, known to be expressed in brain, may be the major EGF agonist released in response to stimulation of alpha(2)-adrenoceptors, the released agonist(s) activate(s) EGF receptors, and ERK(1/2) is phosphorylated as a conventional response to EGF receptor activation. Our previous paper (see above) showed that dexmedetomidine evokes no ERK(1/2) phosphorylation in cultured neurons, but neurons

  17. Ankyrin-binding activity of nervous system cell adhesion molecules expressed in adult brain.

    PubMed

    Davis, J Q; Bennett, V

    1993-01-01

    A family of ankyrin-binding glycoproteins have been identified in adult rat brain that include alternatively spliced products of the same pre-mRNA. A composite sequence of ankyrin-binding glycoprotein (ABGP) shares 72% amino acid sequence identity with chicken neurofascin, a membrane-spanning neural cell adhesion molecule in the Ig super-family expressed in embryonic brain. ABGP polypeptides and ankyrin associate as pure proteins in a 1:1 molar stoichiometry at a site located in the predicted cytoplasmic domain. ABGP polypeptides are expressed late in postnatal development to approximately the same levels as ankyrin, and comprise a significant fraction of brain membrane proteins. Immunofluorescence studies have shown that ABGP polypeptides are co-localized with ankyrinB. Major differences in developmental expression have been reported for neurofascin in embryos compared with the late postnatal expression of ABGP, suggesting that ABGP and neurofascin represent products of gene duplication events that have subsequently evolved in parallel with distinct roles. Predicted cytoplasmic domains of rat ABGP and chicken neurofascin are nearly identical to each other and closely related to a group of nervous system cell adhesion molecules with variable extracellular domains, including L1, Nr-CAM and Ng-CAM of vertebrates, and neuroglian of Drosophila. A hypothesis to be evaluated is that ankyrin-binding activity is shared by all of these proteins.

  18. 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

  19. Neurobiological markers of exercise-related brain plasticity in older adults

    PubMed Central

    Voss, Michelle W.; Erickson, Kirk I.; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S.; Alves, Heloisa; Szabo, Amanda; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L.; Olson, Erin A.; Gothe, Neha; Potter, Vicki V.; Martin, Stephen A.; Pence, Brandt D.; Cook, Marc D.; Woods, Jeffrey A.; McAuley, Edward; Kramer, Arthur F.

    2012-01-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age = 66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF. PMID:23123199

  20. 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

  1. Neurobiological markers of exercise-related brain plasticity in older adults.

    PubMed

    Voss, Michelle W; Erickson, Kirk I; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S; Alves, Heloisa; Szabo, Amanda; Phillips, Siobhan M; Wójcicki, Thomas R; Mailey, Emily L; Olson, Erin A; Gothe, Neha; Vieira-Potter, Victoria J; Martin, Stephen A; Pence, Brandt D; Cook, Marc D; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2013-02-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

  2. 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

  3. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    PubMed

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  4. 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.

  5. 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

  6. 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

  7. Magnetic resonance imaging of the brain in adults with severe falciparum malaria

    PubMed Central

    2014-01-01

    Background Magnetic resonance imaging (MRI) allows detailed study of structural and functional changes in the brain in patients with cerebral malaria. Methods In a prospective observational study in adult Bangladeshi patients with severe falciparum malaria, MRI findings in the brain were correlated with clinical and laboratory parameters, retinal photography and optic nerve sheath diameter (ONSD) ultrasound (a marker of intracranial pressure). Results Of 43 enrolled patients, 31 (72%) had coma and 12 (28%) died. MRI abnormalities were present in 79% overall with mostly mild changes in a wide range of anatomical sites. There were no differences in MRI findings between patients with cerebral and non-cerebral or fatal and non-fatal disease. Subtle diffuse cerebral swelling was common (n = 22/43), but mostly without vasogenic oedema or raised intracranial pressure (ONSD). Also seen were focal extracellular oedema (n = 11/43), cytotoxic oedema (n = 8/23) and mildly raised brain lactate on magnetic resonance spectroscopy (n = 5/14). Abnormalities were much less prominent than previously described in Malawian children. Retinal whitening was present in 36/43 (84%) patients and was more common and severe in patients with coma. Conclusion Cerebral swelling is mild and not specific to coma or death in adult severe falciparum malaria. This differs markedly from African children. Retinal whitening, reflecting heterogeneous obstruction of the central nervous system microcirculation by sequestered parasites resulting in small patches of ischemia, is associated with coma and this process is likely important in the pathogenesis. PMID:24884982

  8. 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

  9. 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

  10. 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

  11. Comparison of in vitro mineralization by murine embryonic and adult stem cells cultured in an osteogenic medium.

    PubMed

    Shimko, Daniel A; Burks, Chris A; Dee, Kay C; Nauman, Eric A

    2004-01-01

    Nearly half a million bone-grafting procedures occurred in the United States in the year 2000. Tissue-engineered bone substitutes may mitigate difficulties associated with current grafting options. Embryonic stem cells (ESCs) could be a potential cell source for bone substitutes; however, direct comparisons between ESCs and other cell sources are lacking. Here we provide a direct, long-term, in vitro comparison of mineralization processes in adult, marrow-derived, mesenchymal stem cells (MSCs) and ESCs from the 129/Sv+c/+p mouse strain. MSCs were observed to grow at a slower rate than ESCs. MSCs expressed seven times more alkaline phosphatase (AP) per cell than did ESCs and immediately showed type I collagen and osteocalcin production. ESCs also produced type I collagen and osteocalcin, but production was delayed. Mineral deposition by ESCs was nearly 50 times higher than by MSCs. Spectroscopic analysis showed the calcium-to-phosphorus ratio (Ca:P) of the ESC mineral (1.26:1) to be significantly higher than that of the MSCs (0.29:1), but still 25% lower than hydroxyapatite (1.67:1). Addition of basic fibroblast growth factor significantly inhibited AP expression, mineral deposition, and Ca:P ratios in MSCs and had little effect on ESCs. These functional characteristics may assist with cell selection for purposes of bone tissue engineering.

  12. Enhanced habit-based learning and decreased neurogenesis in the adult hippocampus in a murine model of chronic social stress.

    PubMed

    Ferragud, A; Haro, A; Sylvain, A; Velázquez-Sánchez, C; Hernández-Rabaza, V; Canales, J J

    2010-06-26

    Stress can induce preferential engagement of habit learning mediated by the basal ganglia, relative to learning that involves complex spatial associations contributed by the hippocampal formation. We explored in mice the influence that chronic episodes of social stress exert on the selection of cognitive/spatial vs. habit-based learning strategies. Male mice were exposed to repeated episodes of social confrontation and were categorized as dominant, subordinate or undetermined according to quantitative ethologically relevant parameters of aggression. Mice were then trained in a conditional discrimination task in the T-maze in the presence of allocentric cues until five correct choices were made. The T-maze was then turned 180 degrees and mice were categorized as "cue-learners" or "place-learners" on the basis of their first response in the probe test. Mice showed a graded preference for place vs. cue learning strategies depending on their social categorization (control>undetermined>dominant>subordinate), which ranged from 55% in controls to only 10% in subordinate mice. The response of subordinate mice differed significantly from controls. Hippocampal neurogenesis was studied in the different groups of mice. In keeping with the tendency to engage habit learning, 2,5-bromodeoxyuridine (BrdU) incorporation in the DG was reduced in mice that experienced agonistic encounters, and so was the expression of doublecortin, a marker for immature neurons. These observations suggest that chronic social stress impairs neurogenesis in the adult hippocampus, weakens spatial learning and strengthens habit-like responses.

  13. 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

  14. 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

  15. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    PubMed Central

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078

  16. 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.

  17. 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

  18. 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

  19. Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain.

    PubMed

    Kuan, Chia-Yi; Schloemer, Aryn J; Lu, Aigang; Burns, Kevin A; Weng, Wei-Lan; Williams, Michael T; Strauss, Kenneth I; Vorhees, Charles V; Flavell, Richard A; Davis, Roger J; Sharp, Frank R; Rakic, Pasko

    2004-11-24

    Recent studies suggest that postmitotic neurons can reenter the cell cycle as a prelude to apoptosis after brain injury. However, most dying neurons do not pass the G1/S-phase checkpoint to resume DNA synthesis. The specific factors that trigger abortive DNA synthesis are not characterized. Here we show that the combination of hypoxia and ischemia induces adult rodent neurons to resume DNA synthesis as indicated by incorporation of bromodeoxyuridine (BrdU) and expression of G1/S-phase cell cycle transition markers. After hypoxia-ischemia, the majority of BrdU- and neuronal nuclei (NeuN)-immunoreactive cells are also terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-stained, suggesting that they undergo apoptosis. BrdU+ neurons, labeled shortly after hypoxia-ischemia, persist for >5 d but eventually disappear by 28 d. Before disappearing, these BrdU+/NeuN+/TUNEL+ neurons express the proliferating cell marker Ki67, lose the G1-phase cyclin-dependent kinase (CDK) inhibitors p16INK4 and p27Kip1 and show induction of the late G1/S-phase CDK2 activity and phosphorylation of the retinoblastoma protein. This contrasts to kainic acid excitotoxicity and traumatic brain injury, which produce TUNEL-positive neurons without evidence of DNA synthesis or G1/S-phase cell cycle transition. These findings suggest that hypoxia-ischemia triggers neurons to reenter the cell cycle and resume apoptosis-associated DNA synthesis in brain. Our data also suggest that the demonstration of neurogenesis after brain injury requires not only BrdU uptake and mature neuronal markers but also evidence showing absence of apoptotic markers. Manipulating the aberrant apoptosis-associated DNA synthesis that occurs with hypoxia-ischemia and perhaps neurodegenerative diseases could promote neuronal survival and neurogenesis.

  20. Suicide ideation in pediatric and adult survivors of childhood brain tumors.

    PubMed

    Brinkman, Tara M; Liptak, Cori C; Delaney, Brian L; Chordas, Christine A; Muriel, Anna C; Manley, Peter E

    2013-07-01

    Survivors of pediatric brain tumors are at risk for long-term psychological morbidities. The current study investigated the prevalence and predictors of suicide ideation (SI) in a clinical sample of youth and adult survivors. Retrospective chart reviews were completed for 319 survivors of pediatric brain tumors who were assessed via clinical interview during routine neuro-oncology clinic visits between 2003 and 2007. Survivors were, on average, 18.0 years of age (SD = 4.9) and 10 years from diagnosis (SD = 5.0) at their most recent follow-up. The most common diagnosis was low-grade glioma (n = 162) followed by embryonal tumors (PNET/medulloblastoma; n = 64). Multivariable logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for SI. Nearly 12 % of survivors (11.7 %, n = 37) reported SI. Five survivors (1.5 %) had documented suicide attempts, though none were fatal. In a multivariable model, adjusting for sex and age, history of depression (OR = 20.6, 95 % CI = 4.2-101.1), psychoactive medication treatment (OR = 4.5, 95 % CI = 1.8-11.2), observation or surgery only treatment (OR = 3.7, 95 % CI = 1.5-9.1), and seizures (OR = 3.6, 95 % CI = 1.1-11.1) were significantly associated with SI in survivors. Survivors of pediatric brain tumors appear to be at risk for experiencing SI. Our results underscore the importance of a multidisciplinary approach to providing follow-up care for childhood brain tumor survivors, including routine psychological screenings.

  1. 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

  2. Prolongation of Relaxation Time in Extraocular Muscles With Brain Derived Neurotrophic Factor in Adult Rabbit

    PubMed Central

    Nelson, Krysta R.; Stevens, Shanlee M.; McLoon, Linda K.

    2016-01-01

    Purpose We tested the hypothesis that short-term treatment with brain derived neurotrophic factor (BDNF) would alter the contractile characteristics of rabbit extraocular muscle (EOM). Methods One week after injections of BDNF in adult rabbit superior rectus muscles, twitch properties were determined in treated and control muscles in vitro. Muscles were also examined for changes in mean cross-sectional areas, neuromuscular junction size, and percent of myofibers expressing specific myosin heavy chain isoforms, and sarcoendoplasmic reticulum calcium ATPases (SERCA) 1 and 2. Results Brain derived neurotrophic factor–treated muscles had prolonged relaxation times compared with control muscles. Time to 50% relaxation, time to 100% relaxation, and maximum rate of relaxation were increased by 24%, 27%, and 25%, respectively. No significant differences were seen in time to peak force, twitch force, or maximum rate of contraction. Brain derived neurotrophic factor treatment significantly increased mean cross-sectional areas of slow twitch and tonic myofibers, with increased areas ranging from 54% to 146%. Brain derived neurotrophic factor also resulted in an increased percentage of slow twitch myofibers in the orbital layers, ranging from 54% to 77%, and slow-tonic myofibers, ranging from 44% to 62%. No significant changes were seen SERCA1 or 2 expression or in neuromuscular junction size. Conclusions Short-term treatment with BDNF significantly prolonged the duration and rate of relaxation time and increased expression of both slow-twitch and slow-tonic myosin-expressing myofibers without changes in neuromuscular junctions or SERCA expression. The changes induced by BDNF treatment might have potential therapeutic value in dampening/reducing uncontrolled eye oscillations in nystagmus. PMID:27802489

  3. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase. PMID:16631439

  4. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

  5. 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

  6. Deregulated proliferation and differentiation in brain tumors

    PubMed Central

    Swartling, Fredrik J; Čančer, Matko; Frantz, Aaron; Weishaupt, Holger; Persson, Anders I

    2014-01-01

    Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment-resistance, suppress tumor growth, and prevent recurrence in patients. PMID:25416506

  7. What underlies the diversity of brain tumors?

    PubMed Central

    Swartling, Fredrik J.; Hede, Sanna-Maria; Weiss, William A.

    2012-01-01

    Glioma and medulloblastoma represent the most commonly occurring malignant brain tumors in adults and in children respectively. Recent genomic and transcriptional approaches present a complex group of diseases, and delineate a number of molecular subgroups within tumors that share a common histopathology. Differences in cells of origin, regional niches, developmental timing and genetic events all contribute to this heterogeneity. In an attempt to recapitulate the diversity of brain tumors, an increasing array of genetically engineered mouse models (GEMMs) has been developed. These models often utilize promoters and genetic drivers from normal brain development, and can provide insight into specific cells from which these tumors originate. GEMMs show promise in both developmental biology and developmental therapeutics. This review describes numerous murine brain tumor models in the context of normal brain development, and the potential for these animals to impact brain tumor research. PMID:23085857

  8. ABAEnrichment: an R package to test for gene set expression enrichment in the adult and developing human brain

    PubMed Central

    Prüfer, Kay; Kelso, Janet; Dannemann, Michael

    2016-01-01

    Summary: We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell-types and developmental stages. Availability and Implementation: ABAEnrichment was implemented as an R package and is available under GPL (≥ 2) from the Bioconductor website (http://bioconductor.org/packages/3.3/bioc/html/ABAEnrichment.html). Contacts: steffi_grote@eva.mpg.de, kelso@eva.mpg.de or michael_dannemann@eva.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354695

  9. 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.

  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. The Evidence for Increased L1 Activity in the Site of Human Adult Brain Neurogenesis

    PubMed Central

    Kurnosov, Alexey A.; Ustyugova, Svetlana V.; Nazarov, Vadim I.; Minervina, Anastasia A.; Komkov, Alexander Yu.; Shugay, Mikhail; Pogorelyy, Mikhail V.; Khodosevich, Konstantin V.; Mamedov, Ilgar Z.; Lebedev, Yuri B.

    2015-01-01

    Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus—the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory. PMID:25689626

  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. Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging

    PubMed Central

    Sun, Felicia W.; Stepanovic, Michael R.; Andreano, Joseph

    2016-01-01

    Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with

  14. Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3.

    PubMed

    Zou, Zhaoxia; Yin, Yufang; Lin, Jenny; Hsu, Li-Chen J; Brandon, Vanessa L; Yang, Fan; Jove, Richard; Jandial, Rahul; Li, Gang; Chen, Mike Y

    2016-05-01

    OBJECT Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODS Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTS The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 -/- cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth. CONCLUSIONS The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents. PMID:26544779

  15. Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3.

    PubMed

    Zou, Zhaoxia; Yin, Yufang; Lin, Jenny; Hsu, Li-Chen J; Brandon, Vanessa L; Yang, Fan; Jove, Richard; Jandial, Rahul; Li, Gang; Chen, Mike Y

    2016-05-01

    OBJECT Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODS Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTS The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 -/- cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth. CONCLUSIONS The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents.

  16. 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'.

  17. Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

    PubMed Central

    Sato, João Ricardo; Hoexter, Marcelo Queiroz; Castellanos, Xavier Francisco; Rohde, Luis A.

    2012-01-01

    Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits. PMID:23049834

  18. 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.

  19. 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

  20. 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

  1. Expression of dominant negative cadherin in the adult mouse brain modifies rearing behavior.

    PubMed

    Edsbagge, Josefina; Zhu, Shunwei; Xiao, Min-Yi; Wigström, Holger; Mohammed, Abdul H; Semb, Henrik

    2004-03-01

    The cadherin superfamily of cell-cell adhesion molecules (CAM) are crucial regulators of morphogenesis and axonal guidance during development of the nervous system and have been suggested to play important roles in neural plasticity of the brain. To study the latter, we created a mouse model that expressed a dominant negative classical cadherin in the brain of adult mice. The mice were tested for spontaneous motor activity and exploratory behavior in the open field, anxiety in the plus-maze, and spatial learning and memory in the water-T maze. Mice expressing the dominant negative cadherin displayed reduced rearing behavior, but no change in motor activity, in the open field, indicating deficits in exploratory behavior. In the water maze, animals expressing the mutant cadherin showed normal escape latencies and were indistinguishable from control littermates. Similarly, LTP in hippocampal slices of cadherin mutant and control mice were indistinguishable. These findings demonstrate intact spatial learning in mice expressing a dominant negative cadherin but altered rearing behavior, suggesting the involvement of classical cadherins in mechanisms mediating rearing behavior.

  2. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    PubMed

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

  3. Positron Emission Tomography of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome

    PubMed Central

    Nelson, Linda D.; Siddarth, Prabha; Kepe, Vladimir; Scheibel, Kevin E.; Huang, S. C.; Barrio, Jorge R.; Small, Gary W.

    2012-01-01

    Objectives To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18–labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([18F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [18F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants. Design Cross-sectional clinical study. Participants Volunteer sample of 19 persons with Down syndrome without dementia (mean age, 36.7 years), 10 patients with Alzheimer disease (mean age, 66.5 years), and 10 controls (mean age, 43.8 years). Main Outcome Measures Binding of [18F]FDDNP in brain regions of interest, including the parietal, medial temporal, lateral temporal, and frontal lobes and posterior cingulate gyrus, and the average of all regions (global binding). Results The [18F]FDDNP binding values were higher in all brain regions in the Down syndrome group than in controls. Compared with the Alzheimer disease group, the Down syndrome group had higher [18F]FDDNP binding values in the parietal and frontal regions, whereas binding levels in other regions were comparable. Within the Down syndrome group, age correlated with [18F]FDDNP binding values in all regions except the posterior cingulate, and several measures of behavioral dysfunction showed positive correlations with global, frontal, parietal, and posterior cingulate [18F]FDDNP binding. Conclusions Consistent with neuropathological findings from postmortem studies, [18F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group. The positive associations between [18F]FDDNP binding levels and age as well as behavioral dysfunction in Down syndrome are consistent with the age-related progression of Alzheimer

  4. 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)…

  5. 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…

  6. The effects of cognitive-behavioral therapy on intrinsic functional brain networks in adults with attention-deficit/hyperactivity disorder.

    PubMed

    Wang, Xiaoli; Cao, Qingjiu; Wang, Jinhui; Wu, Zhaomin; Wang, Peng; Sun, Li; Cai, Taisheng; Wang, Yufeng

    2016-01-01

    Cognitive-behavioral therapy (CBT) is an efficacious psychological treatment for adults with attention-deficit/hyperactivity disorder (ADHD), but the neural processes underlying the benefits of CBT are not well understood. This study aims to unravel psychosocial mechanisms for treatment ADHD by exploring the effects of CBT on functional brain networks. Ten adults with ADHD were enrolled and resting-state functional magnetic resonance imaging scans were acquired before and after a 12-session CBT. Twelve age- and gender-matched healthy controls were also scanned. We constructed whole-brain functional connectivity networks using graph-theory approaches and further computed the changes of regional functional connectivity strength (rFCS) between pre- and post-CBT in ADHD for measuring the effects of CBT. The results showed that rFCS was increased in the fronto-parietal network and cerebellum, the brain regions that were most often affected by medication, in adults with ADHD following CBT. Furthermore, the enhanced functional coupling between bilateral superior parietal gyrus was positively correlated with the improvement of ADHD symptoms following CBT. Together, these findings provide evidence that CBT can selectively modulate the intrinsic network connectivity in the fronto-parietal network and cerebellum and suggest that the CBT may share common brain mechanism with the pharmacology in adults with ADHD.

  7. 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…

  8. Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults.

    PubMed

    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.

  9. 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.

  10. Expression of the AMF/neuroleukin receptor in developing and adult brain cerebellum.

    PubMed

    Leclerc, N; Vallée, A; Nabi, I R

    2000-06-01

    The peptide sequence of autocrine motility factor (AMF), a tumor secreted cytokine that induces cell motility, corresponds to that of the previously identified cytokine/enzyme, neuroleukin/glucose-6-phosphate isomerase. Neuroleukin is a neurotrophic factor that promotes neuronal survival and sprouting at the neuromuscular junction. The AMF receptor (AMF-R) has been identified and shown to be highly expressed in malignant tumors with minimal expression in adjacent normal tissue. Neuroleukin mRNA is highly expressed in the cerebellum and we therefore undertook a developmental study of AMF-R expression in rat cerebellum. As determined by immunoblot, AMF-R is expressed at equivalent high levels in brain and cerebellum of postnatal day 5 (P5) and 12 (P12) rats and at significantly reduced levels in the adult. Coimmunofluorescence studies with MAP-2 and gamma-actin revealed that at P12, AMF-R was mainly localized to Purkinje and granule cells. Moreover, the premigratory cells of the external granular layer were also immunoreactive for AMF-R suggesting a role for AMF-R in granule cell migration during cerebellar development in the first two weeks after birth. In the adult, AMF-R distribution was similar to P12, although weaker, and was localized to Purkinje and granule cells. AMF-R labeling of GFAP positive glial processes could not be detected in cerebellar sections although in cerebellar primary cultures, both neurons and glial cells were labeled for AMF-R. In neurons, AMF-R labeling was present in the cell body, neurites and growth cones. These data indicate that regulation of the neurotrophic function of neuroleukin might be regulated spatially and temporally by expression of its receptor, AMF-R, in developing and adult cerebellum.

  11. Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury

    PubMed Central

    Villasana, Laura E.; Kim, Kristine N.

    2015-01-01

    Abstract Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology, and synaptic integration of new hippocampal neurons after a controlled cortical impact (CCI) injury model of TBI. To label TBI-induced newborn neurons, we used 2-month-old POMC-EGFP mice, which transiently and specifically express EGFP in immature hippocampal neurons, and doublecortin-CreERT2 transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, to permanently pulse-label a cohort of adult-born hippocampal neurons. TBI increased the generation, outward migration, and dendritic complexity of neurons born during post-traumatic neurogenesis. Cells born after TBI had profound alterations in their dendritic structure, with increased dendritic branching proximal to the soma and widely splayed dendritic branches. These changes were apparent during early dendritic outgrowth and persisted as these cells matured. Whole-cell recordings from neurons generated during post-traumatic neurogenesis demonstrate that they are excitable and functionally integrate into the hippocampal circuit. However, despite their dramatic morphologic abnormalities, we found no differences in the rate of their electrophysiological maturation, or their overall degree of synaptic integration when compared to age-matched adult-born cells from sham mice. Our results suggest that cells born after TBI participate in information processing, and receive an apparently normal balance of excitatory and inhibitory inputs. However, TBI-induced changes in their anatomic localization and dendritic projection patterns could result in maladaptive network properties. PMID:26478908

  12. 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

  13. 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

  14. Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain.

    PubMed

    Ramos-Moreno, Tania; Galazo, Maria J; Porrero, Cesar; Martínez-Cerdeño, Verónica; Clascá, Francisco

    2006-01-01

    Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.

  15. Longitudinal alterations to brain function, structure, and cognitive performance in healthy older adults: A fMRI-DTI study.

    PubMed

    Hakun, Jonathan G; Zhu, Zude; Brown, Christopher A; Johnson, Nathan F; Gold, Brian T

    2015-05-01

    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.

  16. 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

  17. PCNA immunoreactivity revealing normal proliferative activity in the brain of an adult Elasmobranch, Torpedo marmorata.

    PubMed

    Margotta, Vito

    2007-01-01

    The brain of adult heterothermic vertebrates can be already provided of quiescent cells, scattered ("matrix cells") and/or clustered ("matrix areas"). These typical cells, in some regions located at or near ventricular surfaces and at peri-ependymal layers, in other territories populating their framework, maintain some embryonic properties and are responsible of normal or variously experimentally induced proliferative activities. On these topics there are a great number of reports concerning Teleostean Osteichthyes, Urodele and Anuran Amphibians, Lacertilian Reptiles. At the contrary, only few are the contributions regarding the Petromyzontidae. Involving an immunocytochemical marker, the Proliferating Cell Nuclear Antigen (PCNA), revealing proliferative events, in the last years we have undertaken a reappraisal focused on these encephalic performances in normal adult poikilothermal vertebrates. To provide a valid comparison between our results and the literature data, our choice of the specimens was based on the desire to employ organisms belonging to the same or phylogenetically close species used by previous Authors in similar studies. In our immunocytochemical panorama there is a substantial agreement between our contributions and bibliographic references concerning natural encephalic proliferative phenomena in these vertebrates. At this point of our study, the last missing piece was represented by the Chondrichthyes about which the literature data are lacking. In order to fill this gap, the aim of the present research is to investigate, involving the same PCNA test, whether proliferative events also persist in the brain of adult cartilaginous fishes. The immunostaining images obtained in the Elasmo branch Torpedo marmorata, well-known for the emission of high electrical discharges, exhibit undifferentiated cells in relationship with the ependymal epithelium lining the cavities of all cerebral districts; some other neuroblasts are scattered in the mesencephalic

  18. 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.

  19. 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

  20. Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

    PubMed Central

    Gugliotta, Marinella; Rolfe, Andrew; Reid, Wendy; McQuiston, A. Rory; Hu, Wenhui; Young, Harold

    2011-01-01

    Abstract Multipotent neural stem/progenitor cells (NS/NPCs) that are capable of generating neurons and glia offer enormous potential for treating neurological diseases. Adult NS/NPCs that reside in the mature mammalian brain can be isolated and expanded in vitro, and could be a potential source for autologous transplantation to replace cells lost to brain injury or disease. When these cells are transplanted into the normal brain, they can survive and become region-specific cells. However, it has not been reported whether these cells can survive for an extended period and become functional cells in an injured heterotypic environment. In this study, we tested survival, maturation fate, and electrophysiological properties of adult NS/NPCs after transplantation into the injured rat brain. NS/NPCs were isolated from the subventricular zone of adult Fisher 344 rats and cultured as a monolayer. Recipient adult Fisher 344 rats were first subjected to a moderate fluid percussive injury. Two days later, cultured NS/NPCs were injected into the injured brain in an area between the white matter tracts and peri-cortical region directly underneath the injury impact. The animals were sacrificed 2 or 4 weeks after transplantation for immunohistochemical staining or patch-clamp recording. We found that transplanted cells survived well at 2 and 4 weeks. Many cells migrated out of the injection site into surrounding areas expressing astrocyte or oligodendrocyte markers. Whole cell patch-clamp recording at 4 weeks showed that transplanted cells possessed typical mature glial cell properties. These data demonstrate that adult NS/NPCs can survive in an injured heterotypic environment for an extended period and become functional cells. PMID:21332258

  1. Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat.

    PubMed

    Fernández-López, David; Faustino, Joel; Daneman, Richard; Zhou, Lu; Lee, Sarah Y; Derugin, Nikita; Wendland, Michael F; Vexler, Zinaida S

    2012-07-11

    The immaturity of the CNS at birth greatly affects injury after stroke but the contribution of the blood-brain barrier (BBB) to the differential response to stroke in adults and neonates is poorly understood. We asked whether the structure and function of the BBB is disrupted differently in neonatal and adult rats by transient middle cerebral artery occlusion. In adult rats, albumin leakage into injured regions was markedly increased during 2-24 h reperfusion but leakage remained low in the neonates. Functional assays employing intravascular tracers in the neonates showed that BBB permeability to both large (70 kDa dextran) and small (3 kDa dextran), gadolinium (III)-diethyltriaminepentaacetic acid tracers remained largely undisturbed 24 h after reperfusion. The profoundly different functional integrity of the BBB was associated with the largely nonoverlapping patterns of regulated genes in endothelial cells purified from injured and uninjured adult and neonatal brain at 24 h (endothelial transcriptome, 31,042 total probe sets). Within significantly regulated 1266 probe sets in injured adults and 361 probe sets in neonates, changes in the gene expression of the basal lamina components, adhesion molecules, the tight junction protein occludin, and matrix metalloproteinase-9 were among the key differences. The protein expression of collagen-IV, laminin, claudin-5, occludin, and zonula occludens protein 1 was also better preserved in neonatal rats. Neutrophil infiltration remained low in acutely injured neonates but neutralization of cytokine-induced neutrophil chemoattractant-1 in the systemic circulation enhanced neutrophil infiltration, BBB permeability, and injury. The markedly more integrant BBB in neonatal brain than in adult brain after acute stroke may have major implications for the treatment of neonatal stroke. PMID:22787045

  2. Coarse coding and discourse comprehension in adults with right hemisphere brain damage

    PubMed Central

    Tompkins, Connie A.; Scharp, Victoria L.; Meigh, Kimberly M.; Fassbinder, Wiltrud

    2009-01-01

    Background Various investigators suggest that some discourse-level comprehension difficulties in adults with right hemisphere brain damage (RHD) have a lexical-semantic basis. As words are processed, the intact right hemisphere arouses and sustains activation of a wide-ranging network of secondary or peripheral meanings and features—a phenomenon dubbed “coarse coding”. Coarse coding impairment has been postulated to underpin some prototypical RHD comprehension deficits, such as difficulties with nonliteral language interpretation, discourse integration, some kinds of inference generation, and recovery when a reinterpretation is needed. To date, however, no studies have addressed the hypothesised link between coarse coding deficit and discourse comprehension in RHD. Aims The current investigation examined whether coarse coding was related to performance on two measures of narrative comprehension in adults with RHD. Methods & Procedures Participants were 32 adults with unilateral RHD from cerebrovascular accident, and 38 adults without brain damage. Coarse coding was operationalised as poor activation of peripheral/weakly related semantic features of words. For the coarse coding assessment, participants listened to spoken sentences that ended in a concrete noun. Each sentence was followed by a spoken target phoneme string. Targets were subordinate semantic features of the sentence-final nouns that were incompatible with their dominant mental representations (e.g., “rotten” for apple). Targets were presented at two post-noun intervals. A lexical decision task was used to gauge both early activation and maintenance of activation of these weakly related semantic features. One of the narrative tasks assessed comprehension of implied main ideas and details, while the other indexed high-level inferencing and integration. Both comprehension tasks were presented auditorily. For all tasks, accuracy of performance was the dependent measure. Correlations were computed

  3. Reading in the brain of children and adults: a meta-analysis of 40 functional magnetic resonance imaging studies.

    PubMed

    Martin, Anna; Schurz, Matthias; Kronbichler, Martin; Richlan, Fabio

    2015-05-01

    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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Influence of environmental stimulation on neurogenesis in the adult insect brain.

    PubMed

    Scotto Lomassese, S; Strambi, C; Strambi, A; Charpin, P; Augier, R; Aouane, A; Cayre, M

    2000-11-15

    Mushroom bodies are the main integrative structures of insect brain. They receive sensory information from the eyes, the palps, and the antennae. In the house cricket, Acheta domesticus, a cluster of mushroom body neuroblasts keeps producing new interneurons during an insect's life span. The aim of the present work is to study the impact of environmental stimuli on mushroom body neurogenesis during adulthood. Crickets were reared either in an enriched environment, where they received complex environmental and congeneric stimulations or isolated in small cages and deprived of most visual, auditory, and olfactory stimuli. They then were injected with a S-phase marker, 5-bromo, 2'-deoxyuridine (BrdU) and sacrificed at different periods of their life. Neurogenesis and cell survival were estimated by counting the number of BrdU-labeled cells in the mushroom bodies. Environmentally enriched crickets were found to have an increased number of newborn cells in their mushroom bodies compared with crickets housed in cages with an impoverished environment. This effect of external factors on neurogenesis seems to be limited to the beginning of imaginal life. Furthermore, no cell loss could be detected among the newborn neurons in either environmental situation, suggesting that cell survival was not affected by the quality of the environment. Considering vertebrate studies which showed that enriched environment increases hippocampal cell survival and improves animal performances in spatial learning tests, we suggest that the increased number of interneurons produced in an integrative brain structure after exposure to enriched environment could contribute to adaptive behavioral performances in adult insects.

  15. Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation.

    PubMed

    Wong-Goodrich, Sarah J E; Pfau, Madeline L; Flores, Catherine T; Fraser, Jennifer A; Williams, Christina L; Jones, Lee W

    2010-11-15

    Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to 4 months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting 1 month after sham or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdUrd) immunolabeling and enzyme-linked immunosorbent assay indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdUrd+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor-1, and occurred despite irradiation-induced elevations in hippocampal proinflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention.

  16. Correlations between Brain Cortical Thickness and Cutaneous Pain Thresholds Are Atypical in Adults with Migraine

    PubMed Central

    Schwedt, Todd J.; Chong, Catherine D.

    2014-01-01

    Background/Objective Migraineurs have atypical pain processing, increased expectations for pain, and hypervigilance for pain. Recent studies identified correlations between brain structure and pain sensation in healthy adults. The objective of this study was to compare cortical thickness-to-pain threshold correlations in migraineurs to healthy controls. We hypothesized that migraineurs would have aberrant relationships between the anatomical neurocorrelates of pain processing and pain thresholds. Methods Pain thresholds to cutaneously applied heat were determined for 31 adult migraineurs and 32 healthy controls. Cortical thickness was determined from magnetic resonance imaging T1-weighted sequences. Regional cortical thickness-to-pain threshold correlations were determined for migraineurs and controls separately using a general linear model whole brain vertex-wise analysis. A pain threshold-by-group interaction analysis was then conducted to estimate regions where migraineurs show alterations in the pain threshold-to-cortical thickness correlations relative to healthy controls. Results Controls had negative correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left posterior cingulate/precuneus, right superior temporal, right inferior parietal, and left inferior temporal regions, and a negative correlation (p<0.01 Monte Carlo corrected) with a left superior temporal/inferior parietal region. Migraineurs had positive correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left superior temporal/inferior parietal, right precuneus, right superior temporal/inferior parietal, and left inferior parietal regions. Cortical thickness-to-pain threshold correlations differed between migraine and control groups (p<0.01 uncorrected) for right superior temporal/inferior parietal, right precentral, left posterior cingulate/precuneus, and right inferior parietal regions and (p<0.01 Monte Carlo corrected) for a left superior

  17. Postnatal day 7 ethanol treatment causes persistent reductions in adult mouse brain volume and cortical neurons with sex specific effects on neurogenesis.

    PubMed

    Coleman, Leon G; Oguz, Ipek; Lee, Joohwi; Styner, Martin; Crews, Fulton T

    2012-09-01

    Ethanol treatment on postnatal day seven (P7) causes robust brain cell death and is a model of late gestational alcohol exposure (Ikonomidou et al., 2000). To investigate the long-term effects of P7 ethanol treatment on adult brain, mice received either two doses of saline or ethanol on P7 (2.5 g/kg, s.c., 2 h apart) and were assessed as adults (P82) for brain volume (using postmortem MRI) and cellular architecture (using immunohistochemistry). Adult mice that received P7 ethanol had reduced MRI total brain volume (4%) with multiple brain regions being reduced in both males and females. Immunohistochemistry indicated reduced frontal cortical parvalbumin immunoreactive (PV + IR) interneurons (18-33%) and reduced Cux1+IR layer II pyramidal neurons (15%) in both sexes. Interestingly, markers of adult hippocampal neurogenesis differed between sexes, with only ethanol treated males showing increased doublecortin and Ki67 expression (52 and 57% respectively) in the dentate gyrus, consistent with increased neurogenesis compared to controls. These findings suggest that P7 ethanol treatment causes persistent reductions in adult brain volume and frontal cortical neurons in both males and females. Increased adult neurogenesis in males, but not females, is consistent with differential adaptive responses to P7 ethanol toxicity between the sexes. One day of ethanol exposure, e.g. P7, causes persistent adult brain dysmorphology.

  18. Transporters of the blood-brain and blood-CSF interfaces in development and in the adult.

    PubMed

    Saunders, Norman R; Daneman, Richard; Dziegielewska, Katarzyna M; Liddelow, Shane A

    2013-01-01

    The protective barriers of the brain provide a complex series of physical and chemical obstacles to movement of macromolecules from the periphery into the central nervous system. Studies on these barriers have been focused on two main research areas: (i) anatomical and physiological descriptions of their properties, including during development where functioning barriers are likely to be important for normal neuronal growth; and (ii), investigations of these barriers during disease and attempts at overcoming their defenses in order to deliver drugs to the central nervous system. Both fields are now advanced by the application of molecular gene expression studies of cerebral endothelia (blood vasculature, site of the blood-brain barrier) and choroid plexus epithelia (site of the blood-cerebrospinal fluid barrier) from developing and adult brains, particularly with respect to solute-linked carriers and other transporters. These new techniques provide a wealth of information on the changing nature of transporters at barrier interfaces during normal development and following disease. This review outlines published findings from transcriptome and qPCR studies of expression of genes coding for transporters in these barriers, with a focus on developing brain. The findings clearly support earlier published physiological data describing specific transport mechanisms across barrier interfaces both in the adult and in particular in the developing brain. PMID:23506907

  19. 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

  20. 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

  1. CPG15 regulates synapse stability in the developing and adult brain.

    PubMed

    Fujino, Tadahiro; Leslie, Jennifer H; Eavri, Ronen; Chen, Jerry L; Lin, Walter C; Flanders, Genevieve H; Borok, Erzsebet; Horvath, Tamas L; Nedivi, Elly

    2011-12-15

    Use-dependent selection of optimal connections is a key feature of neural circuit development and, in the mature brain, underlies functional adaptation, such as is required for learning and memory. Activity patterns guide circuit refinement through selective stabilization or elimination of specific neuronal branches and synapses. The molecular signals that mediate activity-dependent synapse and arbor stabilization and maintenance remain elusive. We report that knockout of the activity-regulated gene cpg15 in mice delays developmental maturation of axonal and dendritic arbors visualized by anterograde tracing and diolistic labeling, respectively. Electrophysiology shows that synaptic maturation is also delayed, and electron microscopy confirms that many dendritic spines initially lack functional synaptic contacts. While circuits eventually develop, in vivo imaging reveals that spine maintenance is compromised in the adult, leading to a gradual attrition in spine numbers. Loss of cpg15 also results in poor learning. cpg15 knockout mice require more trails to learn, but once they learn, memories are retained. Our findings suggest that CPG15 acts to stabilize active synapses on dendritic spines, resulting in selective spine and arbor stabilization and synaptic maturation, and that synapse stabilization mediated by CPG15 is critical for efficient learning. PMID:22190461

  2. LRRK2 is expressed in areas affected by Parkinson's disease in the adult mouse brain.

    PubMed

    Simón-Sánchez, Javier; Herranz-Pérez, Vicente; Olucha-Bordonau, Francisco; Pérez-Tur, Jordi

    2006-02-01

    The leucine-rich repeat kinase 2 (LRRK2) gene was recently found to have multiple mutations that are causative for autosomal dominant inherited Parkinson's disease (PD). Previously, we used Northern blot analysis to show that this gene was expressed in the cerebellum, cerebral cortex, medulla, spinal cord, occipital pole, frontal lobe, temporal lobe and caudate putamen. However, a more comprehensive map of LRRK2 mRNA localization in the central nervous system is still lacking. In this study we have mapped the distribution of the mRNA encoding for LRRK2 using nonradioactive in situ hybridization. We detected a moderate expression of this PD-related gene throughout the adult B2B6 mouse brain. A stronger hybridization signal was observed in deep cerebral cortex layers, superficial cingulate cortex layers, the piriform cortex, hippocampal formation, caudate putamen, substantia nigra, the basolateral and basomedial anterior amygdala nuclei, reticular thalamic nucleus and also in the cerebellar granular cell layer. Given that LRRK2 mRNA is highly enriched in motor systems and also is expressed in other systems, we may conclude that mutations in LRRK2 may affect several motor and nonmotor structures that may play an important role in the development of PD.

  3. Radial glia-mediated up-regulation of somatostatin in the regenerating adult fish brain.

    PubMed

    Zupanc, G K; Clint, S C

    2001-08-31

    Adult teleost fish, Apteronotus leptorhynchus, exhibit an enormous regenerative capability after application of mechanical lesions to the dorsalmost subdivision of the cerebellum, the corpus cerebelli. Restoration of the neural tissue is achieved by a cascade of processes, including the guidance of migrating new neurons to the site of injury by radial glial fibers. These fibers are characterised by the expression of immunoreactive glial fibrillary acidic protein and by several morphological features. Within 12 h following the lesion, the fraction of radial glial fibers expressing the neuropeptide somatostatin (SRIF) dramatically increased from approximately 1%, as found in the intact brain, to roughly 27% 12-24 h post-lesion. Subsequently, the percentage of SRIF-expressing radial glial fibers gradually declined, until it reached background levels at about 10 days following the injury. We hypothesise that the expression of SRIF is related to the generation and/or differentiation of the new neurons produced in response to the lesion, rather than to the later guidance of these cells along their migratory pathway.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Quantitative comparison of CrkL-SH3 binding proteins from embryonic murine brain and liver: Implications for developmental signaling and the quantification of protein species variants in bottom-up proteomics.

    PubMed

    Cheerathodi, Mujeeburahim; Vincent, James J; Ballif, Bryan A

    2015-07-01

    A major aim of proteomics is to comprehensively identify and quantify all protein species variants from a given biological source. However, in spite of its tremendous utility, bottom-up proteomic strategies can do little to provide true quantification of distinct whole protein species variants given its reliance on proteolysis. This is particularly true when molecular size information is lost as in gel-free proteomics. Crk and CrkL comprise a family of adaptor proteins that couple upstream phosphotyrosine signals to downstream effectors by virtue of their SH2 and SH3 domains respectively. Here we compare the identification and quantification of CrkL-SH3 binding partners between embryonic murine brain and liver. We also uncover and quantify tissue-specific variants in CrkL-SH3 binding proteins.

  9. 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

  10. 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

  11. 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.

  12. Cardiovascular risks and brain function: a functional magnetic resonance imaging study of executive function in older adults.

    PubMed

    Chuang, Yi-Fang; Eldreth, Dana; Erickson, Kirk I; Varma, Vijay; Harris, Gregory; Fried, Linda P; Rebok, George W; Tanner, Elizabeth K; Carlson, Michelle C

    2014-06-01

    Cardiovascular (CV) risk factors, such as hypertension, diabetes, and hyperlipidemia are associated with cognitive impairment and risk of dementia in older adults. However, the mechanisms linking them are not clear. This study aims to investigate the association between aggregate CV risk, assessed by the Framingham general cardiovascular risk profile, and functional brain activation in a group of community-dwelling older adults. Sixty participants (mean age: 64.6 years) from the Brain Health Study, a nested study of the Baltimore Experience Corps Trial, underwent functional magnetic resonance imaging using the Flanker task. We found that participants with higher CV risk had greater task-related activation in the left inferior parietal region, and this increased activation was associated with poorer task performance. Our results provide insights into the neural systems underlying the relationship between CV risk and executive function. Increased activation of the inferior parietal region may offer a pathway through which CV risk increases risk for cognitive impairment.

  13. 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

    2015-10-20

    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.

  14. 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

  15. Brain positron emission tomography in splenectomized adults with β-thalassemia intermedia: uncovering yet another covert abnormality.

    PubMed

    Musallam, Khaled M; Nasreddine, Wassim; Beydoun, Ahmad; Hourani, Roula; Hankir, Ahmed; Koussa, Suzanne; Haidar, Mohamad; Taher, Ali T

    2012-02-01

    Covert brain infarction is an emerging concern in patients with β-thalassemia intermedia (TI). We have recently observed a high prevalence (60%) of silent brain infarction on brain magnetic resonance imaging (MRI) in 30 splenectomized adults with TI. In this work, we further evaluate cerebral involvement in the same 30 patients using fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scanning. The median age was 32 years (range, 18-54 years) with a male to female ratio of 13:17. Nineteen patients (63.3%) had evidence of decreased neuronal function on PET-CT. Involvement was mostly left sided, multiple, and most commonly in the temporal and parietal lobes. Elevated liver iron concentration, beyond 15 mg Fe/g dry weight, characterized patients with decreased neuronal function. The concordance rate between brain MRI and PET-CT for the detection of brain abnormality was only 36.7% (Kappa 0.056, P = 0.757), highlighting that both modalities reveal different types of brain pathology. Decreased neuronal function is a common finding in patients with TI and is associated with iron overload. Moreover, the addition of PET-CT to MRI identifies a greater proportion of TI patients with silent neuroimaging abnormalities.

  16. 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

  17. 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

  18. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    PubMed

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  19. 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

  20. Primary adult human astrocytes as an ex vivo vehicle for beta-glucuronidase delivery in the brain.

    PubMed

    Serguera, C; Sarkis, C; Ridet, J L; Colin, P; Moullier, P; Mallet, J

    2001-06-01

    Astrocytes are a good candidate cell type for brain transplantation: They are endogenous to the CNS, they have efficient secretory machinery, and they play a major role in neuronal support. We assessed the potential of genetically modified primary adult human astrocytes as vehicles for the delivery of secreted molecules in the mammalian CNS. We report that such cells can be efficiently transduced by a recombinant adenoviral vector carrying the human beta-glucuronidase cDNA (Ad/CMV*beta-glu) and that the transduced astrocytes produce large amounts of the enzyme. Released beta-glucuronidase could be captured, in vitro, by primary neurons and astrocytes and by a neuroblastoma cell line and beta-glucuronidase-deficient fibroblasts. Following grafting into the mouse striatum, adult human astrocytes survived and expressed the transgene for at least 8 weeks. Moreover, the dosage of beta-glucuronidase activity within the grafted brains revealed high enzymatic levels at a long distance from the graft. These experiments document the grafting of engineered primary adult human astrocytes, allowing the release of a secreted therapeutic factor throughout the brain.

  1. 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.

  2. 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

  3. Distribution of APGWamide-immunoreactivity in the brain and reproductive organs of adult pygmy squid, Idiosepius pygmaeus.

    PubMed

    Sirinupong, P; Suwanjarat, J; van Minnen, J

    2011-12-01

    The neuropeptide APGWamide is involved in the control of the reproductive behavior in molluscs. Using immunocytochemistry, we investigated the distribution of APGWa-immunoreactive neurons in the brain and reproductive organs of adult male and female specimen of Idiosepius pygmaeus. The study showed that the APGWamide-immunoreactive neurons and fibers are localized in the dorsal basal and vertical lobes of the supraesophageal mass, the palliovisceral lobe of the posterior subesophageal mass and olfactory lobe of the optic tract in male brains, with the highest number of APGWamide-immunoreactive neurons in the palliovisceral and olfactory lobes. In females, only the palliovisceral and olfactory lobes contained APGWa-immunoreactive neurons. The number of APGWamide-immunoreactive neurons in male I. pygmaeus brain is significantly higher than in females. Furthermore, APGWamide-immunoreactive fibers are localized exclusively in male reproductive organs and mantle muscles. Together these data suggest a role for APGW-amide in the control of male reproduction.

  4. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    PubMed

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all P<0.05). Multivariate analysis revealed that more MVPA was associated with less brain atrophy, even after adjustment for WML (β=-0.126, P=0.015), but LPA was not (β=-0.102, P=0.136). Our study revealed that objectively measured physical activity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health.

  5. Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain.

    PubMed

    Han, Jinju; Kim, Hyung Joon; Schafer, Simon T; Paquola, Apua; Clemenson, Gregory D; Toda, Tomohisa; Oh, Jinseo; Pankonin, Aimee R; Lee, Bo Suk; Johnston, Stephen T; Sarkar, Anindita; Denli, Ahmet M; Gage, Fred H

    2016-07-01

    Altered microRNA profiles have been implicated in human brain disorders. However, the functional contribution of individual microRNAs to neuronal development and function is largely unknown. Here, we report biological functions for miR-19 in adult neurogenesis. We determined that miR-19 is enriched in neural progenitor cells (NPCs) and downregulated during neuronal development in the adult hippocampus. By manipulating miR-19 in NPCs for gain- and loss-of-function studies, we discovered that miR-19 regulates cell migration by directly targeting Rapgef2. Concordantly, dysregulation of miR-19 in NPCs alters the positioning of newborn neurons in the adult brain. Furthermore, we found abnormal expression of miR-19 in human NPCs generated from schizophrenic patient-derived induced pluripotent stem cells (iPSCs) that have been described as displaying aberrant migration. Our study demonstrates the significance of posttranscriptional gene regulation by miR-19 in preventing the irregular migration of adult-born neurons that may contribute to the etiology of schizophrenia. PMID:27387650

  6. 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

  7. Deficit in switching between functional brain networks underlies the impact of multitasking on working memory in older adults.

    PubMed

    Clapp, Wesley C; Rubens, Michael T; Sabharwal, Jasdeep; Gazzaley, Adam

    2011-04-26

    Multitasking negatively influences the retention of information over brief periods of time. This impact of interference on working memory is exacerbated with normal aging. We used functional MRI to investigate the neural basis by which an interruption is more disruptive to working memory performance in older individuals. Younger and older adults engaged in delayed recognition tasks both with and without interruption by a secondary task. Behavioral analysis revealed that working memory performance was more impaired by interruptions in older compared with younger adults. Functional connectivity analyses showed that when interrupted, older adults disengaged from a memory maintenance network and reallocated attentional resources toward the interrupting stimulus in a manner consistent with younger adults. However, unlike younger individuals, older adults failed to both disengage from the interruption and reestablish functional connections associated with the disrupted memory network. These results suggest that multitasking leads to more significant working memory disruption in older adults because of an interruption recovery failure, manifest as a deficient ability to dynamically switch between functional brain networks.

  8. 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

  9. Peripheral Nerve Damage Facilitates Functional Innervation of Brain Grafts in Adult Sensory Cortex

    NASA Astrophysics Data System (ADS)

    Ebner, Ford F.; Erzurumlu, Reha S.; Lee, Stefan M.

    1989-01-01

    The neuralb pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting ``conditions'' or ``primes'' the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis.

  10. Susceptibility of juvenile and adult blood–brain barrier to endothelin-1: regulation of P-glycoprotein and breast cancer resistance protein expression and transport activity

    PubMed Central

    2012-01-01

    Background P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) play a critical role in keeping neurotoxic substances from entering the brain. We and others have previously reported an impact of inflammation on the regulation of adult blood–brain barrier (BBB) efflux transporters. However, studies in children have not been done. From the pediatric clinical perspective, it is important to understand how the central nervous system (CNS) and BBB drug efflux transporters differ in childhood from those of adults under normal and inflammatory conditions. Therefore, we examined and compared the regulation of P-gp and BCRP expression and transport activity in young and adult BBB and investigated the molecular mechanisms underlying inflammatory responses. Methods Rats at postnatal day (P) P21 and P84, corresponding to the juvenile and adult stages of human brain maturation, respectively, were treated with endothelin-1 (ET-1) given by the intracerebroventricular (icv) route. Twenty-four hours later, we measured P-gp and BCRP protein expression in isolated brain capillary by immunoblotting as well as by transport activity in vivo by measuring the unbound drug partitioning coefficient of the brain (Kp,uu,brain) of known efflux transporter substrates administered intravenously. Glial activation was measured by immunohistochemistry. The release of cytokines/chemokines (interleukins-1α, 1-β (IL-1β), -6 (IL-6), -10 (IL-10), monocyte chemoattractant protein (MCP-1/CCL2), fractalkine and tissue inhibitor of metalloproteinases-1 (TIMP-1)) were simultaneously measured in brain and serum samples using the Agilent Technology cytokine microarray. Results We found that juvenile and adult BBBs exhibited similar P-gp and BCRP transport activities in the normal physiological conditions. However, long-term exposure of the juvenile brain to low-dose of ET-1 did not change BBB P-gp transport activity but tended to decrease BCRP transport activity in the juvenile brain, while a

  11. 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)

  12. Distribution and characterization of doublecortin-expressing cells and fibers in the brain of the adult pigeon (Columba livia).

    PubMed

    Melleu, F F; Santos, T S; Lino-de-Oliveira, C; Marino-Neto, J

    2013-01-01

    Doublecortin (DCX) is a microtubule-associated protein essential for the migration of immature neurons in the developing and adult vertebrate brain. Herein, the distribution of DCX-immunoreactive (DCX-ir) cells in the prosencephalon of the adult pigeon (Columba livia) is described, in order to collect the evidence of their immature neural phenotype and to investigate their putative place of origin. Bipolar and multipolar DCX-ir cells were observed to be widespread throughout the parenchyma of the adult pigeon forebrain. Small, bipolar and fusiform DCX-ir cells were especially concentrated at the tips of the lateral walls of the lateral ventricles (VZ) and sparsely distributed in the remaining ependyma. Multipolar DCX-ir cells populated the pallial regions. None of these DCX-ir cells seemed to co-express NeuN or GFAP, suggesting that they were immature neurons. Two different migratory-like routes of DCX-ir cells from the VZ toward different targets in the parenchyma were putatively identified: (i) rostral migratory-like bundle; and (ii) lateral migratory-like bundle. In addition, pial surface bundles and intra-ependymal fascicles were also observed. Pigeons treated with 5-bromo-desoxyuridine (BrdU, 3 intraperitoneal injections of 100mg/kg 2h apart, sacrificed 2h after last injection) displayed BrdU-immunoreactive cells (BrdU-ir) in VZ and ependyma whereas the parenchyma was free of such cells. Despite the regional overlapping, there was no evidence of double-labeling between BrdU and DCX. Therefore, the VZ in the brain of adult pigeons seems to have rapidly dividing cells as putative progenitors of newborn neurons populating the forebrain. The distribution of the newborn neurons in the avian prosencephalon and their migration pathways appear to be larger than in mammals, suggesting that the morphological turnover of forebrain circuits is an important mechanism for brain plasticity in avian species during adulthood.

  13. A different story on “Theory of Mind” deficit in adults with right hemisphere brain damage

    PubMed Central

    Tompkins, Conn