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Sample records for adult rat neural

  1. Altered differentiation of CNS neural progenitor cells after transplantation into the injured adult rat spinal cord.

    PubMed

    Onifer, S M; Cannon, A B; Whittemore, S R

    1997-01-01

    Denervation of CNS neurons and peripheral organs is a consequence of traumatic SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy for reinnervating these targets. Neural progenitor cell lines are being investigated as alternates to embryonic CNS neurons. RN33B is an immortalized neural progenitor cell line derived from embryonic rat raphe nuclei following infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen. Transplantation studies have shown that local epigenetic signals in intact or partially neuron-depleted adult rat hippocampal formation or striatum direct RN33B cell differentiation to complex multipolar morphologies resembling endogenous neurons. After transplantation into neuron-depleted regions of the hippocampal formation or striatum, RN33B cells were relatively undifferentiated or differentiated with bipolar morphologies. The present study examines RN33B cell differentiation after transplantation into normal spinal cord and under different lesion conditions. Adult rats underwent either unilateral lesion of lumbar spinal neurons by intraspinal injection of kainic acid or complete transection at the T10 spinal segment. Neonatal rats underwent either unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B cells were transplanted into the lumbar enlargement of injured and age-matched normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells were found throughout normal rat gray matter. In contrast, only bipolar RN33B cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or transection rats. These observations suggest that RN33B cell multipolar morphological differentiation in normal adult spinal cord is mediated by direct cell-cell interaction through surface molecules on endogenous neurons and may be suppressed by molecules released after SCI

  2. Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord

    PubMed Central

    Yan, Jun; Xu, Leyan; Welsh, Annie M; Hatfield, Glen; Hazel, Thomas; Johe, Karl; Koliatsos, Vassilis E

    2007-01-01

    Background Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC) transplants have shown either poor differentiation or a preferential choice of glial lineages. Methods and Findings In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. Conclusions NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major challenges remain

  3. Folic acid in combination with adult neural stem cells for the treatment of spinal cord injury in rats

    PubMed Central

    Zhang, Chen; Shen, Lin

    2015-01-01

    Purpose: To observe the therapeutic effect of folic acid in combination with adult neural stem cells on spinal cord injury and to investigate the possible mechanism. Methods: A total of 120 Wistar rats were randomly assigned to six groups: normal, model, sham-surgery, folic acid injection, adult neural stem cell transplantation, and combination (folic acid injection + adult neural stem cells transplantation) groups. Morphology of neural stem cells was observed by inverted microscopy. Expression of CD105, CD45, CD44, and CD29 were detected by flow cytometry; expression of neuron-specific enolase and glial fibrillary acidic protein were determined by immunofluorescence. Motor coordination and integration capabilities were assessed using BBB scores; Morphology of spinal cord tissues was observed by hematoxylin-eosin staining and 5-bromodeoxyuridine immunohistochemistry. GDNF, BDNF and NT-3 expression in spinal cord tissues were determined by ELISA; while expression of the apoptosis-related proteins BCL-2, Bax and caspase-3 was detected using western blotting. Results: Flow cytometry showed that the isolated cells were positive for CD44 and CD29 and negative for CD105 and CD45. Combination treatment significantly improved the behavior of model rats with spinal cord injury, attenuated inflammatory reaction of spinal cord tissues, restored injured nerve cells, and increased expression of GDNF, BDNF and NT-3 in spinal cord tissues, up regulated BCL-2 expression, and down regulated Bax and caspase-3 expression. Conclusions: Folic acid in combination with adult neural stem cells significantly improved nerve function and plays a key role in maintaining microenvironment homeostasis in the neurons of rats with spinal cord injury. PMID:26379837

  4. Electroacupuncture upregulates ERK signaling pathways and promotes adult hippocampal neural progenitors proliferation in a rat model of depression

    PubMed Central

    2013-01-01

    Background In this study, we investigate the proliferation of adult neural stem cells (NSCs) in a chronic unpredictable stress (CUS) rat model of depression, the effects of electroacupunture (EA) on depressive-like symptoms and the corresponding signaling pathways. Methods SD rats were subjected to 4 weeks of CUS to induce depressive-like behaviors. EA was performed at the Du-20 (Bai-Hui) and GB-34 (Yang-Ling-Quan) acupoints. Rats were injected with BrdU and the brains were cut into sections. Double-labeling with BrdU/Sox2 and p-ERK/Nestin was performed to demonstrate the in vivo proliferation of adult NSCs in hippocampus and ERK activation in NSCs. Hippocampal microdialysates of different groups were collected to observe the in vitro effects on NSCs. Results After 8 treatments, EA generated a clear antidepressant effect on the stressed rats and promoted the NSC proliferation. ERK activation might be involved in the antidepressant-like effects of EA treatment. Hippocampal microdialysates from EA-treated stressed rats influenced NSCs to form larger neural spheres and exhibit higher p-ERK level in vitro, compared to the untreated stressed rats. Meanwhile, the antidepressant-like effects of EA involved contribution from both acupoint specificity and electrical stimulus. Conclusions EA might interfere with the hippocampal microenvironment and enhance the activation of ERK signaling pathways. This could mediate, at least in part, the beneficial effects of EA on NSC proliferation and depressive-like behaviors. PMID:24165147

  5. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

    PubMed

    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model. PMID:25479965

  6. Temporal Response of Endogenous Neural Progenitor Cells Following Injury to the Adult Rat Spinal Cord

    PubMed Central

    Mao, Yilin; Mathews, Kathryn; Gorrie, Catherine A.

    2016-01-01

    A pool of endogenous neural progenitor cells (NPCs) found in the ependymal layer and the sub-ependymal area of the spinal cord are reported to upregulate Nestin in response to traumatic spinal cord injury (SCI). These cells could potentially be manipulated within a critical time period offering an innovative approach to the repair of SCI. However, little is known about the temporal response of endogenous NPCs following SCI. This study used a mild contusion injury in rat spinal cord and immunohistochemistry to determine the temporal response of ependymal NPCs following injury and their correlation to astrocyte activation at the lesion edge. The results from the study demonstrated that Nestin staining intensity at the central canal peaked at 24 h post-injury and then gradually declined over time. Reactive astrocytes double labeled by Nestin and glial fibrillary acidic protein (GFAP) were found at the lesion edge and commenced to form the glial scar from 1 week after injury. We conclude that the critical time period for manipulating endogenous NPCs following a spinal cod injury in rats is between 24 h when Nestin expression in ependymal cells is increased and 1 week when astrocytes are activated in large numbers. PMID:27013972

  7. Cocaine Sensitization Increases Kyphosis and Modulates Neural Activity in Adult Nulliparous Rats

    PubMed Central

    Nephew, Benjamin C.; Caffrey, Martha K.; Felix-Ortiz, Ada C.; Febo, Marcelo

    2012-01-01

    Although data from both animals and humans suggests that adult cocaine use can have long term effects on behavior, it is unknown if prior cocaine use affects future maternal behavior in nulliparous females. In the current study, cocaine or saline was administered to adult female rats for 10 days, the animals were withdrawn from cocaine for 7 days, and the females were then exposed to donor pups to induce the expression of maternal behavior. Nulliparous females sensitized to cocaine were more likely to retrieve pups, spent more time caring for the pups, and were more likely to express full maternal behavior on day 8 of pup exposure. The fMRI data revealed significant effects of pup exposure in the hippocampal CA1 region, and effects of cocaine in the anterior thalamus and periaqueductal gray. Prior adult cocaine use may have lasting effects on offspring care, and this effect is not dependent on pup mediated effects or the endocrine changes of gestation and lactation. The present findings provide support for the hypothesis that maternal motivation to exhibit maternal behavior is enhanced by prior cocaine sensitization, possibly due to cross sensitization between cocaine and the natural reward of maternal behavior. PMID:24371520

  8. High neuronal/astroglial differentiation plasticity of adult rat hippocampal neural stem/progenitor cells in response to the effects of embryonic and adult cerebrospinal fluids

    PubMed Central

    Peirouvi, T.; Yekani, F.; Azarnia, M.; Massumi, M.

    2015-01-01

    Hippocampal neural stem/progenitor cells (hipp-NS/PCs) of the adult mammalian brain are important sources of neuronal and gial cell production. In this study, the main goal is to investigate the plasticity of these cells in neuronal/astroglial differentiations. To this end, the differentiation of the hipp-NS/PCs isolated from 3-month-old Wistar rats was investigated in response to the embryonic cerebrospinal fluid (E-CSF) including E13.5, E17-CSF and the adult cerebrospinal fluid (A-CSF), all extracted from rats. CSF samples were selected based on their effects on cell behavioral parameters. Primary cell culture was performed in the presence of either normal or high levels of KCL in a culture medium. High levels of KCL cause cell depolarization, and thus the activation of quiescent NSCs. Results from immunocytochemistry (ICC) and semi-quantitative RT-PCR (sRT-PCR) techniques showed that in E-CSF-treated groups, neuronal differentiation increased (E17>E13.5). In contrast, A-CSF decreased and increased neuronal and astroglial differentiations, respectively. Cell survivability and/or proliferation (S/P), evaluated by an MTT assay, increased by E13.5 CSF, but decreased by both E17 CSF and A-CSF. Based on the results, it is finally concluded that adult rat hippocampal proliferative cells are not restricted progenitors but rather show high plasticity in neuronal/astroglial differentiation according to the effects of CSF samples. In addition, using high concentrations of KCL in the primary cell culture led to an increase in the number of NSCs, which in turn resulted in the increase in neuronal or astroglial differentiations after CSF treatment. PMID:27175157

  9. Chronic cocaine exposure impairs progenitor proliferation but spares survival and maturation of neural precursors in adult rat dentate gyrus.

    PubMed

    Domínguez-Escribà, L; Hernández-Rabaza, V; Soriano-Navarro, M; Barcia, J A; Romero, F J; García-Verdugo, J M; Canales, J J

    2006-07-01

    Recent observations indicate that drugs of abuse, including alcohol and opiates, impair adult neurogenesis in the hippocampus. We have studied in rats the impact of cocaine treatment (20 mg/kg, daily, i.p.) on cell proliferation, survival and maturation following short-term (8-day) and long-term (24-day) exposure. Using 5'-bromo-2-deoxyuridine (BrdU) and Ki-67 as mitotic markers at the end of the drug treatments, we found that both short- and long-term cocaine exposures significantly reduced cell proliferation in the dentate gyrus (DG) of the hippocampus. By labelling mitotic cells with BrdU pulses before or during the early stages of the drug treatment, we determined that long-term cocaine exposure did not affect the survival of newly generated cells. In register with this finding, cocaine chronic exposure did not increase the number of apoptotic cells labelled by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling). Using doublecortin (DCX) immunocytochemistry and electron microscopy, we next examined the effects of cocaine exposure on the maturation of the neural precursors and on synaptic output to CA3. DCX immunocytochemistry showed that immature hippocampal cells of rats exposed to cocaine displayed normal arborization patterns and similar degrees of colocalization with BrdU at two different developmental stages. Moreover, cocaine did not produce significant morphological alterations of the mossy fibre projection system to stratum lucidum in the CA3 area of the hippocampus. The results presented demonstrate that chronic cocaine exposure impairs proliferation dynamics in the DG without significantly altering either the survival and growth of immature cells or the structural features of terminal projections to CA3. PMID:16903860

  10. Metabolic neural mapping in neonatal rats

    SciTech Connect

    DiRocco, R.J.; Hall, W.G.

    1981-01-01

    Functional neural mapping by /sup 14/C-deoxyglucose autoradiography in adult rats has shown that increases in neural metabolic rate that are coupled to increased neurophysiological activity are more evident in axon terminals and dendrites than neuron cell bodies. Regions containing architectonically well-defined concentrations of terminals and dendrites (neuropil) have high metabolic rates when the neuropil is physiologically active. In neonatal rats, however, we find that regions containing well-defined groupings of neuron cell bodies have high metabolic rates in /sup 14/C-deoxyglucose autoradiograms. The striking difference between the morphological appearance of /sup 14/C-deoxyglucose autoradiograms obtained from neonatal and adult rats is probably related to developmental changes in morphometric features of differentiating neurons, as well as associated changes in type and locus of neural work performed.

  11. Pharmacology of Ultrasonic Vocalizations in adult Rats: Significance, Call Classification and Neural Substrate

    PubMed Central

    Brudzynski, Stefan M.

    2015-01-01

    Pharmacological studies of emotional arousal and initiation of emotional states in rats measured by their ultrasonic vocalizations are reviewed. It is postulated that emission of vocalizations is an inseparable feature of emotional states and it evolved from mother-infant interaction. Positive emotional states are associated with emission of 50 kHz vocalizations that could be induced by rewarding situations and dopaminergic activation of the nucleus accumbens and are mediated by D1, D2, and partially D3 dopamine receptors. Three biologically significant subtypes of 50 kHz vocalizations have been identified, all expressing positive emotional states: (1) flat calls without frequency modulation that serve as contact calls during social interactions; (2) frequencymodulated calls without trills that signal rewarding and significantly motivated situation; and (3) frequency-modulated calls with trills or trills themselves that are emitted in highly emotional situations associated with intensive affective state. Negative emotional states are associated with emission of 22 kHz vocalizations that could be induced by aversive situations, muscarinic cholinergic activation of limbic areas of medial diencephalon and forebrain, and are mediated by M2 muscarinic receptors. Two biologically significant subtypes of 22 kHz vocalizations have been identified, both expressing negative emotional sates: (1) long calls that serve as alarm calls and signal external danger; and (2) short calls that express a state of discomfort without external danger. The positive and negative states with emission of vocalizations are initiated by two ascending reticular activating subsystems: the mesolimbic dopaminergic subsystem as a specific positive arousal system, and the mesolimbic cholinergic subsystem as a specific negative arousal system. PMID:26411761

  12. A Novel Biopsy Method for Isolating Neural Stem Cells from the Subventricular Zone of the Adult Rat Brain for Autologous Transplantation in CNS Injuries.

    PubMed

    Aligholi, Hadi; Hassanzadeh, Gholamreza; Gorji, Ali; Azari, Hassan

    2016-01-01

    Despite all attempts the problem of regeneration in damaged central nervous system (CNS) has remained challenging due to its cellular complexity and highly organized and sophisticated connections. In this regard, stem cell therapy might serve as a viable therapeutic approach aiming either to support the damaged tissue and hence to reduce the subsequent neurological dysfunctions and impairments or to replace the lost cells and re-establish damaged circuitries. Adult neural stem/progenitor cells (NS/PCs) are one of the outstanding cell sources that can be isolated from the subventricular zone (SVZ) of the lateral ventricles. These cells can differentiate into neurons, astrocytes, and oligodendrocytes. Implanting autologous NS/PCs will greatly benefit the patients by avoiding immune rejection after implantation, better survival, and integration with the host tissue. Developing safe and efficient methods in small animal models will provide us with the opportunity to optimize procedures required to achieve successful human autologous NS/PC transplantation in near future. In this chapter, a highly controlled and safe biopsy method for harvesting stem cell containing tissue from the SVZ of adult rat brain is introduced. Then, isolation and expansion of NS/PCs from harvested specimen as well as the techniques to verify proliferation and differentiation capacity of the resulting NS/PCs are discussed. Finally, a method for assessing the biopsy lesion volume in the brain is described. This safe biopsy method in rat provides a unique tool to study autologous NS/PC transplantation in different CNS injury models. PMID:27604747

  13. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

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

  14. Human Fetal Brain-Derived Neural Stem/Progenitor Cells Grafted into the Adult Epileptic Brain Restrain Seizures in Rat Models of Temporal Lobe Epilepsy

    PubMed Central

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  15. Generalized Potential of Adult Neural Stem Cells

    NASA Astrophysics Data System (ADS)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  16. Proliferation and Glia-Directed Differentiation of Neural Stem Cells in the Subventricular Zone of the Lateral Ventricle and the Migratory Pathway to the Lesions after Cortical Devascularization of Adult Rats

    PubMed Central

    Wan, Feng; Bai, Hua-Jing; Liu, Jun-Qi; Tian, Mo; Wang, Yong-Xue; Niu, Xin; Si, Yin-Chu

    2016-01-01

    We investigated the effects of cortical devascularization on the proliferation, differentiation, and migration of neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricle of adult rats. 60 adult male Wistar rats were randomly divided into control group and devascularized group. At 15 and 30 days after cerebral cortices were devascularized, rats were euthanized and immunohistochemical analysis was performed. The number of PCNA-, Vimentin-, and GFAP-positive cells in the bilateral SVZ of the lateral wall and the superior wall of the lateral ventricles of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). The area density of PCNA-, Vimentin-, and GFAP-positive cells in cortical lesions of 15- and 30-day devascularized groups increased significantly compared with the control group (P < 0.05 and P < 0.01). PCNA-, GFAP-, and Vimentin-positive cells in the SVZ migrated through the rostral migratory stream (RMS), and PCNA-, GFAP-, and Vimentin-positive cells from both the ipsilateral and contralateral dorsolateral SVZ (dl-SVZ) migrated into the corpus callosum (CC) and accumulated, forming a migratory pathway within the CC to the lesioned site. Our study suggested that cortical devascularization induced proliferation, glia-directed differentiation, and migration of NSCs from the SVZ through the RMS or directly to the corpus callosum and finally migrating radially to cortical lesions. This may play a significant role in neural repair. PMID:27294116

  17. Adult neural stem cells stake their ground

    PubMed Central

    Lim, Daniel A.; Alvarez-Buylla, Arturo

    2014-01-01

    The birth of new neurons in the walls of the adult brain lateral ventricles has captured the attention of many neuroscientists for over two decades, yielding key insights into the identity and regulation of neural stem cells (NSCs). In the adult ventricular-subventricular zone (V-SVZ), NSCs are a specialized form of astrocyte that generates several types of neurons for the olfactory bulb. Here we discuss recent findings regarding the unique organization of the V-SVZ NSCs niche, the multiple regulatory controls of neuronal production, the distinct regional identities of adult NSCs, and the epigenetic mechanisms that maintain adult neurogenesis. Understanding how V-SVZ NSCs establish and maintain lifelong neurogenesis continues to provide surprising insights into the cellular and molecular regulation of neural development. PMID:25223700

  18. Neural plasticity in adults with amblyopia.

    PubMed Central

    Levi, D M; Polat, U

    1996-01-01

    Amblyopia is a neuronal abnormality of vision that is often considered irreversible in adults. We found strong and significant improvement of Vernier acuity in human adults with naturally occurring amblyopia following practice. Learning was strongest at the trained orientation and did not transfer to an untrained task (detection), but it did transfer partially to the untrained eye (primarily at the trained orientation). We conclude that this perceptual learning reflects alterations in early neural processes that are localized beyond the site of convergence of the two eyes. Our results suggest a significant degree of plasticity in the visual system of adults with amblyopia. PMID:8692904

  19. Neural stem cell protects aged rat brain from ischemia–reperfusion injury through neurogenesis and angiogenesis

    PubMed Central

    Tang, Yaohui; Wang, Jixian; Lin, Xiaojie; Wang, Liuqing; Shao, Bei; Jin, Kunlin; Wang, Yongting; Yang, Guo-Yuan

    2014-01-01

    Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (P<0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P>0.05) and most of them were differentiated into glial fibrillary acidic protein+ (GFAP+) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (P<0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia. PMID:24714034

  20. Ontogeny of neural circuits underlying spatial memory in the rat

    PubMed Central

    Ainge, James A.; Langston, Rosamund F.

    2012-01-01

    Spatial memory is a well-characterized psychological function in both humans and rodents. The combined computations of a network of systems including place cells in the hippocampus, grid cells in the medial entorhinal cortex and head direction cells found in numerous structures in the brain have been suggested to form the neural instantiation of the cognitive map as first described by Tolman in 1948. However, while our understanding of the neural mechanisms underlying spatial representations in adults is relatively sophisticated, we know substantially less about how this network develops in young animals. In this article we briefly review studies examining the developmental timescale that these systems follow. Electrophysiological recordings from very young rats show that directional information is at adult levels at the outset of navigational experience. The systems supporting allocentric memory, however, take longer to mature. This is consistent with behavioral studies of young rats which show that spatial memory based on head direction develops very early but that allocentric spatial memory takes longer to mature. We go on to report new data demonstrating that memory for associations between objects and their spatial locations is slower to develop than memory for objects alone. This is again consistent with previous reports suggesting that adult like spatial representations have a protracted development in rats and also suggests that the systems involved in processing non-spatial stimuli come online earlier. PMID:22403529

  1. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  2. Interactions between respiratory oscillators in adult rats.

    PubMed

    Huckstepp, Robert Tr; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. PMID:27300271

  3. Age-related changes in neural gap detection thresholds in the rat auditory cortex.

    PubMed

    Zhao, Yin; Xu, Xiaoxiao; He, Juan; Xu, Jinghong; Zhang, Jiping

    2015-02-01

    The ability of the auditory system to resolve sound temporal information is crucial for the understanding of human speech and other species-specific communications. Gap detection threshold, i.e. the ability to detect the shortest duration of a silent interval in a sound, is commonly used to study the auditory temporal resolution. Behavioral studies in humans and rats have shown that normal developing infants have higher gap detection thresholds than adults; however, the underlying neural mechanism is not fully understood. In the present study, we determined and compared the neural gap detection thresholds in the primary auditory cortex of three age groups of rats: the juvenile group (postnatal day 20-30), adult group I (8-10 weeks), and adult group II (28-30 weeks). We found age-related changes in auditory temporal acuity in the auditory cortex, i.e. the proportion of cortical units with short neural gap detection thresholds (< 5 ms) was much lower in juvenile groups compared with that in both adult groups at a constant sound level, and no significant differences in neural gap detection thresholds were found between the two adult groups. In addition, units in the auditory cortex of each group generally showed better gap detection thresholds at higher sound levels than at lower sound levels, exhibiting a level-dependent temporal acuity. These results provided evidence for neural correlates of age-related changes in behavioral gap detection ability during postnatal hearing development. PMID:25388865

  4. DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats

    PubMed Central

    Lee, Heekyung; Kang, Eunchai; GoodSmith, Douglas; Yoon, Do Yeon; Song, Hongjun; Knierim, James J.; Ming, Guo-li; Christian, Kimberly M.

    2015-01-01

    Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. PMID:26161071

  5. DISC1-mediated dysregulation of adult hippocampal neurogenesis in rats.

    PubMed

    Lee, Heekyung; Kang, Eunchai; GoodSmith, Douglas; Yoon, Do Yeon; Song, Hongjun; Knierim, James J; Ming, Guo-Li; Christian, Kimberly M

    2015-01-01

    Adult hippocampal neurogenesis, the constitutive generation of new granule cells in the dentate gyrus of the mature brain, is a robust model of neural development and its dysregulation has been implicated in the pathogenesis of psychiatric and neurological disorders. Previous studies in mice have shown that altered expression of Disrupted-In-Schizophrenia 1 (Disc1), the mouse homolog of a risk gene for major psychiatric disorders, results in several distinct morphological phenotypes during neuronal development. Although there are advantages to using rats over mice for neurophysiological studies, genetic manipulations have not been widely utilized in rat models. Here, we used a retroviral-mediated approach to knockdown DISC1 expression in dividing cells in the rat dentate gyrus and characterized the morphological development of adult-born granule neurons. Consistent with earlier findings in mice, we show that DISC1 knockdown in adult-born dentate granule cells in rats resulted in accelerated dendritic growth, soma hypertrophy, ectopic dendrites, and mispositioning of new granule cells due to overextended migration. Our study thus demonstrates that the Disc1 genetic manipulation approach used in prior mouse studies is feasible in rats and that there is a conserved biological function of this gene across species. Extending gene-based studies of adult hippocampal neurogenesis from mice to rats will allow for the development of additional models that may be more amenable to behavioral and in vivo electrophysiological investigations. These models, in turn, can generate additional insight into the systems-level mechanisms of how risk genes for complex psychiatric disorders may impact adult neurogenesis and hippocampal function. PMID:26161071

  6. Childhood social inequalities influences neural processes in young adult caregiving.

    PubMed

    Kim, Pilyoung; Ho, Shaun S; Evans, Gary W; Liberzon, Israel; Swain, James E

    2015-12-01

    Childhood poverty is associated with harsh parenting with a risk of transmission to the next generation. This prospective study examined the relations between childhood poverty and non-parent adults' neural responses to infant cry sounds. While no main effects of poverty were revealed in contrasts of infant cry versus acoustically matched white noise, a gender by childhood poverty interaction emerged. In females, childhood poverty was associated with increased neural activations in the posterior insula, striatum, calcarine sulcus, hippocampus, and fusiform gyrus, while, in males, childhood poverty was associated with reduced levels of neural responses to infant cry in the same regions. Irrespective of gender, neural activation in these regions was associated with higher levels of annoyance with the cry sound and reduced desire to approach the crying infant. The findings suggest gender differences in neural and emotional responses to infant cry sounds among young adults growing up in poverty. PMID:25981334

  7. Correlation between hippocampal levels of neural, epithelial and inducible NOS and spatial learning skills in rats.

    PubMed

    Gökçek-Saraç, Çiğdem; Karakurt, Serdar; Adalı, Orhan; Jakubowska-Doğru, Ewa

    2012-12-01

    In the present study, to better understand the role of different nitric oxide synthase (NOS) isoforms in hippocampus-dependent forms of learning, we examined the expression of neural, endothelial, and inducible NOS in the hippocampus of young-adult rats classified as "poor" and "good" learners on the basis of their performance in the partially baited 12-arm radial maze. Taking into consideration strain-dependent differences in learning skills and NOS expression, experiments were performed on two different lines of laboratory rats: the inbred Wistar (W) and the outcrossed Wistar/Spraque-Dawley (W/S) line. The hippocampal levels of NOS proteins were assessed by Western Blotting. In the present study, genetically more homogenous W rats showed a slower rate of learning compared to the genetically less homogenous outcrossed W/S rats. The deficient performance in the W rat group compared to outcrossed W/S rats, and in "poor" learners of both groups compared to "good" learners was due to a higher percentage of reference memory errors. The overall NOS levels were significantly higher in W group compared to outcrossed W/S rats. In both rat lines, the rate of learning positively correlated with hippocampal levels of nNOS and negatively correlated with iNOS levels. Hippocampal eNOS levels correlated negatively with animals' performance but only in the W rats. These results suggest that all 3 NOS isoforms are implemented but play different roles in neural signaling. PMID:22909987

  8. In Vivo Neural Tissue Engineering: Cylindrical Biocompatible Hydrogels That Create New Neural Tracts in the Adult Mammalian Brain.

    PubMed

    Clark, Amanda R; Carter, Arrin B; Hager, Lydia E; Price, Elmer M

    2016-08-01

    Individuals with neurodegenerative disorders or brain injury have few treatment options and it has been proposed that endogenous adult neural stem cells can be harnessed to repopulate dysfunctional nonneurogenic regions of the brain. We have accomplished this through the development of rationally designed hydrogel implants that recruit endogenous cells from the adult subventricular zone to create new relatively long tracts of neuroblasts. These implants are biocompatible and biodegradable cylindrical hydrogels consisting of fibrin and immobilized neurotrophic factors. When implanted into rat brain such that the cylinder intersected the migratory path of endogenous neural progenitors (the rostral migratory stream) and led into the nonneurogenic striatum, we observed a robust neurogenic response in the form of migrating neuroblasts with long (>100 μm) complex neurites. The location of these new neural cells in the striatum was directly coincident with the original track of the fibrin implant, which itself had completely degraded, and covered a significant area and distance (>2.5 mm). We also observed a significant number of neuroblasts in the striatal region between the implant track and the lateral ventricle. When these fibrin cylinders were implanted into hemiparkinson rats, correction of parkinsonian behavior was observed. There were no obvious behavioral, inflammatory or tumorigenic sequelae as a consequence of the implants. In conclusion, we have successfully engineered neural tissue in vivo, using neurogenic biomaterials cast into a unique cylindrical architecture. These results represent a novel approach to efficiently induce neurogenesis in a controlled and targeted manner, which may lead toward a new therapeutic modality for neurological disorders. PMID:27295980

  9. Signaling mechanisms regulating adult neural stem cells and neurogenesis

    PubMed Central

    Faigle, Roland; Song, Hongjun

    2012-01-01

    Background Adult neurogenesis occurs throughout life in discrete regions of the mammalian brain and is tightly regulated via both extrinsic environmental influences and intrinsic genetic factors. In recent years, several crucial signaling pathways have been identified in regulating self-renewal, proliferation, and differentiation of neural stem cells, as well as migration and functional integration of developing neurons in the adult brain. Scope of review Here we review our current understanding of signaling mechanisms, including Wnt, notch, sonic hedgehog, growth and neurotrophic factors, bone morphogenetic proteins, neurotransmitters, transcription factors, and epigenetic modulators, and crosstalk between these signaling pathways in the regulation of adult neurogenesis. We also highlight emerging principles in the vastly growing field of adult neural stem cell biology and neural plasticity. Major conclusions Recent methodological advances have enabled the field to identify signaling mechanisms that fine-tune and coordinate neurogenesis in the adult brain, leading to a better characterization of both cell-intrinsic and environmental cues defining the neurogenic niche. Significant questions related to niche cell identity and underlying regulatory mechanisms remain to be fully addressed and will be the focus of future studies. General significance A full understanding of the role and function of individual signaling pathways in regulating neural stem cells and generation and integration of newborn neurons in the adult brain may lead to targeted new therapies for neurological diseases in humans. PMID:22982587

  10. Quantitative analysis of signaling mechanisms controlling adult neural progenitor cell proliferation.

    PubMed

    Schaffer, David V; O'Neill, Analeah; Hochrein, Lisa; McGranahan, Tresa

    2004-01-01

    Tools of systems engineering and signal dynamics were employed to develop a quantitative model of the intracellular signaling systems involved in adult neural stem cell proliferation, based on pathways elucidated in our experimental systems. Neural progenitors isolated from the adult rat hippocampus are dependent on the basic fibroblast growth factor (FGF-2) and extracellular matrix (ECM) proteins. However, the intracellular effects of these stimuli were previously undetermined. We employed chemical inhibitors of known signal transduction molecules to identify important players in the FGF-2/ECM signal cascade, such as the cyclic AMP responsive element binding protein (CREB), protein kinase B/Akt, and several related molecules. Genetic mutants of these proteins were used to confirm their role in adult neural progenitor proliferation. Proliferation was assayed using the incorporation of a thymidine analog to determine cell doubling rate under various stimuli. Such assays have also uncovered novel synergistic signaling between FGF-2 and ECM components. This research is, to our knowledge, the first to elucidate intracellular signaling pathways for adult neural stem cell proliferation. Upon determination of the pertinent intracellular signaling pathways, quantitative immunoblots were employed to examine the dynamics of these systems. These data, as well as enzyme kinetics information from the literature, are being used to parameterize a dynamic mathematical model of progenitor proliferation events induced by FGF-2. This computational model will be used to predict the biochemical and mechanical signaling inputs necessary to achieve a desired proliferative output from the cells, based on specific extracellular stimuli. It is our hope that this essential quantitative understanding will facilitate the use of adult neural stem cells in medical applications. PMID:17271428

  11. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus.

    PubMed

    Li, Yu-Qing; Cheng, Zoey; Wong, Shun

    2016-01-01

    Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation. PMID:27331809

  12. Differential Apoptosis Radiosensitivity of Neural Progenitors in Adult Mouse Hippocampus

    PubMed Central

    Li, Yu-Qing; Cheng, Zoey; Wong, Shun

    2016-01-01

    Mammalian tissue-specific stem cells and progenitors demonstrate differential DNA damage response. Neural progenitors in dentate gyrus of the hippocampus are known to undergo apoptosis after irradiation. Using a mouse model of hippocampal neuronal development, we characterized the apoptosis sensitivity of the different neural progenitor subpopulations in adult mouse dentate gyrus after irradiation. Two different bromodeoxyuridine incorporation paradigms were used for cell fate mapping. We identified two apoptosis sensitive neural progenitor subpopulations after irradiation. The first represented non-proliferative and non-newborn neuroblasts and immature neurons that expressed doublecortin, calretinin or both. The second consisted of proliferative intermediate neural progenitors. The putative radial glia-like neural stem cells or type-1 cells, regardless of proliferation status, were apoptosis resistant after irradiation. There was no evidence of radiation-induced apoptosis in the absence of the Trp53 (p53) gene but absence of Cdkn1a (p21) did not alter the apoptotic response. Upregulation of nuclear p53 was observed in neuroblasts after irradiation. We conclude that adult hippocampal neural progenitors may demonstrate differential p53-dependent apoptosis sensitivity after irradiation. PMID:27331809

  13. Three-dimensional bioprinting of rat embryonic neural cells.

    PubMed

    Lee, Wonhye; Pinckney, Jason; Lee, Vivian; Lee, Jong-Hwan; Fischer, Krisztina; Polio, Samuel; Park, Je-Kyun; Yoo, Seung-Schik

    2009-05-27

    We present a direct cell printing technique to pattern neural cells in a three-dimensional (3D) multilayered collagen gel. A layer of collagen precursor was printed to provide a scaffold for the cells, and the rat embryonic neurons and astrocytes were subsequently printed on the layer. A solution of sodium bicarbonate was applied to the cell containing collagen layer as nebulized aerosols, which allowed the gelation of the collagen. This process was repeated layer-by-layer to construct the 3D cell-hydrogel composites. Upon characterizing the relationship between printing resolutions and the growth of printed neural cells, single/multiple layers of neural cell-hydrogel composites were constructed and cultured. The on-demand capability to print neural cells in a multilayered hydrogel scaffold offers flexibility in generating artificial 3D neural tissue composites. PMID:19369905

  14. Neural representation of dynamic frequency is degraded in older adults.

    PubMed

    Clinard, Christopher G; Cotter, Caitlin M

    2015-05-01

    Older adults, even with clinically normal hearing sensitivity, often report difficulty understanding speech in the presence of background noise. Part of this difficulty may be related to age-related degradations in the neural representation of speech sounds, such as formant transitions. Frequency-following responses (FFRs), which are dependent on phase-locked neural activity, were elicited using sounds consisting of linear frequency sweeps, which may be viewed as simple models of formant transitions. Eighteen adults (ten younger, 22-24 years old, and nine older, 51-67 years old) were tested. FFRs were elicited by tonal sweeps in six conditions. Two directions of frequency change, rising or falling, were used for each of three rates of frequency change. Stimulus-to-response cross correlations revealed that older adults had significantly poorer representation of the tonal sweeps, and that FFRs became poorer for faster rates of change. An additional FFR signal-to-noise ratio analysis based on time windows revealed that across the FFR waveforms and rates of frequency change, older adults had smaller (poorer) signal-to-noise ratios. These results indicate that older adults, even with clinically-normal hearing sensitivity, have degraded phase-locked neural representations of dynamic frequency. PMID:25724819

  15. Adult Palatum as a Novel Source of Neural Crest-Related Stem Cells

    PubMed Central

    Widera, Darius; Zander, Christin; Heidbreder, Meike; Kasperek, Yvonne; Noll, Thomas; Seitz, Oliver; Saldamli, Belma; Sudhoff, Holger; Sader, Robert; Kaltschmidt, Christian; Kaltschmidt, Barbara

    2009-01-01

    Somatic neural and neural crest stem cells are promising sources for cellular therapy of several neurodegenerative diseases. However, because of practical considerations such as inadequate accessibility of the source material, the application of neural crest stem cells is strictly limited. The secondary palate is a highly regenerative and heavily innervated tissue, which develops embryonically under direct contribution of neural crest cells. Here, we describe for the first time the presence of nestin-positive neural crest-related stem cells within Meissner corpuscles and Merkel cell-neurite complexes located in the hard palate of adult Wistar rats. After isolation, palatal neural crest-related stem cells (pNC-SCs) were cultivated in the presence of epidermal growth factor and fibroblast growth factor under serum-free conditions, resulting in large amounts of neurospheres. We used immunocytochemical techniques and reverse transcriptase-polymerase chain reaction to assess the expression profile of pNC-SCs. In addition to the expression of neural crest stem cell markers such as Nestin, Sox2, and p75, we detected the expression of Klf4, Oct4, and c-Myc. pNC-SCs differentiated efficiently into neuronal and glial cells. Finally, we investigated the potential expression of stemness markers within the human palate. We identified expression of stem cell markers nestin and CD133 and the transcription factors needed for reprogramming of somatic cells into pluripotent cells: Sox2, Oct4, Klf4, and c-Myc. These data show that cells isolated from palatal rugae form neurospheres, are highly plastic, and express neural crest stem cell markers. In addition, pNC-SCs may have the ability to differentiate into functional neurons and glial cells, serving as a starting point for therapeutic studies. Stem Cells 2009;27:1899–1910 PMID:19544446

  16. Olig1 expression pattern in neural cells during rat spinal cord development

    PubMed Central

    Qi, Qi; Zhang, Yuxin; Shen, Lin; Wang, Rui; Zhou, Jiansheng; Lü, Hezuo; Hu, Jianguo

    2016-01-01

    Purpose Our purpose was to systematically investigate the expression pattern and role of Olig1 in neural cells during rat spinal cord development. Animals and methods Spinal cord tissues were dissected from Sprague–Dawley rats at embryonic day 14.5 (E14.5) and E18.5, postnatal day 0 (P0), P3, P7, postnatal 2 weeks (P2W), P4W, and adults (more than 2 months after birth), respectively. The expression of Olig1 was determined by Western blot and immunostaining. To observe expression of Olig1 in different neural cell types, a double immunohistochemical staining was performed using antibodies against Olig1 with O4, β-tubulin, glial fibrillary acidic protein (GFAP), and myelin basic protein, respectively. Results The expression of Olig1 protein shows a significant level change in rat spinal cord at different developmental time points. Starting with E14.5, the expression gradually increased and peaked at E18.5. Olig1 decreased gradually from P3 and reached its lowest level on P7. However, interestingly, the Olig1 expression increased again from P2W, until adulthood. Olig1 was coexpressed with O4-positive oligodendrocyte progenitor cells (OPCs) and β-tubulin-positive neurons at all time points during development. Olig1 was also coexpressed transiently with GFAP-positive astrocytes at only E14.5. Olig1 was localized in the cytoplasm of O4- and β-tubulin-positive cells during the period from E14.5 to adult. Conclusion The expression of Olig1 in OPCs and neurons at all time points during development and in astrocytes at E14.5 suggests that Olig1 may play an important role in the generation and maturation of specific neural cells during development of spinal cord. Our results contribute to understanding the mechanism underlying developmental regulation of neural cells by Olig1. PMID:27143892

  17. Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain

    PubMed Central

    Ryu, Sun; Lee, Seung-Hoon; Kim, Seung U.; Yoon, Byung-Woo

    2016-01-01

    Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen NeuN, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ⁄ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke. PMID:27073384

  18. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    SciTech Connect

    Boku, Shuken; Nakagawa, Shin; Takamura, Naoki; Kato, Akiko; Takebayashi, Minoru; Hisaoka-Nakashima, Kazue; Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  19. Adult attachment style modulates neural responses in a mentalizing task.

    PubMed

    Schneider-Hassloff, H; Straube, B; Nuscheler, B; Wemken, G; Kircher, T

    2015-09-10

    Adult attachment style (AAS) is a personality trait that affects social cognition. Behavioral data suggest that AAS influences mentalizing proficiency, i.e. the ability to predict and explain people's behavior with reference to mental states, but the neural correlates are unknown. We here tested how the AAS dimensions "avoidance" (AV) and "anxiety" (ANX) modulate neural correlates of mentalizing. We measured brain activation using functional magnetic resonance imaging (fMRI) in 164 healthy subjects during an interactive mentalizing paradigm (Prisoner's Dilemma Game). AAS was assessed with the Relationship Scales Questionnaire, including the subscales AV and ANX. Our task elicited a strong activation of the mentalizing network, including bilateral precuneus, (anterior, middle, and posterior) cingulate cortices, temporal poles, inferior frontal gyri (IFG), temporoparietal junctions, superior medial frontal gyri as well as right medial orbital frontal gyrus, superior temporal gyrus, middle frontal gyrus (MFG), and amygdala. We found that AV is positively and ANX negatively correlated with task-associated neural activity in the right amygdala, MFG, midcingulate cortex, and superior parietal lobule, and in bilateral IFG. These data suggest that avoidantly attached adults activate brain areas implicated in emotion regulation and cognitive control to a larger extent than anxiously attached individuals during mentalizing. PMID:26162239

  20. Estimation of Locomotion States of a Rat by Neural Signals from the Motor Cortices Based on a Linear Correlation Model

    NASA Astrophysics Data System (ADS)

    Fukayama, Osamu; Taniguchi, Noriyuki; Suzuki, Takafumi; Mabuchi, Kunihiko

    We are developing a brain-machine interface (BMI) called “RatCar," a small vehicle controlled by the neural signals of a rat's brain. An unconfined adult rat with a set of bundled neural electrodes in the brain rides on the vehicle. Each bundle consists of four tungsten wires isolated with parylene polymer. These bundles were implanted in the primary motor and premotor cortices in both hemispheres of the brain. In this paper, methods and results for estimating locomotion speed and directional changes are described. Neural signals were recorded as the rat moved in a straight line and as it changed direction in a curve. Spike-like waveforms were then detected and classified into several clusters to calculate a firing rate for each neuron. The actual locomotion velocity and directional changes of the rat were recorded concurrently. Finally, the locomotion states were correlated with the neural firing rates using a simple linear model. As a result, the abstract estimation of the locomotion velocity and directional changes were achieved.

  1. A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry

    PubMed Central

    Ikeda, Keiko; Takahashi, Masanori; Sato, Shigeru; Igarashi, Hiroyuki; Ishizuka, Toru; Yawo, Hiromu; Arata, Satoru; Southard-Smith, E. Michelle; Kawakami, Kiyoshi; Onimaru, Hiroshi

    2015-01-01

    The key role of the respiratory neural center is respiratory rhythm generation to maintain homeostasis through the control of arterial blood pCO2/pH and pO2 levels. The neuronal network responsible for respiratory rhythm generation in neonatal rat resides in the ventral side of the medulla and is composed of two groups; the parafacial respiratory group (pFRG) and the pre-Bötzinger complex group (preBötC). The pFRG partially overlaps in the retrotrapezoid nucleus (RTN), which was originally identified in adult cats and rats. Part of the pre-inspiratory (Pre-I) neurons in the RTN/pFRG serves as central chemoreceptor neurons and the CO2 sensitive Pre-I neurons express homeobox gene Phox2b. Phox2b encodes a transcription factor and is essential for the development of the sensory-motor visceral circuits. Mutations in human PHOX2B cause congenital hypoventilation syndrome, which is characterized by blunted ventilatory response to hypercapnia. Here we describe the generation of a novel transgenic (Tg) rat harboring fluorescently labeled Pre-I neurons in the RTN/pFRG. In addition, the Tg rat showed fluorescent signals in autonomic enteric neurons and carotid bodies. Because the Tg rat expresses inducible Cre recombinase in PHOX2B-positive cells during development, it is a potentially powerful tool for dissecting the entire picture of the respiratory neural network during development and for identifying the CO2/O2 sensor molecules in the adult central and peripheral nervous systems. PMID:26147470

  2. Live Imaging of Adult Neural Stem Cells in Rodents

    PubMed Central

    Ortega, Felipe; Costa, Marcos R.

    2016-01-01

    The generation of cells of the neural lineage within the brain is not restricted to early development. New neurons, oligodendrocytes, and astrocytes are produced in the adult brain throughout the entire murine life. However, despite the extensive research performed in the field of adult neurogenesis during the past years, fundamental questions regarding the cell biology of adult neural stem cells (aNSCs) remain to be uncovered. For instance, it is crucial to elucidate whether a single aNSC is capable of differentiating into all three different macroglial cell types in vivo or these distinct progenies constitute entirely separate lineages. Similarly, the cell cycle length, the time and mode of division (symmetric vs. asymmetric) that these cells undergo within their lineage progression are interesting questions under current investigation. In this sense, live imaging constitutes a valuable ally in the search of reliable answers to the previous questions. In spite of the current limitations of technology new approaches are being developed and outstanding amount of knowledge is being piled up providing interesting insights in the behavior of aNSCs. Here, we will review the state of the art of live imaging as well as the alternative models that currently offer new answers to critical questions. PMID:27013941

  3. Axonal Control of the Adult Neural Stem Cell Niche

    PubMed Central

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  4. Axonal control of the adult neural stem cell niche.

    PubMed

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D; Tecott, Laurence H; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-04-01

    The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain's neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  5. Neural depolarization triggers Mg2+ influx in rat hippocampal neurons.

    PubMed

    Yamanaka, R; Shindo, Y; Karube, T; Hotta, K; Suzuki, K; Oka, K

    2015-12-01

    Homeostasis of magnesium ion (Mg(2+)) plays key roles in healthy neuronal functions, and deficiency of Mg(2+) is involved in various neuronal diseases. In neurons, we have reported that excitotoxicity induced by excitatory neurotransmitter glutamate increases intracellular Mg(2+) concentration ([Mg(2+)]i). However, it has not been revealed whether neuronal activity under physiological condition modulates [Mg(2+)]i. The aim of this study is to explore the direct relationship between neural activity and [Mg(2+)]i dynamics. In rat primary-dissociated hippocampal neurons, the [Mg(2+)]i and [Ca(2+)]i dynamics were simultaneously visualized with a highly selective fluorescent Mg(2+) probe, KMG-104, and a fluorescent Ca(2+) probe, Fura Red, respectively. [Mg(2+)]i increase concomitant with neural activity by direct current stimulation was observed in neurons plated on an indium-tin oxide (ITO) glass electrode, which enables fluorescent imaging during neural stimulation. The neural activity-dependent [Mg(2+)]i increase was also detected in neurons whose excitability was enhanced by the treatment of a voltage-gated K(+) channel blocker, tetraethylammonium (TEA) at the timings of spontaneous Ca(2+) increase. Furthermore, the [Mg(2+)]i increase was abolished in Mg(2+)-free extracellular medium, indicating [Mg(2+)]i increase is due to Mg(2+) influx induced by neural activity. The direct neuronal depolarization by veratridine, a Na(+) channel opener, induced [Mg(2+)]i increase, and this [Mg(2+)]i increase was suppressed by the pretreatment of a non-specific Mg(2+) channel inhibitor, 2-aminoethoxydiphenyl borate (2-APB). Overall, activity-dependent [Mg(2+)]i increase results from Mg(2+) influx through 2-APB-sensitive channels in rat hippocampal neurons. PMID:26455951

  6. Intraoperative Neural Response Telemetry and Neural Recovery Function: a Comparative Study between Adults and Children

    PubMed Central

    Carvalho, Bettina; Hamerschmidt, Rogerio; Wiemes, Gislaine

    2014-01-01

    Introduction Neural response telemetry (NRT) is a method of capturing the action potential of the distal portion of the auditory nerve in cochlear implant (CI) users, using the CI itself to elicit and record the answers. In addition, it can also measure the recovery function of the auditory nerve (REC), that is, the refractory properties of the nerve. It is not clear in the literature whether the responses from adults are the same as those from children. Objective To compare the results of NRT and REC between adults and children undergoing CI surgery. Methods Cross-sectional, descriptive, and retrospective study of the results of NRT and REC for patients undergoing IC at our service. The NRT is assessed by the level of amplitude (microvolts) and REC as a function of three parameters: A (saturation level, in microvolts), t0 (absolute refractory period, in seconds), and tau (curve of the model function), measured in three electrodes (apical, medial, and basal). Results Fifty-two patients were evaluated with intraoperative NRT (26 adults and 26 children), and 24 with REC (12 adults and 12 children). No statistically significant difference was found between intraoperative responses of adults and children for NRT or for REC's three parameters, except for parameter A of the basal electrode. Conclusion The results of intraoperative NRT and REC were not different between adults and children, except for parameter A of the basal electrode. PMID:25992145

  7. Neural circuitry for rat recognition memory

    PubMed Central

    Warburton, E.C.; Brown, M.W.

    2015-01-01

    Information concerning the roles of different brain regions in recognition memory processes is reviewed. The review concentrates on findings from spontaneous recognition memory tasks performed by rats, including memory for single objects, locations, object–location associations and temporal order. Particular emphasis is given to the potential roles of different regions in the circuit of interacting structures involving the perirhinal cortex, hippocampus, medial prefrontal cortex and medial dorsal thalamus in recognition memory for the association of objects and places. It is concluded that while all structures in this circuit play roles critical to such memory, these roles can potentially be differentiated and differences in the underlying synaptic and biochemical processes involved in each region are beginning to be uncovered. PMID:25315129

  8. Isolation, culture and analysis of adult subependymal neural stem cells.

    PubMed

    Belenguer, Germán; Domingo-Muelas, Ana; Ferrón, Sacri R; Morante-Redolat, José Manuel; Fariñas, Isabel

    2016-01-01

    Individual cells dissected from the subependymal neurogenic niche of the adult mouse brain proliferate in medium containing basic fibroblast growth factor (bFGF) and/or epidermal growth factor (EGF) as mitogens, to produce multipotent clonal aggregates called neurospheres. These cultures constitute a powerful tool for the study of neural stem cells (NSCs) provided that they allow the analysis of their features and potential capacity in a controlled environment that can be modulated and monitored more accurately than in vivo. Clonogenic and population analyses under mitogen addition or withdrawal allow the quantification of the self-renewing and multilineage potency of these cells and the identification of the mechanisms involved in these properties. Here, we describe a set of procedures developed and/or modified by our group including several experimental options that can be used either independently or in combination for the ex vivo assessment of cell properties of NSCs obtained from the adult subependymal niche. PMID:27016251

  9. Magnetic resonance tracking of nanoparticle labelled neural stem cells in a rat's spinal cord

    NASA Astrophysics Data System (ADS)

    Wang, F. H.; Lee, I. H.; Holmström, N.; Yoshitake, T.; Kim, D. K.; Muhammed, M.; Frisén, J.; Olson, L.; Spenger, C.; Kehr, J.

    2006-04-01

    Neural stem cells isolated from an adult rat's spinal cord were loaded with superparamagnetic gold-coated monocrystalline iron oxide nanoparticles (Au-MION) intended for use as contrast enhancers in magnetic resonance imaging (MRI). A dose-dependent attenuation of MRI signals was observed for Au-MION down to 0.001 µg Fe/µl and for nanoparticle-loaded clusters of only 20 cells. The labelled cells were infused into the spinal cord of anaesthetized rats and tracked by MRI at 1 h, 48 h and 1 month post-injection. Histological analysis revealed that MRI signals correlated well with gold-positive staining of transplanted cells. The present results show that Au-MION exerts powerful contrast-enhancing properties and may represent novel MRI labels for labelling and tracking the transplanted cells in vivo.

  10. Neural Processing of Emotional Prosody across the Adult Lifespan

    PubMed Central

    Demenescu, Liliana Ramona; Kato, Yutaka; Mathiak, Klaus

    2015-01-01

    Emotion recognition deficits emerge with the increasing age, in particular, a decline in the identification of sadness. However, little is known about the age-related changes of emotion processing in sensory, affective, and executive brain areas. This functional magnetic resonance imaging (fMRI) study investigated neural correlates of auditory processing of prosody across adult lifespan. Unattended detection of emotional prosody changes was assessed in 21 young (age range: 18–35 years), 19 middle-aged (age range: 36–55 years), and 15 older (age range: 56–75 years) adults. Pseudowords uttered with neutral prosody were standards in an oddball paradigm with angry, sad, happy, and gender deviants (total 20% deviants). Changes in emotional prosody and voice gender elicited bilateral superior temporal gyri (STG) responses reflecting automatic encoding of prosody. At the right STG, responses to sad deviants decreased linearly with age, whereas happy events exhibited a nonlinear relationship. In contrast to behavioral data, no age by sex interaction emerged on the neural networks. The aging decline of emotion processing of prosodic cues emerges already at an early automatic stage of information processing at the level of the auditory cortex. However, top-down modulation may lead to an additional perceptional bias, for example, towards positive stimuli, and may depend on context factors such as the listener's sex. PMID:26583118

  11. Neural Processing of Emotional Prosody across the Adult Lifespan.

    PubMed

    Demenescu, Liliana Ramona; Kato, Yutaka; Mathiak, Klaus

    2015-01-01

    Emotion recognition deficits emerge with the increasing age, in particular, a decline in the identification of sadness. However, little is known about the age-related changes of emotion processing in sensory, affective, and executive brain areas. This functional magnetic resonance imaging (fMRI) study investigated neural correlates of auditory processing of prosody across adult lifespan. Unattended detection of emotional prosody changes was assessed in 21 young (age range: 18-35 years), 19 middle-aged (age range: 36-55 years), and 15 older (age range: 56-75 years) adults. Pseudowords uttered with neutral prosody were standards in an oddball paradigm with angry, sad, happy, and gender deviants (total 20% deviants). Changes in emotional prosody and voice gender elicited bilateral superior temporal gyri (STG) responses reflecting automatic encoding of prosody. At the right STG, responses to sad deviants decreased linearly with age, whereas happy events exhibited a nonlinear relationship. In contrast to behavioral data, no age by sex interaction emerged on the neural networks. The aging decline of emotion processing of prosodic cues emerges already at an early automatic stage of information processing at the level of the auditory cortex. However, top-down modulation may lead to an additional perceptional bias, for example, towards positive stimuli, and may depend on context factors such as the listener's sex. PMID:26583118

  12. Hydrogen sulfide improves neural function in rats following cardiopulmonary resuscitation

    PubMed Central

    LIN, JI-YAN; ZHANG, MIN-WEI; WANG, JIN-GAO; LI, HUI; WEI, HONG-YAN; LIU, RONG; DAI, GANG; LIAO, XIAO-XING

    2016-01-01

    The alleviation of brain injury is a key issue following cardiopulmonary resuscitation (CPR). Hydrogen sulfide (H2S) is hypothesized to be involved in the pathophysiological process of ischemia-reperfusion injury, and exerts a protective effect on neurons. The aim of the present study was to investigate the effects of H2S on neural functions following cardiac arrest (CA) in rats. A total of 60 rats were allocated at random into three groups. CA was induced to establish the model and CPR was performed after 6 min. Subsequently, sodium hydrosulfide (NaHS), hydroxylamine or saline was administered to the rats. Serum levels of H2S, neuron-specific enolase (NSE) and S100β were determined following CPR. In addition, neurological deficit scoring (NDS), the beam walking test (BWT), prehensile traction test and Morris water maze experiment were conducted. Neuronal apoptosis rates were detected in the hippocampal region following sacrifice. After CPR, as the H2S levels increased or decreased, the serum NSE and S100β concentrations decreased or increased, respectively (P<0.0w. The NDS results of the NaHS group were improved compared with those of the hydroxylamine group at 24 h after CPR (P<0.05). In the Morris water maze experiment, BWT and prehensile traction test the animals in the NaHS group performed best and rats in the hydroxylamine group performed worst. At day 7, the apoptotic index and the expression of caspase-3 were reduced in the hippocampal CA1 region, while the expression of Bcl-2 increased in the NaHS group; and results of the hydroxylamine group were in contrast. Therefore, the results of the present study indicate that H2S is able to improve neural function in rats following CPR. PMID:26893650

  13. Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling

    SciTech Connect

    Das, Ani V.; Zhao Xing; James, Jackson; Kim, Min; Cowan, Kenneth H.; Ahmad, Iqbal . E-mail: iahmad@unmc.edu

    2006-01-13

    The identification of neural stem cells with retinal potential in the ciliary epithelium (CE) of the adult mammals is of considerable interest because of their potential for replacing or rescuing degenerating retinal neurons in disease or injury. The evaluation of such a potential requires characterization of these cells with regard to their phenotypic properties, potential, and regulatory mechanisms. Here, we demonstrate that rat CE stem cells/progenitors in neurosphere culture display astrocytic nature in terms of expressing glial intermediate neurofilament protein, GFAP. The GFAP-expressing CE stem cells/progenitors form neurospheres in proliferating conditions and generate neurons when shifted to differentiating conditions. These cells express components of the canonical Wnt pathway and its activation promotes their proliferation. Furthermore, we demonstrate that the activation of the canonical Wnt pathway influences neuronal differentiation of CE stem cells/progenitors in a context dependent manner. Our observations suggest that CE stem cells/progenitors share phenotypic properties and regulatory mechanism(s) with neural stem cells elsewhere in the adult CNS.

  14. Endogenous neural precursors influence grafted neural stem cells and contribute to neuroprotection in the Parkinsonian rat

    PubMed Central

    Madhavan, Lalitha; Daley, Brian F; Sortwell, Caryl E; Collier, Timothy J

    2012-01-01

    Neuroprotective and neurorescue effects after neural stem/precursor cell (NPC) transplantation have been reported, but the mechanisms underlying such phenomena are not well understood. Our recent findings in a rat Parkinson’s disease (PD) model indicate that transplantation of NPCs before a 6-hydroxydopamine (6-OHDA) insult can result in nigrostriatal protection which is associated with endogenous NPC proliferation, migration and neurogenesis. Here, we sought to determine whether the observed endogenous NPC response (1) contributes to transplanted NPC - mediated neuroprotection and/or (2) affects graft phenotype and function. Host Fischer 344 rats were administered the antimitotic agent cytosine-β-D-arabinofuranoside (Ara-C) to eliminate actively proliferating endogenous neural precursors before being transplanted with NPCs and treated with 6-OHDA to induce nigrostriatal degeneration. Behavioral and histological analyses demonstrate that the neuroprotective response observed in NPC transplanted animals which had not received Ara-C was significantly attenuated in animals which did receive pre-transplant Ara-C. Also, while grafts in Ara-C treated animals showed no decrease in cell number, they exhibited significantly reduced expression of the neural stem cell regulators nestin and sonic hedgehog. In addition, inhibition of the endogenous NPC response resulted in an exaggerated host glial reaction. Overall, the study establishes for the first time that endogenous NPCs contribute to transplanted NPC-mediated therapeutic effects by affecting both grafted and mature host cells in unique ways. Thus, both endogenous and transplanted NPCs are important in creating an environment suitable for neural protection and rescue, and harnessing their synergistic interaction may lead to the optimization of cell-based therapies for PD. PMID:22417168

  15. Social stress, autonomic neural activation, and cardiac activity in rats.

    PubMed

    Sgoifo, A; Koolhaas, J; De Boer, S; Musso, E; Stilli, D; Buwalda, B; Meerlo, P

    1999-11-01

    Animal models of social stress represent a useful experimental tool to investigate the relationship between psychological stress, autonomic neural activity and cardiovascular disease. This paper summarizes the results obtained in a series of experiments performed on rats and aimed at verifying whether social challenges produce specific modifications in the autonomic neural control of heart rate and whether these changes can be detrimental for cardiac electrical stability. Short-term electrocardiographic recordings were performed via radiotelemetry and the autonomic input to the heart evaluated by means of time-domain heart rate variability measures. Compared to other stress contexts, a social defeat experience produces a strong shift of autonomic balance toward sympathetic dominance, poorly antagonized by vagal rebound, and associated with the occurrence of cardiac tachyarrhythmias. These effects were particularly severe when a wild-type strain of rats was studied. The data also suggest that the cardiac autonomic responses produced by different types of social contexts (dominant-subordinate interaction, dominant-dominant confrontation, social defeat) are related to different degrees of emotional activation, which in turn are likely modulated by the social rank of the experimental animal and the opponent, the prior experience with the stressor, and the level of controllability over the stimulus. PMID:10580306

  16. Auditory Training: Evidence for Neural Plasticity in Older Adults

    PubMed Central

    Anderson, Samira; Kraus, Nina

    2014-01-01

    Improvements in digital amplification, cochlear implants, and other innovations have extended the potential for improving hearing function; yet, there remains a need for further hearing improvement in challenging listening situations, such as when trying to understand speech in noise or when listening to music. Here, we review evidence from animal and human models of plasticity in the brain’s ability to process speech and other meaningful stimuli. We considered studies targeting populations of younger through older adults, emphasizing studies that have employed randomized controlled designs and have made connections between neural and behavioral changes. Overall results indicate that the brain remains malleable through older adulthood, provided that treatment algorithms have been modified to allow for changes in learning with age. Improvements in speech-in-noise perception and cognition function accompany neural changes in auditory processing. The training-related improvements noted across studies support the need to consider auditory training strategies in the management of individuals who express concerns about hearing in difficult listening situations. Given evidence from studies engaging the brain’s reward centers, future research should consider how these centers can be naturally activated during training. PMID:25485037

  17. Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

    PubMed Central

    Hamilton, Derek A.; Magcalas, Christy M.; Barto, Daniel; Bird, Clark W.; Rodriguez, Carlos I.; Fink, Brandi C.; Pellis, Sergio M.; Davies, Suzy; Savage, Daniel D.

    2014-01-01

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE1, and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring. PMID:25549080

  18. Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

    PubMed

    Hamilton, Derek A; Magcalas, Christy M; Barto, Daniel; Bird, Clark W; Rodriguez, Carlos I; Fink, Brandi C; Pellis, Sergio M; Davies, Suzy; Savage, Daniel D

    2014-01-01

    Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring. PMID:25549080

  19. Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population

    PubMed Central

    Giachino, Claudio; Basak, Onur; Lugert, Sebastian; Knuckles, Philip; Obernier, Kirsten; Fiorelli, Roberto; Frank, Stephan; Raineteau, Olivier; Alvarez–Buylla, Arturo; Taylor, Verdon

    2014-01-01

    Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V-SVZ) of rodents produce neurons throughout life while those in humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal and the generation of neurons. Using genetic markers and lineage tracing, we identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a striking heterogeneity including activated, brain lipid binding protein (BLBP, FABP7) expressing stem cells. BLBP+ NSCs are mitotically active components of pinwheel structures in the lateral ventricle walls and persistently generate neurons in adulthood. BLBP+ NSCs express epidermal growth factor (EGF) receptor, proliferate in response to EGF, and are a major clonogenic population in the SVZ. We also find BLBP expressed by proliferative ventricular and sub-ventricular progenitors in the fetal and postnatal human brain. Loss of BLBP+ stem/progenitor cells correlates with reduced neurogenesis in aging rodents and postnatal humans. These findings of molecular heterogeneity and proliferative differences subdivide the NSC population and have implications for neurogenesis in the forebrain of mammals during aging. PMID:23964022

  20. TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation.

    PubMed

    Hillje, A-L; Pavlou, M A S; Beckmann, E; Worlitzer, M M A; Bahnassawy, L; Lewejohann, L; Palm, T; Schwamborn, J C

    2013-01-01

    In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells. In the absence of TRIM32, neuroblasts differentiate slower and show gene expression profiles that are characteristic of immature cells. Interestingly, TRIM32 deficiency induces more neural progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated olfactory bulb neurons of TRIM32 knockout mice. These results highlight the function of the cell fate-determinant TRIM32 for a balanced activity of the adult neurogenesis process. PMID:24357807

  1. Neurite formation by neurons derived from adult rat hippocampal progenitor cells is susceptible to myelin inhibition.

    PubMed

    Mellough, Carla B; Cho, Seongeun; Wood, Andrew; Przyborski, Stefan

    2011-09-01

    Myelin-associated inhibitors expressed following injury to the adult central nervous system (CNS) induce growth cone collapse and retraction of the axonal cytoskeleton. Myelin-associated glycoprotein (MAG) is a bi-functional molecule that promotes neuritogenesis in some immature neurons during development then becomes inhibitory to neurite outgrowth as neurons mature. Progress is being made towards the elucidation of the downstream events that regulate myelin inhibition of regeneration in neuronal populations. However it is not known how adult-derived neural stem cells or progenitors respond to myelin during neuronal differentiation and neuritogenesis. Here we examine the effect of MAG on neurons derived from an adult rat hippocampal progenitor cell line (AHPCs). We show that, unlike their developmental counterparts, AHPC-derived neurons are susceptible to MAG inhibition of neuritogenesis during differentiation and display a 57% reduction in neurite outgrowth when compared with controls. We demonstrate that this effect can be overcome (by up to 69%) by activation of the neurotrophin, cyclic AMP and protein kinase A pathways or by Rho-kinase suppression. We also demonstrate that combination of these factors enhanced neurite outgrowth from differentiating neurons in the presence of MAG. This work provides important information for the successful generation of new neurons from adult neural stem cell populations within compromised adult circuitry and is thus directly relevant to endogenous repair and regeneration of the adult CNS. PMID:21256909

  2. ACUTE BEHAVIORAL TOXICITY OF CARBARYL AND PROPOXUR IN ADULT RATS

    EPA Science Inventory

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8,...

  3. Neural correlates of executive attention in adults born very preterm

    PubMed Central

    Daamen, Marcel; Bäuml, Josef G.; Scheef, Lukas; Meng, Chun; Jurcoane, Alina; Jaekel, Julia; Sorg, Christian; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra; Boecker, Henning

    2015-01-01

    Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing. PMID:26640769

  4. Neural correlates of executive attention in adults born very preterm.

    PubMed

    Daamen, Marcel; Bäuml, Josef G; Scheef, Lukas; Meng, Chun; Jurcoane, Alina; Jaekel, Julia; Sorg, Christian; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra; Boecker, Henning

    2015-01-01

    Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing. PMID:26640769

  5. Zhichan decoction induces differentiation of dopaminergic neurons in Parkinson's disease rats after neural stem cell transplantation

    PubMed Central

    Shi, Huifen; Song, Jie; Yang, Xuming

    2014-01-01

    The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson's disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite (dihydroxyphenylacetic acid and homovanillic acid) content in the midbrain of Parkinson's disease rats was increased after neural stem cell transplantation + Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation + Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson's disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons. PMID:25206914

  6. TRIMETHYLTIN DISRUPTS ACOUSTIC STARTLE RESPONDING IN ADULT RATS

    EPA Science Inventory

    Trimethyltin (TMT) is a limbic-system toxicant which also produces sensory dysfunction in adult animals. In the present experiment, the authors examined the effects of TMT on the acoustic startle response. Adult male, Long-Evans rats (N=12/dose) received a single i.p. injection o...

  7. Roles of neural stem cells and adult neurogenesis in adolescent alcohol use disorders

    PubMed Central

    Nixon, K.; Morris, S.A.; Liput, D.J.; Kelso, M.L.

    2009-01-01

    This review discusses the contributions of a newly considered form of plasticity, the ongoing production of new neurons from neural stem cells, or adult neurogenesis, within the context of neuropathologies that occur with excessive alcohol intake in the adolescent. Neural stem cells and adult neurogenesis are now thought to contribute to the structural integrity of the hippocampus, a limbic system region involved in learning, memory, behavioral control, and mood. In adolescents with alcohol use disorders, the hippocampus appears to be particularly vulnerable to the neurodegenerative effects of alcohol, but the role of neural stem cells and adult neurogenesis in alcoholic neuropathology has only recently been considered. This review encompasses a brief overview of neural stem cells and the processes involved in adult neurogenesis, how neural stem cells are affected by alcohol, and possible differences in the neurogenic niche between adults and adolescents. Specifically, what is known about developmental differences in adult neurogenesis between the adult and adolescent is gleaned from the literature, as well as how alcohol affects this process differently between the age groups. And finally, this review suggests differences that may exist in the neurogenic niche between adults and adolescents and how these differences may contribute to the susceptibility of the adolescent hippocampus to damage. However, many more studies are needed to discern whether these developmental differences contribute to the vulnerability of the adolescent to developing an alcohol use disorder. PMID:20113873

  8. Neural control of glutamine synthetase activity in rat skeletal muscles.

    PubMed

    Feng, B; Konagaya, M; Konagaya, Y; Thomas, J W; Banner, C; Mill, J; Max, S R

    1990-05-01

    The mechanism of glutamine synthetase induction in rat skeletal muscle after denervation or limb immobilization was investigated. Adult male rats were subjected to midthigh section of the sciatic nerve. At 1, 2, and 5 h and 1, 2, and 7 days after denervation, rats were killed and denervated, and contralateral control soleus and plantaris muscles were excised, weighted, homogenized, and assayed for glutamine synthetase. Glutamine synthetase activity increased approximately twofold 1 h after denervation in both muscles. By 7 days postdenervation enzyme activity had increased to three times the control level in plantaris muscle and to four times the control level in soleus muscle. Increased enzyme activity after nerve section was associated with increased maximum velocity with no change in apparent Michaelis constant. Immunotitration with an antiglutamine synthetase antibody suggested that denervation caused an increase in the number of glutamine synthetase molecules in muscle. However, Northern-blot analysis revealed no increase in the steady-state level of glutamine synthetase mRNA after denervation. A mixing experiment failed to yield evidence for the presence of a soluble factor involved in regulating the activity of glutamine synthetase in denervated muscle. A combination of denervation and dexamethasone injections resulted in additive increases in glutamine synthetase. Thus the mechanism underlying increased glutamine synthetase after denervation appears to be posttranscriptional and is distinct from that of the glucocorticoid-mediated glutamine synthetase induction previously described by us. PMID:1970709

  9. A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis123

    PubMed Central

    Grigereit, Laura; Pickel, James

    2016-01-01

    Abstract The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis. PMID:27257630

  10. Differences in Feedback- and Inhibition-Related Neural Activity in Adult ADHD

    ERIC Educational Resources Information Center

    Dibbets, Pauline; Evers, Lisbeth; Hurks, Petra; Marchetta, Natalie; Jolles, Jelle

    2009-01-01

    The objective of this study was to examine response inhibition- and feedback-related neural activity in adults with attention deficit hyperactivity disorder (ADHD) using event-related functional MRI. Sixteen male adults with ADHD and 13 healthy/normal controls participated in this study and performed a modified Go/NoGo task. Behaviourally,…

  11. Chondroitin sulphate-mediated fusion of brain neural folds in rat embryos.

    PubMed

    Alonso, M I; Moro, J A; Martín, C; de la Mano, A; Carnicero, E; Martínez-Alvarez, C; Navarro, N; Cordero, J; Gato, A

    2009-01-01

    Previous studies have demonstrated that during neural fold fusion in different species, an apical extracellular material rich in glycoconjugates is involved. However, the composition and the biological role of this material remain undetermined. In this paper, we show that this extracellular matrix in rat increases notably prior to contact between the neural folds, suggesting the dynamic behaviour of the secretory process. Immunostaining has allowed us to demonstrate that this extracellular matrix contains chondroitin sulphate proteoglycan (CSPG), with a spatio-temporal distribution pattern, suggesting a direct relationship with the process of adhesion. The degree of CSPG involvement in cephalic neural fold fusion in rat embryos was determined by treatment with specific glycosidases.In vitro rat embryo culture and microinjection techniques were employed to carry out selective digestion, with chondroitinase AC, of the CSPG on the apical surface of the neural folds; this was done immediately prior to the bonding of the cephalic neural folds. In all the treated embryos, cephalic defects of neural fold fusion could be detected. These results show that CSPG plays an important role in the fusion of the cephalic neural folds in rat embryos, which implies that this proteoglycan could be involved in cellular recognition and adhesion. PMID:18836253

  12. Migration and Differentiation of Neural Progenitor Cells after Recurrent Laryngeal Nerve Avulsion in Rats

    PubMed Central

    Zhao, Wan; Xu, Wen

    2014-01-01

    To investigate migration and differentiation of neural progenitor cells (NPCs) from the ependymal layer to the nucleus ambiguus (NA) after recurrent laryngeal nerve (RLN) avulsion. All of the animals received a CM-DiI injection in the left lateral ventricle. Forty-five adult rats were subjected to a left RLN avulsion injury, and nine rats were used as controls. 5-Bromo-2-deoxyuridine (BrdU) was injected intraperitoneally. Immunohistochemical analyses were performed in the brain stems at different time points after RLN injury. After RLN avulsion, the CM-DiI+ NPCs from the ependymal layer migrated to the lesioned NA. CM-DiI+/GFAP+ astrocytes, CM-DiI+/DCX+ neuroblasts and CM-DiI+/NeuN+ neurons were observed in the migratory stream. However, the ipsilateral NA included only CM-DiI+ astrocytes, not newborn neurons. After RLN avulsion, the NPCs in the ependymal layer of the 4th ventricle or central canal attempt to restore the damaged NA. We first confirm that the migratory stream includes both neurons and glia differentiated from the NPCs. However, only differentiated astrocytes are successfully incorporated into the NA. The presence of both cell types in the migratory process may play a role in repairing RLN injuries. PMID:25202908

  13. Behavioral effects of corpus callosum transection and environmental enrichment in adult rats.

    PubMed

    Miu, Andrei C; Heilman, Renata M; Paşca, Sergiu P; Stefan, Catrinel A; Spânu, Florina; Vasiu, Renata; Olteanu, Adrian I; Miclea, Mircea

    2006-09-15

    A common assumption about the corpus callosum transection (CCX) is that it only affects behaviors heavily relying on interhemispheric communication. However, cerebral laterality is ubiquitous across motor and perceptual, cognitive and emotional domains, and the corpus callosum is important for its establishment. Several recent studies showed that the partial denervation of the sensorimotor isocortex through CCX derepressed neural growth processes that were sensitive to motor demand (experience-dependent neural plasticity). We investigated whether the facilitatory effects of CCX on cortical neural plasticity, shaped by differential housing, extended beyond the motor domain. Adult rats were housed in enriched (EE), standard (SE) or impoverished environments (IE) for 10 weeks, that is, 2 weeks before they underwent CCX or sham surgery, and, then, 8 weeks throughout the experiments. After they recovered from surgery, the behavioral performance of rats was tested using open-field, spontaneous alternation in the T-maze, paw preference, Morris water maze, and tone fear conditioning. The results indicated that the effects of CCX and housing on open-field behavior were independent, with CCX increasing the time spent in the center of the field at the beginning of the observation (i.e., emotionality), and EE and IE increasing rearing (emotionality) and reducing teeth-chattering (habituation), respectively. CCX reduced the frequency of spontaneous alternation, denoting spatial working memory deficits, while housing did not influence this performance. Neither CCX, nor housing significantly affected paw preference lateralization, although CCX was associated with a leftward bias in paw preference. In the Morris water maze, housing had effects on spatial acquisition, while CCX reduced activity, without interfering with spatial memory. CCX did not influence tone fear conditioning, but context fear conditioning seemed to benefit from EE. We conclude that CCX in adult rats has subtle

  14. Behavioral and Neural Discrimination of Speech Sounds After Moderate or Intense Noise Exposure in Rats

    PubMed Central

    Reed, Amanda C.; Centanni, Tracy M.; Borland, Michael S.; Matney, Chanel J.; Engineer, Crystal T.; Kilgard, Michael P.

    2015-01-01

    Objectives Hearing loss is a commonly experienced disability in a variety of populations including veterans and the elderly and can often cause significant impairment in the ability to understand spoken language. In this study, we tested the hypothesis that neural and behavioral responses to speech will be differentially impaired in an animal model after two forms of hearing loss. Design Sixteen female Sprague–Dawley rats were exposed to one of two types of broadband noise which was either moderate or intense. In nine of these rats, auditory cortex recordings were taken 4 weeks after noise exposure (NE). The other seven were pretrained on a speech sound discrimination task prior to NE and were then tested on the same task after hearing loss. Results Following intense NE, rats had few neural responses to speech stimuli. These rats were able to detect speech sounds but were no longer able to discriminate between speech sounds. Following moderate NE, rats had reorganized cortical maps and altered neural responses to speech stimuli but were still able to accurately discriminate between similar speech sounds during behavioral testing. Conclusions These results suggest that rats are able to adjust to the neural changes after moderate NE and discriminate speech sounds, but they are not able to recover behavioral abilities after intense NE. Animal models could help clarify the adaptive and pathological neural changes that contribute to speech processing in hearing-impaired populations and could be used to test potential behavioral and pharmacological therapies. PMID:25072238

  15. Physiological responses during whole body suspension of adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Fell, R. D.; Musacchia, X. J.

    1987-01-01

    The objective of this study was to characterize responses of adult rats to one and two weeks of whole body suspension. Body weights and food and water intakes were initially reduced during suspension, but, while intake of food and water returned to presuspension levels, body weight remained depressed. Diuresis was evident, but only during week two. Hindlimb muscle responses were differential, with the soleus exhibiting the greatest atrophy and the EDL a relative hypertrophy. These findings suggest that adult rats respond qualitatively in a manner similar to juveniles during suspension.

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

    PubMed Central

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

    2012-01-01

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

  17. Changes in metabolic proteins in ex vivo rat retina during glutamate-induced neural progenitor cell induction.

    PubMed

    Tokuda, Kazuhiro; Kuramitsu, Yasuhiro; Baron, Byron; Kitagawa, Takao; Tokuda, Nobuko; Kobayashi, Masaaki; Kimura, Kazuhiro; Sonoda, Koh-Hei; Nakamura, Kazuyuki

    2016-08-01

    Understanding how energy metabolism and related proteins influence neural progenitor cells in adult tissues is critical for developing new strategies in clinical tissue regeneration therapy. We have recently reported that a subtoxic concentration of glutamate-induced neural progenitor cells in the mature ex vivo rat retina. We herein explore changes in the metabolic pathways during the process. We firstly observed an increase in lactate and lactate dehydrogenase concentration in the glutamate-treated retina. We then investigated the levels of glycolytic enzymes and confirmed significant upregulation of pyruvate kinase M type (PKM), especially PKM2, enolase, phosphoglycerate mutase 1 (PGAM1), and inosine-5'-monophosphate dehydrogenase (IMPDH1) in the glutamate-treated retina compared to the untreated retina. An analysis of the subcellular localization of PKM2 revealed nuclear translocation in the treated retina, which has been reported to regulate cell cycle proliferation and glycolytic enzymes. Our findings indicate that the mature rat retina undergoes an increase in aerobic glycolysis. PKM2, both in the cytoplasm and in the nucleus, may thus play an important role during neural progenitor cell induction, as it does in other proliferating cells. PMID:27421851

  18. Gypenosides Protected the Neural Stem Cells in the Subventricular Zone of Neonatal Rats that Were Prenatally Exposed to Ethanol

    PubMed Central

    Dong, Lun; Yang, Kun-Qi; Fu, Wen-Yan; Shang, Zhen-Hua; Zhang, Qing-Yu; Jing, Fang-Miao; Li, Lin-Lin; Xin, Hua; Wang, Xiao-Jing

    2014-01-01

    Fetal alcohol spectrum disorder (FASD) can cause severe mental retardation in children who are prenatally exposed to ethanol. The effects of prenatal and early postnatal ethanol exposure on adult hippocampal neurogenesis have been investigated; however, the effects of prenatal ethanol exposure on the subventricular zone (SVZ) have not. Gypenosides (GPs) have been reported to have neuroprotective effects in addition to other bioactivities. The effects of GPs on neural stem cells (NSCs) in the FASD model are unknown. Here, we test the effect of prenatal ethanol exposure on the neonatal SVZ, and the protection potential of GPs on NSCs in FASD rats. Our results show that prenatal ethanol exposure can suppress the cell proliferation and differentiation of neural stem cells in the neonatal SVZ and that GPs (400 mg/kg/day) can significantly increase the cell proliferation and differentiation of neural stem cells inhibited by ethanol. Our data indicate that GPs have neuroprotective effects on the NSCs and can enhance the neurogenesis inhibited by ethanol within the SVZ of neonatal rats. These findings provide new evidence for a potential therapy involving GPs for the treatment of FASD. PMID:25464383

  19. Leptin-dependent neurotoxicity via induction of apoptosis in adult rat neurogenic cells

    PubMed Central

    Segura, Stéphanie; Efthimiadi, Laurie; Porcher, Christophe; Courtes, Sandrine; Coronas, Valérie; Krantic, Slavica; Moyse, Emmanuel

    2015-01-01

    Adipocyte-derived hormone leptin has been recently implicated in the control of neuronal plasticity. To explore whether modulation of adult neurogenesis may contribute to leptin control of neuronal plasticity, we used the neurosphere assay of neural stem cells derived from the adult rat subventricular zone (SVZ). Endogenous expression of specific leptin receptor (ObRb) transcripts, as revealed by RT-PCR, is associated with activation of both ERK and STAT-3 pathways via phosphorylation of the critical ERK/STAT-3 amino acid residues upon addition of leptin to neurospheres. Furthermore, leptin triggered withdrawal of neural stem cells from the cell cycle as monitored by Ki67 labeling. This effect was blocked by pharmacological inhibition of ERK activation thus demonstrating that ERK mediates leptin effects on neural stem cell expansion. Leptin-dependent withdrawal of neural stem cells from the cell cycle was associated with increased apoptosis, as detected by TUNEL, which was preceded by cyclin D1 induction. Cyclin D1 was indeed extensively colocalized with TUNEL-positive, apoptotic nuclei. Cyclin-D1 silencing by specific shRNA prevented leptin-induced decrease of the cell number per neurosphere thus pointing to the causal relationship between leptin actions on apoptosis and cyclin D1 induction. Leptin target cells in SVZ neurospheres were identified by double TUNEL/phenotypic marker immunocytofluorescence as differentiating neurons mostly. The inhibition of neural stem cell expansion via ERK/cyclin D1-triggered apoptosis defines novel biological action of leptin which may be involved in adiposity-dependent neurotoxicity. PMID:26441523

  20. Early life stress induces renal dysfunction in adult male rats but not female rats

    PubMed Central

    Loria, Analia S.; Yamamoto, Tatsuo; Pollock, Jennifer S.

    2013-01-01

    Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats. PMID:23174859

  1. Improved discriminability of spatiotemporal neural patterns in rat motor cortical areas as directional choice learning progresses

    PubMed Central

    Mao, Hongwei; Yuan, Yuan; Si, Jennie

    2015-01-01

    Animals learn to choose a proper action among alternatives to improve their odds of success in food foraging and other activities critical for survival. Through trial-and-error, they learn correct associations between their choices and external stimuli. While a neural network that underlies such learning process has been identified at a high level, it is still unclear how individual neurons and a neural ensemble adapt as learning progresses. In this study, we monitored the activity of single units in the rat medial and lateral agranular (AGm and AGl, respectively) areas as rats learned to make a left or right side lever press in response to a left or right side light cue. We noticed that rat movement parameters during the performance of the directional choice task quickly became stereotyped during the first 2–3 days or sessions. But learning the directional choice problem took weeks to occur. Accompanying rats' behavioral performance adaptation, we observed neural modulation by directional choice in recorded single units. Our analysis shows that ensemble mean firing rates in the cue-on period did not change significantly as learning progressed, and the ensemble mean rate difference between left and right side choices did not show a clear trend of change either. However, the spatiotemporal firing patterns of the neural ensemble exhibited improved discriminability between the two directional choices through learning. These results suggest a spatiotemporal neural coding scheme in a motor cortical neural ensemble that may be responsible for and contributing to learning the directional choice task. PMID:25798093

  2. Functional MRI and neural responses in a rat model of Alzheimer’s disease

    PubMed Central

    Sanganahalli, Basavaraju G.; Herman, Peter; Behar, Kevin L.; Blumenfeld, Hal; Rothman, Douglas L.; Hyder, Fahmeed

    2013-01-01

    Based on the hypothesis that brain plaques and tangles can affect cortical functions in Alzheimer's disease (AD) and thus modify functional activity, we investigated functional responses in an AD rat model (called the Samaritan Alzheimer’s rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer’s disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer’s disease. PMID:23648961

  3. A role for the prefrontal cortex in heroin-seeking after forced abstinence by adult male rats but not adolescents.

    PubMed

    Doherty, James M; Cooke, Bradley M; Frantz, Kyle J

    2013-02-01

    Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration. PMID:23072838

  4. A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents

    PubMed Central

    Doherty, James M; Cooke, Bradley M; Frantz, Kyle J

    2013-01-01

    Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir+ and Fos-ir− neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir+ neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration. PMID:23072838

  5. Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome.

    PubMed

    Engineer, Crystal T; Rahebi, Kimiya C; Borland, Michael S; Buell, Elizabeth P; Centanni, Tracy M; Fink, Melyssa K; Im, Kwok W; Wilson, Linda G; Kilgard, Michael P

    2015-11-01

    Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. PMID:26321676

  6. Neural Correlates Associated with Successful Working Memory Performance in Older Adults as Revealed by Spatial ICA

    PubMed Central

    Saliasi, Emi; Geerligs, Linda; Lorist, Monicque M.; Maurits, Natasha M.

    2014-01-01

    To investigate which neural correlates are associated with successful working memory performance, fMRI was recorded in healthy younger and older adults during performance on an n-back task with varying task demands. To identify functional networks supporting working memory processes, we used independent component analysis (ICA) decomposition of the fMRI data. Compared to younger adults, older adults showed a larger neural (BOLD) response in the more complex (2-back) than in the baseline (0-back) task condition, in the ventral lateral prefrontal cortex (VLPFC) and in the right fronto-parietal network (FPN). Our results indicated that a higher BOLD response in the VLPFC was associated with increased performance accuracy in older adults, in both the baseline and the more complex task condition. This ‘BOLD-performance’ relationship suggests that the neural correlates linked with successful performance in the older adults are not uniquely related to specific working memory processes present in the complex but not in the baseline task condition. Furthermore, the selective presence of this relationship in older but not in younger adults suggests that increased neural activity in the VLPFC serves a compensatory role in the aging brain which benefits task performance in the elderly. PMID:24911016

  7. ACUTE TOXICITY OF PESTICIDES IN ADULT AND WEANLING RATS

    EPA Science Inventory

    LD sub 50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and 4 test...

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

    PubMed

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

    1999-06-01

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

  9. High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells

    PubMed Central

    Kong, Chae-Gwan; Kim, Man Soo; Park, Eun-Young

    2014-01-01

    Study Design In vitro cell culture. Purpose The purpose of this study was to investigate the effect of high glucose on autophagy in adult rat intervertebral disc cells. Overview of Literature Diabetes mellitus is considered to be an important etiologic factor for intervertebral disc degeneration, resulting in degenerative disc diseases. A glucose-mediated increase of autophagy is a major causative factor for the development of diseases associated with diabetes mellitus. However, no information is available for the effect of high glucose on autophagy in adult intervertebral disc cells. Methods Nucleus pulposus and annulus fibrosus cells were isolated from 24-week-old adult rats, cultured and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. The expressions of autophagy markers, such as beclin-1, light chain 3-I (LC3-I) and LC3-II, autophagy-related gene (Atg) 3, 5, 7 and 12, were identified and quantified. Results Two high glucoses significantly increased the expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in adult rat nucleus pulposus and annulus fibrosus cells in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-respectively time-dependent manner. Conclusions The results suggest that autophagy of adult nucleus pulposus and annulus fibrosus cells might be a potential mechanism for the intervertebral disc degeneration in adult patients with diabetes mellitus. Thus, the prevention of autophagy in adult intervertebral disc cells might be considered as a novel therapeutic target to prevent or to delay the intervertebral disc degeneration in adult patients with diabetes mellitus. PMID:25346805

  10. Neural correlates of single word reading in bilingual children and adults.

    PubMed

    Hernandez, Arturo E; Woods, Elizabeth A; Bradley, Kailyn A L

    2015-04-01

    The present study compared the neural correlates of language processing in children and adult Spanish-English bilinguals. Participants were asked to perform a visual lexical processing task in both Spanish and English while being scanned with fMRI. Both children and adults recruited a similar network of left hemisphere "language" areas and showed similar proficiency profiles in Spanish. In terms of behavior, adults showed better language proficiency in English relative to children. Furthermore, neural activity in adults was observed in the bilateral MTG. Age-related differences were observed in Spanish in the right MTG. The current results confirm the presence of neural activity in a set of left hemisphere areas in both adult and child bilinguals when reading words in each language. They also reveal that differences in neural activity are not entirely driven by changes in language proficiency during visual word processing. This indicates that both skill development and age can play a role in brain activity seen across development. PMID:25728012

  11. Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis

    PubMed Central

    Kumar, Vivek; Pandey, Ankita; Jahan, Sadaf; Shukla, Rajendra Kumar; Kumar, Dipak; Srivastava, Akriti; Singh, Shripriya; Rajpurohit, Chetan Singh; Yadav, Sanjay; Khanna, Vinay Kumar; Pant, Aditya Bhushan

    2016-01-01

    The plethora of literature has supported the potential benefits of Resveratrol (RV) as a life-extending as well as an anticancer compound. However, these two functional discrepancies resulted at different concentration ranges. Likewise, the role of Resveratrol on adult neurogenesis still remains controversial and less understood despite its well documented health benefits. To gather insight into the biological effects of RV on neurogenesis, we evaluated the possible effects of the compound on the proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of aged rats. Resveratrol exerted biphasic effects on NPCs; low concentrations (10 μM) stimulated cell proliferation mediated by increased phosphorylation of extracellular signal-regulated kinases (ERKs) and p38 kinases, whereas high concentrations (>20 μM) exhibited inhibitory effects. Administration of Resveratrol (20 mg/kg body weight) to adult rats significantly increased the number of newly generated cells in the hippocampus, with upregulation of p-CREB and SIRT1 proteins implicated in neuronal survival and lifespan extension respectively. We have successfully demonstrated that Resveratrol exhibits dose dependent discrepancies and at a lower concentration can have a positive impact on the proliferation, survival of NPCs and aged rat hippocampal neurogenesis implicating its potential as a candidate for restorative therapies against age related disorders. PMID:27334554

  12. Differential responses of Trans-Resveratrol on proliferation of neural progenitor cells and aged rat hippocampal neurogenesis.

    PubMed

    Kumar, Vivek; Pandey, Ankita; Jahan, Sadaf; Shukla, Rajendra Kumar; Kumar, Dipak; Srivastava, Akriti; Singh, Shripriya; Rajpurohit, Chetan Singh; Yadav, Sanjay; Khanna, Vinay Kumar; Pant, Aditya Bhushan

    2016-01-01

    The plethora of literature has supported the potential benefits of Resveratrol (RV) as a life-extending as well as an anticancer compound. However, these two functional discrepancies resulted at different concentration ranges. Likewise, the role of Resveratrol on adult neurogenesis still remains controversial and less understood despite its well documented health benefits. To gather insight into the biological effects of RV on neurogenesis, we evaluated the possible effects of the compound on the proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of aged rats. Resveratrol exerted biphasic effects on NPCs; low concentrations (10 μM) stimulated cell proliferation mediated by increased phosphorylation of extracellular signal-regulated kinases (ERKs) and p38 kinases, whereas high concentrations (>20 μM) exhibited inhibitory effects. Administration of Resveratrol (20 mg/kg body weight) to adult rats significantly increased the number of newly generated cells in the hippocampus, with upregulation of p-CREB and SIRT1 proteins implicated in neuronal survival and lifespan extension respectively. We have successfully demonstrated that Resveratrol exhibits dose dependent discrepancies and at a lower concentration can have a positive impact on the proliferation, survival of NPCs and aged rat hippocampal neurogenesis implicating its potential as a candidate for restorative therapies against age related disorders. PMID:27334554

  13. The neural underpinnings of reading skill in deaf adults.

    PubMed

    Emmorey, Karen; McCullough, Stephen; Weisberg, Jill

    2016-09-01

    We investigated word-level reading circuits in skilled deaf readers (N=14; mean reading age=19.5years) and less skilled deaf readers (N=14; mean reading age=12years) who were all highly proficient users of American Sign Language. During fMRI scanning, participants performed a semantic decision (concrete concept?), a phonological decision (two syllables?), and a false-font control task (string underlined?). No significant group differences were observed with the full participant set. However, an analysis with the 10 most and 10 least skilled readers revealed that for the semantic task (vs. control task), proficient deaf readers exhibited greater activation in left inferior frontal and middle temporal gyri than less proficient readers. No group differences were observed for the phonological task. Whole-brain correlation analyses (all participants) revealed that for the semantic task, reading ability correlated positively with neural activity in the right inferior frontal gyrus and in a region associated with the orthography-semantics interface, located anterior to the visual word form area. Reading ability did not correlate with neural activity during the phonological task. Accuracy on the semantic task correlated positively with neural activity in left anterior temporal lobe (a region linked to conceptual processing), while accuracy on the phonological task correlated positively with neural activity in left posterior inferior frontal gyrus (a region linked to syllabification processes during speech production). Finally, reading comprehension scores correlated positively with vocabulary and print exposure measures, but not with phonological awareness scores. PMID:27448530

  14. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  15. Neural Mechanisms Underlying Action Observation in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Virji-Babul, Naznin; Moiseev, Alexander; Cheung, Teresa; Weeks, Daniel J.; Cheyne, Douglas; Ribary, Urs

    2010-01-01

    Results of a magnetoencephalography (MEG) brain imaging study conducted to examine the cortical responses during action execution and action observation in 10 healthy adults and 8 age-matched adults with Down syndrome are reported. During execution, the motor responses were strongly lateralized on the ipsilateral rather than the contralateral side…

  16. Individual differences in the neural signature of subjective value among older adults.

    PubMed

    Halfmann, Kameko; Hedgcock, William; Kable, Joseph; Denburg, Natalie L

    2016-07-01

    Some healthy older adults show departures from standard decision-making patterns exhibited by younger adults. We asked if such departures are uniform or if heterogeneous aging processes can designate which older adults show differing decision patterns. Thirty-three healthy older adults with varying decision-making patterns on a complex decision task (the Iowa Gambling Task) completed an intertemporal choice task while undergoing functional magnetic resonance imaging. We examined whether value representation in the canonical valuation network differed across older adults based on complex decision-making ability. Older adults with advantageous decision patterns showed increased activity in the valuation network, including the ventromedial prefrontal cortex (VMPFC) and striatum. In contrast, older adults with disadvantageous decision patterns showed reduced or absent activation in the VMPFC and striatum, and these older adults also showed greater blood oxygen level dependent signal temporal variability in the striatum. Our results suggest that a reduced representation of value in the brain, possibly driven by increased neural noise, relates to suboptimal decision-making in a subset of older adults, which could translate to poor decision-making in many aspects of life, including finance, health and long-term care. Understanding the connection between suboptimal decision-making and neural value signals is a step toward mitigating age-related decision-making impairments. PMID:26089342

  17. Regulation of hypoxia-inducible factor-α isoforms and redox state by carotid body neural activity in rats

    PubMed Central

    Peng, Ying-Jie; Yuan, Guoxiang; Khan, Shakil; Nanduri, Jayasri; Makarenko, Vladislav V; Reddy, Vaddi Damodara; Vasavda, Chirag; Kumar, Ganesh K; Semenza, Gregg L; Prabhakar, Nanduri R

    2014-01-01

    Previous studies reported that chronic intermittent hypoxia (CIH) results in an imbalanced expression of hypoxia-inducible factor-α (HIF-α) isoforms and oxidative stress in rodents, which may be due either to the direct effect of CIH or indirectly via hitherto uncharacterized mechanism(s). As neural activity is a potent regulator of gene transcription, we hypothesized that carotid body (CB) neural activity contributes to CIH-induced HIF-α isoform expression and oxidative stress in the chemoreflex pathway. Experiments were performed on adult rats exposed to CIH for 10 days. Rats exposed to CIH exhibited: increased HIF-1α and decreased HIF-2α expression; increased NADPH oxidase 2 and decreased superoxide dismutase 2 expression; and oxidative stress in the nucleus tractus solitarius and rostral ventrolateral medulla as well as in the adrenal medulla (AM), a major end organ of the sympathetic nervous system. Selective ablation of the CB abolished these effects. In the AM, sympathetic activation by the CB chemoreflex mediates CIH-induced HIF-α isoform imbalance via muscarinic acetylcholine receptor-mediated Ca2+ influx, and the resultant activation of mammalian target of rapamycin pathway and calpain proteases. Rats exposed to CIH presented with hypertension, elevated sympathetic activity and increased circulating catecholamines. Selective ablation of either the CB (afferent pathway) or sympathetic innervation to the AM (efferent pathway) abolished these effects. These observations uncover CB neural activity-dependent regulation of HIF-α isoforms and the redox state by CIH in the central and peripheral nervous systems associated with the chemoreflex. PMID:24973414

  18. Comprehensive neural networks for guilty feelings in young adults.

    PubMed

    Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-01-15

    Feelings of guilt are associated with widespread self and social cognitions, e.g., empathy, moral reasoning, and punishment. Neural correlates directly related to the degree of feelings of guilt have not been detected, probably due to the small numbers of subjects, whereas there are growing numbers of neuroimaging studies of feelings of guilt. We hypothesized that the neural networks for guilty feelings are widespread and include the insula, inferior parietal lobule (IPL), amygdala, subgenual cingulate cortex (SCC), and ventromedial prefrontal cortex (vmPFC), which are essential for cognitions of guilt. We investigated the association between regional gray matter density (rGMD) and feelings of guilt in 764 healthy young students (422 males, 342 females; 20.7 ± 1.8 years) using magnetic resonance imaging and the guilty feeling scale (GFS) for the younger generation which comprises interpersonal situation (IPS) and rule-breaking situation (RBS) scores. Both the IPS and RBS were negatively related to the rGMD in the right posterior insula (PI). The IPS scores were negatively correlated with rGMD in the left anterior insula (AI), right IPL, and vmPFC using small volume correction. A post hoc analysis performed on the significant clusters identified through these analyses revealed that rGMD activity in the right IPL showed a significant negative association with the empathy quotient. These findings at the whole-brain level are the widespread comprehensive neural network regions for guilty feelings. Interestingly, the novel finding in this study is that the PI was implicated as a common region for feelings of guilt with interaction between the IPS and RBS. Additionally, the neural networks including the IPL were associated with empathy and with regions implicated in moral reasoning (AI and vmPFC), and punishment (AI). PMID:25462799

  19. Transplantation of Neural Stem Cells Cultured in Alginate Scaffold for Spinal Cord Injury in Rats

    PubMed Central

    Sharafkhah, Ali; Koohi-Hosseinabadi, Omid; Semsar-Kazerooni, Maryam

    2016-01-01

    Study Design This study investigated the effects of transplantation of alginate encapsulated neural stem cells (NSCs) on spinal cord injury in Sprague-Dawley male rats. The neurological functions were assessed for 6 weeks after transplantation along with a histological study and measurement of caspase-3 levels. Purpose The aim of this study was to discover whether NSCs cultured in alginate transplantation improve recovery from spinal cord injury. Overview of Literature Spinal cord injury is one of the leading causes of disability and it has no effective treatment. Spinal cord injury can also cause sensory impairment. With an impetus on using stem cells therapy in various central nervous system settings, there is an interest in using stem cells for addressing spinal cord injury. Neural stem cell is one type of stem cells that is able to differentiate to all three neural lineages and it shows promise in spinal injury treatment. Furthermore, a number of studies have shown that culturing NSCs in three-dimensional (3D) scaffolds like alginate could enhance neural differentiation. Methods The NSCs were isolated from 14-day-old rat embryos. The isolated NSCs were cultured in growth media containing basic fibroblast growth factor and endothelial growth factor. The cells were characterized by differentiating to three neural lineages and they were cultured in an alginate scaffold. After 7 days the cells were encapsulated and transplanted in a rat model of spinal cord injury. Results Our data showed that culturing in an alginate 3D scaffold and transplantation of the NSCs could improve neurological outcome in a rat model of spinal cord injury. The inflammation scores and lesion sizes and also the activity of caspase-3 (for apoptosis evaluation) were less in encapsulated neural stem cell transplantation cases. Conclusions Transplantation of NSCs that were cultured in an alginate scaffold led to a better clinical and histological outcome for recovery from spinal cord injury in

  20. The Neural Basis of Sustained and Transient Attentional Control in Young Adults with ADHD

    ERIC Educational Resources Information Center

    Banich, Marie T.; Burgess, Gregory C.; Depue, Brendan E.; Ruzic, Luka; Bidwell, L. Cinnamon; Hitt-Laustsen, Sena; Du, Yiping P.; Willcutt, Erik G.

    2009-01-01

    Differences in neural activation during performance on an attentionally demanding Stroop task were examined between 23 young adults with ADHD carefully selected to not be co-morbid for other psychiatric disorders and 23 matched controls. A hybrid blocked/single-trial design allowed for examination of more sustained vs. more transient aspects of…

  1. Neural Correlates of Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Vasic, Nenad; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Wolf, Robert Christian

    2008-01-01

    Behavioral studies indicate deficits in phonological working memory (WM) and executive functioning in dyslexics. However, little is known about the underlying functional neuroanatomy. In the present study, neural correlates of WM in adolescents and young adults with dyslexia were investigated using event-related functional magnetic resonance…

  2. Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice

    PubMed Central

    Mozafari, Sabah; Laterza, Cecilia; Roussel, Delphine; Bachelin, Corinne; Marteyn, Antoine; Deboux, Cyrille; Martino, Gianvito; Evercooren, Anne Baron-Van

    2015-01-01

    Induced pluripotent stem cell–derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, the therapeutic potential of reprogrammed cells has been evaluated in neonatal demyelinating models. However, the repair efficacy and safety of these cells has not been well addressed in the demyelinated adult CNS, which has decreased cell plasticity and scarring. Moreover, it is not clear if these induced pluripotent–derived cells have the same reparative capacity as physiologically committed CNS-derived precursors. Here, we performed a side-by-side comparison of CNS-derived and skin-derived neural precursors in culture and following engraftment in murine models of adult spinal cord demyelination. Grafted induced neural precursors exhibited a high capacity for survival, safe integration, migration, and timely differentiation into mature bona fide oligodendrocytes. Moreover, grafted skin–derived neural precursors generated compact myelin around host axons and restored nodes of Ranvier and conduction velocity as efficiently as CNS-derived precursors while outcompeting endogenous cells. Together, these results provide important insights into the biology of reprogrammed cells in adult demyelinating conditions and support use of these cells for regenerative biomedicine of myelin diseases that affect the adult CNS. PMID:26301815

  3. Peripubertal ovariectomy influences thymic adrenergic network plasticity in adult rats.

    PubMed

    Pilipović, Ivan; Vujnović, Ivana; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Kosec, Duško; Stojić-Vukanić, Zorica; Leposavić, Gordana

    2016-08-15

    The study investigated the influence of peripubertal ovariectomy on the thymic noradrenaline (NA) concentration, and the thymocyte NA content and β2- and α1-adrenoceptor (AR) expression in adult 2- and 11-month-old rats. In control rats, the thymic NA concentration increased with age. This increase reflected rise in the density of catecholamine (CA)-containing fluorescent nerve fibers and cells and their CA content. Additionally, the average β2- and α1-AR thymocyte surface density changed in the opposite direction with age; the density of β2-AR decreased, whereas that of α1-AR increased. Ovariectomy diminished the thymic NA concentration in 2-month-old rats. This reflected the decrease in the density of fluorescent nerve fibers, and CA content in fluorescent nerve fibers and non-lymphoid cells, since the thymocyte NA content was increased in ovariectomized (Ox) rats. Estrogen supplementation prevented the ovariectomy-induced changes. In Ox rats, the density of CA-synthesizing nerve fibers and non-lymphoid cells diminished with age. To the contrary, NA content in thymocytes increased with age, but it did not exceed that in 11-month-old controls. Additionally, ovariectomy diminished the average thymocyte surface density of β2-ARs, but it increased that of α1-ARs in 2-month-old-rats (due to estrogen, and estrogen and progesterone deficiency, respectively). These changes, despite of the rise in circulating estrogen level post-ovariectomy, remained stable with age. This most likely reflected a decreased sensitivity to estrogen action, as a consequence of the hormone misprinting in peripubertal age. The analysis of thymocyte proliferation in culture suggested that age- and ovariectomy-induced alterations in thymocyte NA synthesis and AR expression altered NA autocrine/paracrine action on thymocytes. In conclusion, the study indicates that the ovarian hormone deficiency in peripubertal age affects ovarian steroid-dependent remodeling of thymic adrenergic

  4. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    SciTech Connect

    Khalifa, Shaden A.M.; Medina, Philippe de; Erlandsson, Anna; El-Seedi, Hesham R.; Silvente-Poirot, Sandrine; Poirot, Marc

    2014-04-11

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain.

  5. BMP3 expression in the adult rat CNS.

    PubMed

    Yamashita, Kanna; Mikawa, Sumiko; Sato, Kohji

    2016-07-15

    Bone morphogenetic protein-3 (BMP3) is a very unique member of the TGF-β superfamily, because it functions as an antagonist to both the canonical BMP and activin pathways and plays important roles in multiple biological events. Although BMP3 expression has been described in the early development of the kidney, intestine and bone, little information is available for BMP3 expression in the central nervous system (CNS). We, thus, investigated BMP3 expression in the adult rat CNS using immunohistochemistry. BMP3 was intensely expressed in most neurons and their axons. Furthermore, we found that astrocytes and ependymal cells also express BMP3 protein. These data indicate that BMP3 is widely expressed throughout the adult CNS, and its abundant expression in the adult brain strongly supports the idea that BMP3 plays important roles in the adult brain. PMID:27130896

  6. Stroke Increases Neural Stem Cells and Angiogenesis in the Neurogenic Niche of the Adult Mouse

    PubMed Central

    Zhang, Rui Lan; Chopp, Michael; Roberts, Cynthia; Liu, Xianshuang; Wei, Min; Nejad-Davarani, Siamak P.; Wang, Xinli; Zhang, Zheng Gang

    2014-01-01

    The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction. PMID:25437857

  7. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    SciTech Connect

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  8. Large-scale live imaging of adult neural stem cells in their endogenous niche

    PubMed Central

    Dray, Nicolas; Bedu, Sébastien; Vuillemin, Nelly; Alunni, Alessandro; Coolen, Marion; Krecsmarik, Monika; Supatto, Willy; Beaurepaire, Emmanuel; Bally-Cuif, Laure

    2015-01-01

    Live imaging of adult neural stem cells (aNSCs) in vivo is a technical challenge in the vertebrate brain. Here, we achieve long-term imaging of the adult zebrafish telencephalic neurogenic niche and track a population of >1000 aNSCs over weeks, by taking advantage of fish transparency at near-infrared wavelengths and of intrinsic multiphoton landmarks. This methodology enables us to describe the frequency, distribution and modes of aNSCs divisions across the entire germinal zone of the adult pallium, and to highlight regional differences in these parameters. PMID:26395477

  9. Neural Correlates of Letter Reversal in Children and Adults

    PubMed Central

    Kalra, Priya; Yee, Debbie; Sinha, Pawan; Gabrieli, John D. E.

    2014-01-01

    Children often make letter reversal errors when first learning to read and write, even for letters whose reversed forms do not appear in normal print. However, the brain basis of such letter reversal in children learning to read is unknown. The present study compared the neuroanatomical correlates (via functional magnetic resonance imaging) and the electrophysiological correlates (via event-related potentials or ERPs) of this phenomenon in children, ages 5–12, relative to young adults. When viewing reversed letters relative to typically oriented letters, adults exhibited widespread occipital, parietal, and temporal lobe activations, including activation in the functionally localized visual word form area (VWFA) in left occipito-temporal cortex. Adults exhibited significantly greater activation than children in all of these regions; children only exhibited such activation in a limited frontal region. Similarly, on the P1 and N170 ERP components, adults exhibited significantly greater differences between typical and reversed letters than children, who failed to exhibit significant differences between typical and reversed letters. These findings indicate that adults distinguish typical and reversed letters in the early stages of specialized brain processing of print, but that children do not recognize this distinction during the early stages of processing. Specialized brain processes responsible for early stages of letter perception that distinguish between typical and reversed letters may develop slowly and remain immature even in older children who no longer produce letter reversals in their writing. PMID:24859328

  10. Assigning Function to Adult-Born Neurons: A Theoretical Framework for Characterizing Neural Manipulation of Learning

    PubMed Central

    Hersman, Sarah; Rodriguez Barrera, Vanessa; Fanselow, Michael

    2016-01-01

    Neuroscientists are concerned with neural processes or computations, but these may not be directly observable. In the field of learning, a behavioral procedure is observed to lead to performance outcomes, but differing inferences on underlying internal processes can lead to difficulties in interpreting conflicting results. An example of this challenge is how many functions have been attributed to adult-born granule cells in the dentate gyrus. Some of these functions were suggested by computational models of the properties of these neurons, while others were hypothesized after manipulations of adult-born neurons resulted in changes to behavioral metrics. This review seeks to provide a framework, based in learning theory classification of behavioral procedures, of the processes that may be underlying behavioral results after manipulating procedure and observing performance. We propose that this framework can serve to clarify experimental findings on adult-born neurons as well as other classes of neural manipulations and their effects on behavior. PMID:26778981

  11. Low doses of memantine disrupt memory in adult rats.

    PubMed

    Creeley, Catherine; Wozniak, David F; Labruyere, Joanne; Taylor, George T; Olney, John W

    2006-04-12

    Memantine, a drug recently approved for treatment of Alzheimer's disease, has been characterized as a unique NMDA antagonist that confers protection against excitotoxic neurodegeneration without the serious side effects that other NMDA antagonists are known to cause. In the present study, we determined what dose of memantine is required to protect the adult rat brain against an NMDA receptor-mediated excitotoxic process and then tested that dose and a range of lower doses to determine whether the drug in this dose range is associated with significant side effects. Consistent with previous research, we found that memantine confers a neuroprotective effect beginning at an intraperitoneal dose of 20 mg/kg, a dose that we found, contrary to previous reports, produces locomotor disturbances severe enough to preclude testing for learning and memory effects. We then determined that, at intraperitoneal doses of 10 and 5 mg/kg, memantine disrupts both memory and locomotor behaviors. Rats treated with these doses performed at control-like levels in learning a hole-board task but were significantly impaired in demonstrating what they had learned when tested 24 h later. This impairment of memory retention was not state dependent in that it was demonstrable regardless of whether the rats were or were not exposed to memantine on the day of retention testing. We conclude that, in the adult rat, memantine behaves like other NMDA antagonists in that it is neuroprotective only at doses that produce intolerable side effects, including memory impairment. PMID:16611808

  12. AMNESIA FOR EARLY LIFE STRESS DOES NOT PRECLUDE THE ADULT DEVELOPMENT OF PTSD SYMPTOMS IN RATS

    PubMed Central

    Poulos, Andrew M.; Reger, Maxine; Mehta, Nehali; Zhuravka, Irina; Sterlace, Sarah S.; Gannam, Camille; Hovda, David A.; Giza, Christopher C.; Fanselow, Michael

    2013-01-01

    Background Traumatic experience can result in life-long changes in the ability to cope with future stressors and emotionally salient events. These experiences, particularly during early development are a significant risk factor for later life anxiety disorders such as post-traumatic stress disorder (PTSD). However, because traumatic experience typically results in strong episodic memories, it is not known whether such long-term memories are necessary for particular features of PTSD such as enhanced fear and anxiety. Here we used a fear conditioning procedure in juvenile rats prior to maturation of the neural systems supporting declarative memory to assess the necessity of early memory to the later life development of PTSD related symptoms. Methods Nineteen-day old rats were exposed to unpredictable and inescapable footshocks and fear memory for the shock context was assessed during adulthood. Thereafter, adult animals were either exposed to single-trial fear conditioning, elevated plus-maze or sacrificed for basal diurnal corticosterone and quantification of neuronal glucocorticoid (G-R) and Neuropeptide Y receptors. Results Early trauma exposed rats displayed stereotypic footshock reactivity, yet by adulthood, hippocampus-dependent contextual fear related memory was absent. However, adult rats showed sensitized fear learning, aberrant basal circadian fluctuations of corticosterone, increased amygdalar G-R, decreased time spent in the open arm of an elevated plus maze and an odor aversion associated with early-life footshocks. Conclusions These results suggest that traumatic experience during developmental periods of hippocampal immaturity can promote lifelong changes in symptoms and neuropathology associated with human PTSD even if there is no explicit memory of the early trauma. PMID:24231200

  13. 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.

  14. 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…

  15. Adolescent Intermittent Ethanol Exposure Is Associated with Increased Risky Choice and Decreased Dopaminergic and Cholinergic Neuron Markers in Adult Rats

    PubMed Central

    Boutros, Nathalie; Semenova, Svetlana; Liu, Wen; Crews, Fulton T.

    2015-01-01

    Background: Binge drinking is prevalent during adolescence and may have effects on the adult brain and behavior. The present study investigated whether adolescent intermittent ethanol exposure alters adult risky choice and prefrontal dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar rats. Methods: Adolescent (postnatal day 28–53) rats were administered 5g/kg of 25% (vol/vol) ethanol 3 times/d in a 2-days–on/2-days–off exposure pattern. In adulthood, risky choice was assessed in the probability discounting task with descending and ascending series of large reward probabilities and after acute ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices, and choline acetyltransferase, a marker of cholinergic neurons, in the basal forebrain. Results: All of the rats preferred the large reward when it was delivered with high probability. When the large reward became unlikely, control rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol-exposed rats continued to prefer the risky alternative. Acute ethanol had no effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic cortex only) and choline acetyltransferase immunoreactivity levels were decreased in adolescent intermittent ethanol-exposed rats compared with controls. Risky choice was negatively correlated with choline acetyltransferase, implicating decreased forebrain cholinergic activity in risky choice. Conclusions: The decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity suggest that adolescent intermittent ethanol exposure has enduring neural effects that may lead to altered adult behaviors, such as increased risky decision making. In humans, increased risky decision making could lead to maladaptive, potentially harmful consequences. PMID:25612895

  16. Neural correlates of conceptual object priming in young and older adults: An event-related fMRI study

    PubMed Central

    Ballesteros, Soledad; Bischof, Gérard N.; Goh, Joshua O.; Park, Denise C.

    2012-01-01

    In this event-related fMRI study, we investigated age-related differences in brain activity associated with conceptual repetition priming in young and older adults. Participants performed a speeded “living/non-living” classification task with three repetitions of familiar objects. Both young and older adults showed a similar magnitude of behavioral priming to repeated objects and evidencing repetition-related activation reductions in fusiform gyrus, superior occipital, middle and inferior temporal cortex, as well as inferior frontal and insula regions. The neural priming effect in young adults was extensive and continued through both the second and third stimulus repetitions, whereas neural priming in older adults was markedly attenuated and reached floor at the second repetition. In young adults, greater neural priming in multiple brain regions correlated with greater behavioral facilitation whereas in older adults, only activation reduction in the left inferior frontal correlated with faster behavioral responses. These findings provide evidence for altered neural priming in older adults despite preserved behavioral priming, and suggest the possibility that age-invariant behavioral priming is observed as a result of more sustained neural processing of stimuli in older adults which may be a form of compensatory neural activity. PMID:23102512

  17. Neural correlates of conceptual object priming in young and older adults: an event-related functional magnetic resonance imaging study.

    PubMed

    Ballesteros, Soledad; Bischof, Gérard N; Goh, Joshua O; Park, Denise C

    2013-04-01

    In this event-related functional magnetic resonance imaging study, we investigated age-related differences in brain activity associated with conceptual repetition priming in young and older adults. Participants performed a speeded "living/nonliving" classification task with 3 repetitions of familiar objects. Both young and older adults showed a similar magnitude of behavioral priming to repeated objects and evidenced repetition-related activation reductions in fusiform gyrus, superior occipital, middle, and inferior temporal cortex, and inferior frontal and insula regions. The neural priming effect in young adults was extensive and continued through both the second and third stimulus repetitions, and neural priming in older adults was markedly attenuated and reached floor at the second repetition. In young adults, greater neural priming in multiple brain regions correlated with greater behavioral facilitation and in older adults, only activation reduction in the left inferior frontal correlated with faster behavioral responses. These findings provide evidence for altered neural priming in older adults despite preserved behavioral priming, and suggest the possibility that age-invariant behavioral priming is observed as a result of more sustained neural processing of stimuli in older adults which might be a form of compensatory neural activity. PMID:23102512

  18. GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat.

    PubMed

    Ayala-Sarmiento, Alberto E; Estudillo, Enrique; Pérez-Sánchez, Gilberto; Sierra-Sánchez, Arturo; González-Mariscal, Lorenza; Martínez-Fong, Daniel; Segovia, José

    2016-09-01

    Growth arrest specific 1 (GAS1) is a GPI-anchored protein that inhibits proliferation when overexpressed in tumors but during development it promotes proliferation and survival of different organs and tissues. This dual ability is caused by its capacity to interact both by inhibiting the signaling induced by the glial cell line-derived neurotrophic factor and by facilitating the activity of the sonic hedgehog pathway. GAS1 is expressed as membrane bound in different organs and as a secreted form by glomerular mesangial cells. In the developing central nervous system, GAS1 is found in neural progenitors; however, it continues to be expressed in the adult brain. Here, we demonstrate that soluble GAS1 is present in the cerebrospinal fluid (CSF) and it is expressed in the choroid plexus (CP) of the adult rat, the main producer of CSF. Additionally, we confirm the presence of GAS1 in blood plasma and liver of the adult rat, the principal source of blood plasma proteins. The pattern of expression of GAS1 is perivascular in both the CP and the liver. In vitro studies show that the fibroblast cell line NIH/3T3 expresses one form of GAS1 and releases two soluble forms into the supernatant. Briefly, in the present work, we show the presence of GAS1 in adult rat body fluids focusing in the CSF and the CP, and suggest that secreted GAS1 exists as two different isoforms. PMID:27225491

  19. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

    PubMed Central

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  20. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors.

    PubMed

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  1. Stimulation of dendrogenesis and neural maturation in adult mammals.

    PubMed

    Soto-Vázquez, Ramón; Labastida-López, Carlos; Romero-Castello, Samuel; Benítez-King, Gloria; Parra-Cervantes, Patricia

    2016-05-01

    This work is the result of a technical research patent on dendritogenesis and neuronal maturation, in which the existence was determined of patent documents involving the use of melatonin for the treatment of anxiety, obesity and related diseases of the peripheral and CNS. In this study, an analysis of the state of the art in order to collect technical and scientific elements for the drafting of a new patent on the use of the melatonin molecule in stimulating neuronal maturation in dendritogenesis and mammals was conducted in adults. This study is based on an invention related with this novel use of melatonin. PMID:27087552

  2. Using strategic movement to calibrate a neural compass: a spiking network for tracking head direction in rats and robots.

    PubMed

    Stratton, Peter; Milford, Michael; Wyeth, Gordon; Wiles, Janet

    2011-01-01

    The head direction (HD) system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular) inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that 'grounding' of modelled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology), and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex. PMID:21991332

  3. Using Strategic Movement to Calibrate a Neural Compass: A Spiking Network for Tracking Head Direction in Rats and Robots

    PubMed Central

    Stratton, Peter; Milford, Michael; Wyeth, Gordon; Wiles, Janet

    2011-01-01

    The head direction (HD) system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular) inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that ‘grounding’ of modelled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology), and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex. PMID:21991332

  4. Development of exoskeletal robotic limbs for a rat controlled by neural signals based on a vehicular neuro-robotic platform RatCar.

    PubMed

    Fukayama, Osamu; Otsuka, Hiroshi; Hashimoto, Ryuta; Suzuki, Takafumi; Mabuchi, Kunihiko

    2012-01-01

    A pair of exoskeletal limbs for a rat has been developed based on a vehicular Brain-Machine Interface "Rat-Car". The "RatCar" is a whole-body motor prosthesis system for a rat developed by the authors, estimating locomotion velocity according to neural signals pattern to move the rat body by the vehicle instead of its original limbs. In this paper, exoskeletal limbs have displaced the wheels for more natural modality of body control. The system was tested by applying peripheral nerve signals from a behaving rat. PMID:23366238

  5. 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

    PubMed Central

    Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J.; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario

    2016-01-01

    Background: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. Methodology: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. Results: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. Conclusions: This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical

  6. Up-regulation of DRP-3 long isoform during the induction of neural progenitor cells by glutamate treatment in the ex vivo rat retina

    SciTech Connect

    Tokuda, Kazuhiro; Kuramitsu, Yasuhiro; Byron, Baron; Kitagawa, Takao; Tokuda, Nobuko; Kobayashi, Daiki; Nagayama, Megumi; Araki, Norie; Sonoda, Koh-Hei; Nakamura, Kazuyuki

    2015-08-07

    Glutamate has been shown to induce neural progenitor cells in the adult vertebrate retina. However, protein dynamics during progenitor cell induction by glutamate are not fully understood. To identify specific proteins involved in the process, we employed two-dimensional electrophoresis-based proteomics on glutamate untreated and treated retinal ex vivo sections. Rat retinal tissues were incubated with 1 mM glutamate for 1 h, followed by incubation in glutamate-free media for a total of 24 h. Consistent with prior reports, it was found that mitotic cells appeared in the outer nuclear layer without any histological damage. Immunohistological evaluations and immunoblotting confirmed the emergence of neuronal progenitor cells in the mature retina treated with glutamate. Proteomic analysis revealed the up-regulation of dihydropyrimidinase-related protein 3 (DRP-3), DRP-2 and stress-induced-phosphoprotein 1 (STIP1) during neural progenitor cell induction by glutamate. Moreover, mRNA expression of DRP-3, especially, its long isoform, robustly increased in the treated retina compared to that in the untreated retina. These results may indicate that glutamate induces neural progenitor cells in the mature rat retina by up-regulating the proteins which mediate cell mitosis and neurite growth. - Highlights: • Glutamate induced neuronal progenitor cells in the mature rat retina. • Proteomic analysis revealed the up-regulation of DRP-3, DRP-2 and STIP1. • mRNA expression of DRP-3, especially, its long isoform, robustly increased.

  7. Isolation of neural crest derived chromaffin progenitors from adult adrenal medulla.

    PubMed

    Chung, Kuei-Fang; Sicard, Flavie; Vukicevic, Vladimir; Hermann, Andreas; Storch, Alexander; Huttner, Wieland B; Bornstein, Stefan R; Ehrhart-Bornstein, Monika

    2009-10-01

    Chromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Unlike the closely-related sympathetic neurons, a subpopulation of proliferation-competent cells exists even in the adult. Here, we describe the isolation, expansion, and in vitro characterization of proliferation-competent progenitor cells from the bovine adrenal medulla. Similar to neurospheres, these cells, when prevented from adherence to the culture dish, grew in spheres, which we named chromospheres. These chromospheres were devoid of mRNA specific for smooth muscle cells (MYH11) or endothelial cells (PECAM1). During sphere formation, markers for differentiated chromaffin cells, such as phenylethanolamine-N-methyl transferase, were downregulated while neural progenitor markers nestin, vimentin, musashi 1, and nerve growth factor receptor, as well as markers of neural crest progenitor cells such as Sox1 and Sox9, were upregulated. Clonal analysis and bromo-2'-deoxyuridine-incorporation analysis demonstrated the self-renewing capacity of chromosphere cells. Differentiation protocols using NGF and BMP4 or dexamethasone induced neuronal or endocrine differentiation, respectively. Electrophysiological analyses of neural cells derived from chromospheres revealed functional properties of mature nerve cells, such as tetrodotoxin-sensitive sodium channels and action potentials. Our study provides evidence that proliferation and differentiation competent chromaffin progenitor cells can be isolated from adult adrenal medulla and that these cells might harbor the potential for the treatment of neurodegenerative diseases, such as Parkinson's disease. PMID:19609938

  8. Effects of addictive drugs on adult neural stem/progenitor cells.

    PubMed

    Xu, Chi; Loh, Horace H; Law, Ping-Yee

    2016-01-01

    Neural stem/progenitor cells (NSPCs) undergo a series of developmental processes before giving rise to newborn neurons, astrocytes and oligodendrocytes in adult neurogenesis. During the past decade, the role of NSPCs has been highlighted by studies on adult neurogenesis modulated by addictive drugs. It has been proven that these drugs regulate the proliferation, differentiation and survival of adult NSPCs in different manners, which results in the varying consequences of adult neurogenesis. The effects of addictive drugs on NSPCs are exerted via a variety of different mechanisms and pathways, which interact with one another and contribute to the complexity of NSPC regulation. Here, we review the effects of different addictive drugs on NSPCs, and the related experimental methods and paradigms. We also discuss the current understanding of major signaling molecules, especially the putative common mechanisms, underlying such effects. Finally, we review the future directions of research in this area. PMID:26468052

  9. Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

    PubMed Central

    Knobloch, Marlen; Braun, Simon M. G.; Zurkirchen, Luis; von Schoultz, Carolin; Zamboni, Nicola; Arauzo-Bravo, Marcos J.; Kovacs, Werner J.; Karalay, Özlem; Suter, Ueli; Machado, Raquel A. C.; Roccio, Marta; Lutolf, Matthias P.; Semenkovich, Clay F.; Jessberger, Sebastian

    2013-01-01

    Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain1. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis2, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism3–5, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA6, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation. PMID:23201681

  10. Neural stem cells, adult neurogenesis, and galectin-1: from bench to bedside.

    PubMed

    Sakaguchi, Masanori; Okano, Hideyuki

    2012-07-01

    Neural stem cells (NSCs) in the adult brain have been a consistent focus of biomedical research largely because of their potential clinical application. To fully exploit this potential, the molecular mechanisms that regulate NSCs must be clarified. Several lines of evidence show that a multifunctional protein, Galectin-1, is expressed and has a functional role in a subset of adult NSCs. Researchers, including our group, have explored the physiological role of Galectin-1 in NSCs and its application in the treatment of animal models of neurological disorders such as brain ischemia and spinal cord injury. Here, we summarize what is currently known regarding the role of Galectin-1 in adult NSCs. Furthermore, we discuss current issues in researching the role of Galectin-1 in adult NSCs under both physiological and pathological conditions. PMID:22488739

  11. Mesenteric lymph flow in adult and aged rats.

    PubMed

    Akl, Tony J; Nagai, Takashi; Coté, Gerard L; Gashev, Anatoliy A

    2011-11-01

    The objective of study was to evaluate the aging-associated changes, contractile characteristics of mesenteric lymphatic vessels (MLV), and lymph flow in vivo in male 9- and 24-mo-old Fischer-344 rats. Lymphatic diameter, contraction amplitude, contraction frequency, and fractional pump flow, lymph flow velocity, wall shear stress, and minute active wall shear stress load were determined in MLV in vivo before and after N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) application at 100 μM. The active pumping of the aged rat MLV in vivo was found to be severely depleted, predominantly through the aging-associated decrease in lymphatic contractile frequency. Such changes correlate with enlargement of aged MLV, which experienced much lower minute active shear stress load than adult vessels. At the same time, pumping in aged MLV in vivo may be rapidly increased back to levels of adult vessels predominantly through the increase in contraction frequency induced by nitric oxide (NO) elimination. Findings support the idea that in aged tissues surrounding the aged MLV, the additional source of some yet unlinked lymphatic contraction-stimulatory metabolites is counterbalanced or blocked by NO release. The comparative analysis of the control data obtained from experiments with both adult and aged MLV in vivo and from isolated vessel-based studies clearly demonstrated that ex vivo isolated lymphatic vessels exhibit identical contractile characteristics to lymphatic vessels in vivo. PMID:21873496

  12. GABA's Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches

    PubMed Central

    Young, Stephanie Z.; Bordey, Angélique

    2010-01-01

    Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery that controls the proliferation of tumor cells and perhaps tumor stem cells. Here, we will discuss GABA's presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity. PMID:19509127

  13. Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone.

    PubMed

    Calzolari, Filippo; Michel, Julia; Baumgart, Emily Violette; Theis, Fabian; Götz, Magdalena; Ninkovic, Jovica

    2015-04-01

    We analyzed the progeny of individual neural stem cells (NSCs) of the mouse adult subependymal zone (SEZ) in vivo and found a markedly fast lineage amplification, as well as limited NSC self-renewal and exhaustion in a few weeks. We further unraveled the mechanisms of neuronal subtype generation, finding that a higher proportion of NSCs were dedicated to generate deep granule cells in the olfactory bulb and that larger clones were produced by these NSCs. PMID:25730673

  14. Speech Sound Processing Deficits and Training-Induced Neural Plasticity in Rats with Dyslexia Gene Knockdown

    PubMed Central

    Centanni, Tracy M.; Chen, Fuyi; Booker, Anne M.; Engineer, Crystal T.; Sloan, Andrew M.; Rennaker, Robert L.; LoTurco, Joseph J.; Kilgard, Michael P.

    2014-01-01

    In utero RNAi of the dyslexia-associated gene Kiaa0319 in rats (KIA-) degrades cortical responses to speech sounds and increases trial-by-trial variability in onset latency. We tested the hypothesis that KIA- rats would be impaired at speech sound discrimination. KIA- rats needed twice as much training in quiet conditions to perform at control levels and remained impaired at several speech tasks. Focused training using truncated speech sounds was able to normalize speech discrimination in quiet and background noise conditions. Training also normalized trial-by-trial neural variability and temporal phase locking. Cortical activity from speech trained KIA- rats was sufficient to accurately discriminate between similar consonant sounds. These results provide the first direct evidence that assumed reduced expression of the dyslexia-associated gene KIAA0319 can cause phoneme processing impairments similar to those seen in dyslexia and that intensive behavioral therapy can eliminate these impairments. PMID:24871331

  15. Human-derived neural progenitors functionally replace astrocytes in adult mice

    PubMed Central

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair. PMID:25642771

  16. Role of the neural pathway from hindbrain to hypothalamus in the regulation of energy homeostasis in rats.

    PubMed

    Utoyama, Maiko; Akieda-Asai, Sayaka; Koda, Shuichi; Nunoi, Hiroyuki; Date, Yukari

    2016-02-12

    Recent evidence suggests that neural pathways from the hindbrain to the hypothalamus are important for informing the hypothalamus of the body's condition with regard to energy metabolism. Here we examined energy metabolism in rats with transections of the midbrain that severed the neural pathway from the hindbrain to the hypothalamus, and then investigated the levels of various molecules associated with control of energy metabolism in these rats. Food intake and body weight were higher in the midbrain-transected rats than in sham-operated rats. In addition, the midbrain-transected rats showed insulin resistance and hyperleptinemia. Furthermore, the hypothalamic mRNA levels of anorectic proopiomelanocortin and cocaine- and amphetamine-related transcript were significantly lower in midbrain-transected rats than in sham-operated rats. Our findings elucidate the mechanisms of food intake and energy balance from the perspective of multifactorial regulatory systems that underlie functions such as neurohormonal integration. PMID:26773865

  17. Perinatal undernutrition programmes thyroid function in the adult rat offspring.

    PubMed

    Ayala-Moreno, Rosario; Racotta, Radu; Anguiano, Brenda; Aceves, Carmen; Quevedo, Lucía

    2013-12-01

    Increasing evidence suggests that alterations in early nutrition programme physiological changes in adulthood. In the present study, we determined the effects of undernutrition during gestation and lactation on the programming of thyroid function in adult rat offspring. Perinatal undernutrition was achieved by a 40% food restriction in female Wistar rats from the mating day to weaning. On postpartum day 21, the offspring of the control and food-restricted dams were weaned and given free access to a commercial diet until adulthood. The results showed that undernourished rats exhibited decreased 3,5,3'-triiodothyronine (T3) levels but had normal thyroxine (T4) and thyrotropin (TSH) levels at weaning; on day 90, these rats displayed a significant flip, exhibiting normalised T3 (total and free) and total T4 levels, but low free T4 and persistently higher TSH levels, which were maintained even on postnatal day 140. This profile was accompanied by a scarce fat depot, a lower RMR and an exacerbated sympathetic brown adipose tissue (BAT) tone (deiodinase type 2 expression) in basal conditions. Moreover, when a functional challenge (cold exposure) was applied, the restricted group exhibited partial changes in TSH (29 v. 100%) and T4 (non-response v. 17%) levels, a significant decrease in leptin levels (75 v. 32%) and the maintenance of a sympathetic BAT over-response (higher noradrenaline levels) in comparison with the control group. The findings of the present study suggest that undernutrition during the perinatal period produces permanent changes in the hypothalamus-pituitary-thyroid axis with consequent low body weight and decreased RMR and facultative thermogenesis. We hypothesise that these changes predispose individuals to exhibiting adult subclinical hypothyroidism. PMID:23800456

  18. Isolation and characterization of neural stem cells from the neonatal rat cochlear nucleus.

    PubMed

    Rak, Kristen; Wasielewski, Natalia V; Radeloff, Andreas; Völkers, Johannes; Scherzed, Agmal; Jablonka, Sibylle; Hagen, Rudolf; Mlynski, Robert

    2011-03-01

    Neural stem cells have been identified in multiple parts of the postnatal mammalian brain, as well as in the inner ear. No investigation of potential neural stem cells in the cochlear nucleus has yet been performed. The aim of this study was to investigate potential neural stem cells from the cochlear nucleus by neurosphere assay and in histological sections to prove their capacity for self-renewal and for differentiation into progenitor cells and cells of the neuronal lineage. For this purpose, cells of the cochlear nucleus of postnatal day 6 rats were isolated and cultured for generation of primary neurospheres. Spheres were dissociated and cells analyzed for capacity for mitosis and differentiation. Cell division was detected by cell-counting assay and BrdU incorporation. Differentiated neural progenitor cells showed distinct labeling for Nestin and for Atoh1. Positive staining of ß-III Tubulin, glial fibrillary acid protein (GFAP) and myelin basic protein (MBP) showed differentiation into neurons, astrocytes and oligodendrocytes. Furthermore, Nestin- and BrdU-labeled cells could also be detected in histological sections. In conclusion, the isolated cells from the cochlear nucleus presented all the features of neural stem cells: cell division, presence of progenitor cells and differentiation into different cells of the neuronal lineage. The existence of neural stem cells may add to the understanding of developmental features in the cochlear nucleus. PMID:21258945

  19. Long-term survival and integration of porcine expanded neural precursor cell grafts in a rat model of Parkinson's disease.

    PubMed

    Harrower, T P; Tyers, P; Hooks, Y; Barker, R A

    2006-01-01

    Porcine fetal neural tissue has been considered as an alternative source to human allografts for transplantation in neurodegenerative disorders by virtue of the fact that it can overcome the ethical and practical difficulties using human fetal neural tissue. However, primary porcine neural xenografts are rejected while porcine expanded neural precursor neural cells (PNPCs) seem to be less immunogenic and thus survive better [Armstrong, R.J., Harrower, T.P., Hurelbrink, C.B., McLaughin, M., Ratcliffe, E.L., Tyers, P., Richards, A., Dunnett, S.B., Rosser, A.E., Barker, R.A., 2001a. Porcine neural xenografts in the immunocompetent rat: immune response following grafting of expanded neural precursor cells. Neuroscience 106, 201-216]. In this study, we extended these observations to investigate the long-term survival of such transplants in immunosuppressed rats. Unilateral 6 OHDA lesioned rats received grafts into the dopamine denervated striatum of either primary porcine fetal neural tissue dissected from the E26 cortex or cortically derived neural stem cells which had been derived from the same source but expanded in vitro for 21 days. All cortically derived neural stem cell grafts survived up to 5 months in contrast to the poor survival of primary porcine xenografts. Histological analysis demonstrated good graft integration with fibers extending into the surrounding host tissue including white matter with synapse formation, and in addition there was evidence of host vascularization and myelinated fibers within the graft area. This study has therefore shown for the first time the reliable long-term survival of grafts derived from porcine expanded neural precursors in a rat model of PD, with maturation and integration into the host brain. This demonstrates that such xenografted cells may be able to recreate the damaged circuitry in PD although strategies for dopaminergic differentiation of the porcine neural precursor cell remain to be refined. PMID:16246328

  20. Neural Representations of Natural and Scrambled Movies Progressively Change from Rat Striate to Temporal Cortex.

    PubMed

    Vinken, Kasper; Van den Bergh, Gert; Vermaercke, Ben; Op de Beeck, Hans P

    2016-07-01

    In recent years, the rodent has come forward as a candidate model for investigating higher level visual abilities such as object vision. This view has been backed up substantially by evidence from behavioral studies that show rats can be trained to express visual object recognition and categorization capabilities. However, almost no studies have investigated the functional properties of rodent extrastriate visual cortex using stimuli that target object vision, leaving a gap compared with the primate literature. Therefore, we recorded single-neuron responses along a proposed ventral pathway in rat visual cortex to investigate hallmarks of primate neural object representations such as preference for intact versus scrambled stimuli and category-selectivity. We presented natural movies containing a rat or no rat as well as their phase-scrambled versions. Population analyses showed increased dissociation in representations of natural versus scrambled stimuli along the targeted stream, but without a clear preference for natural stimuli. Along the measured cortical hierarchy the neural response seemed to be driven increasingly by features that are not V1-like and destroyed by phase-scrambling. However, there was no evidence for category selectivity for the rat versus nonrat distinction. Together, these findings provide insights about differences and commonalities between rodent and primate visual cortex. PMID:27146315

  1. Neural Representations of Natural and Scrambled Movies Progressively Change from Rat Striate to Temporal Cortex

    PubMed Central

    Vinken, Kasper; Van den Bergh, Gert; Vermaercke, Ben; Op de Beeck, Hans P.

    2016-01-01

    In recent years, the rodent has come forward as a candidate model for investigating higher level visual abilities such as object vision. This view has been backed up substantially by evidence from behavioral studies that show rats can be trained to express visual object recognition and categorization capabilities. However, almost no studies have investigated the functional properties of rodent extrastriate visual cortex using stimuli that target object vision, leaving a gap compared with the primate literature. Therefore, we recorded single-neuron responses along a proposed ventral pathway in rat visual cortex to investigate hallmarks of primate neural object representations such as preference for intact versus scrambled stimuli and category-selectivity. We presented natural movies containing a rat or no rat as well as their phase-scrambled versions. Population analyses showed increased dissociation in representations of natural versus scrambled stimuli along the targeted stream, but without a clear preference for natural stimuli. Along the measured cortical hierarchy the neural response seemed to be driven increasingly by features that are not V1-like and destroyed by phase-scrambling. However, there was no evidence for category selectivity for the rat versus nonrat distinction. Together, these findings provide insights about differences and commonalities between rodent and primate visual cortex. PMID:27146315

  2. Neural Correlates of Animacy Attribution Include Neocerebellum in Healthy Adults.

    PubMed

    Jack, Allison; Pelphrey, Kevin A

    2015-11-01

    Recent work suggests that biological motion perception is supported by interactions between posterior superior temporal sulcus (pSTS) and regions of the posterior lobe of the cerebellum. However, insufficient attention has been given to cerebellar contributions to most other social cognitive functions, including ones that rely upon the use of biological motion cues for making mental inferences. Here, using adapted Heider and Simmel stimuli in a passive-viewing paradigm, we present functional magnetic resonance imaging evidence detailing cerebellar contributions to animacy attribution processes in healthy adults. We found robust cerebellar activity associated with viewing animate versus random movement in hemispheric lobule VII bilaterally as well as in vermal and paravermal lobule IX. Stronger activity in left Crus I and lobule VI was associated with a greater tendency to describe the stimuli in social-affective versus motion-related terms. Psychophysiological interaction analysis indicated preferential effective connectivity between right pSTS and left Crus II during the viewing of animate than random stimuli, controlling for individual variance in social attributions. These findings indicate that lobules VI, VII, and IX participate in social functions even when no active response is required. This cerebellar activity may also partially explain individual differences in animacy attribution. PMID:24981794

  3. Mechanically induced orientation of adult rat cardiac myocytes in vitro

    NASA Technical Reports Server (NTRS)

    Samuel, J.-L.; Vandenburgh, H. H.

    1990-01-01

    The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

  4. Microarray analysis of thyroid hormone-induced changes in mRNA expression in the adult rat brain.

    PubMed

    Haas, Michael J; Mreyoud, Amjad; Fishman, Miriam; Mooradian, Arshag D

    2004-07-15

    To determine which genes in the adult rat brain are regulated by thyroid hormone (TH), we used microarrays to examine the effect of hyperthyroidism on neuron-specific gene expression. Four-month-old male Fisher 344 rats were rendered hyperthyroid by intraperitoneal injection of 3,5,3'-L-triiodothyronine (T3, 15 microg/100 g body weight) for 10 consecutive days. To minimize interindividual variability, pooled cerebral tissue RNA from four-control and five-hyperthyroid rats was hybridized in duplicates to the Affymetrix (Santa Clara, CA) U34N rat neurobiology microarray, which contains probes for 1224 neural-specific genes. Changes in gene expression were considered significant only if they were observed in both pair-wise comparisons as well as by Northern blot analysis. Hyperthyroidism was associated with modest changes in the expression of only 11 genes. The expression of the phosphodiesterase Enpp2, myelin oligodendrocyte glycoprotein (Mog), microtubule-associated protein 2 (MAP2), growth hormone (GH), Ca(2+)/calmodulin-dependent protein kinase beta-subunit (Camk2b), neuron-specific protein PEP-19 (Pcp4), a sodium-dependent neurotransmitter, and the myelin-associated glycoprotein (S-MAG) was significantly increased. Three genes were suppressed by hyperthyroidism, including the activity and neurotransmitter-induced early genes-1 and -7 (ANIA-1 and ANIA-7) and the guanine nucleotide-binding protein one (Gnb1). The present study underscores the paucity of TH responsive genes in adult cerebral tissue. PMID:15234464

  5. Repeated Exposure of Adult Rats to Transient Oxidative Stress Induces Various Long-Lasting Alterations in Cognitive and Behavioral Functions

    PubMed Central

    Iguchi, Yoshio; Kosugi, Sakurako; Nishikawa, Hiromi; Lin, Ziqiao; Minabe, Yoshio; Toda, Shigenobu

    2014-01-01

    Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing) rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates. PMID:25489939

  6. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    PubMed

    Iguchi, Yoshio; Kosugi, Sakurako; Nishikawa, Hiromi; Lin, Ziqiao; Minabe, Yoshio; Toda, Shigenobu

    2014-01-01

    Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX) to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing) rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates. PMID:25489939

  7. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  8. Morphine Inhibited the Rat Neural Stem Cell Proliferation Rate by Increasing Neuro Steroid Genesis.

    PubMed

    Feizy, Navid; Nourazarian, Alireza; Rahbarghazi, Reza; Nozad Charoudeh, Hojjatollah; Abdyazdani, Nima; Montazersaheb, Soheila; Narimani, Mohamadreza

    2016-06-01

    Up to present, a large number of reports unveiled exacerbating effects of both long- and short-term administration of morphine, as a potent analgesic agent, on opium-addicted individuals and a plethora of cell kinetics, although contradictory effect of morphine on different cells have been introduced until yet. To address the potent modulatory effect of morphine on neural multipotent precursors with emphasis on endogenous sex-related neurosteroids biosynthesis, we primed the rat neural stem cells isolated from embryonic rat telencephalon to various concentrations of morphine including 10, 20, 50 and 100 µM alone or in combination with naloxone (100 µM) over period of 72 h. Flow cytometric Ki-67 expression and Annexin-V/PI based necrosis and apoptosis of exposed cells were evaluated. The total content of dihydrotestosterone and estradiol in cell supernatant was measured by ELISA. According on obtained data, both concentration- and time-dependent decrement of cell viability were orchestrated thorough down-regulation of ki-67 and simultaneous up-regulation of Annexin-V. On the other hand, the addition of naloxone (100 µM), as Mu opiate receptor antagonist, could blunt the morphine-induced adverse effects. It also well established that time-course exposure of rat neural stem cells with morphine potently could accelerate the endogenous dihydrotestosterone and estradiol biosynthesis. Interestingly, naloxone could consequently attenuate the enhanced neurosteroidogenesis time-dependently. It seems that our results discover a biochemical linkage between an accelerated synthesis of sex-related steroids and rat neural stem cells viability. PMID:26830291

  9. Neural processing associated with cognitive and affective Theory of Mind in adolescents and adults.

    PubMed

    Sebastian, Catherine L; Fontaine, Nathalie M G; Bird, Geoffrey; Blakemore, Sarah-Jayne; Brito, Stephane A De; McCrory, Eamon J P; Viding, Essi

    2012-01-01

    Theory of Mind (ToM) is the ability to attribute thoughts, intentions and beliefs to others. This involves component processes, including cognitive perspective taking (cognitive ToM) and understanding emotions (affective ToM). This study assessed the distinction and overlap of neural processes involved in these respective components, and also investigated their development between adolescence and adulthood. While data suggest that ToM develops between adolescence and adulthood, these populations have not been compared on cognitive and affective ToM domains. Using fMRI with 15 adolescent (aged 11-16 years) and 15 adult (aged 24-40 years) males, we assessed neural responses during cartoon vignettes requiring cognitive ToM, affective ToM or physical causality comprehension (control). An additional aim was to explore relationships between fMRI data and self-reported empathy. Both cognitive and affective ToM conditions were associated with neural responses in the classic ToM network across both groups, although only affective ToM recruited medial/ventromedial PFC (mPFC/vmPFC). Adolescents additionally activated vmPFC more than did adults during affective ToM. The specificity of the mPFC/vmPFC response during affective ToM supports evidence from lesion studies suggesting that vmPFC may integrate affective information during ToM. Furthermore, the differential neural response in vmPFC between adult and adolescent groups indicates developmental changes in affective ToM processing. PMID:21467048

  10. Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis.

    PubMed

    Zhang, Juan; Jiao, Jianwei

    2015-01-01

    The procedure of neurogenesis has made numerous achievements in the past decades, during which various molecular biomarkers have been emerging and have been broadly utilized for the investigation of embryonic and adult neural stem cell (NSC). Nevertheless, there is not a consistent and systematic illustration to depict the functional characteristics of the specific markers expressed in distinct cell types during the different stages of neurogenesis. Here we gathered and generalized a series of NSC biomarkers emerging during the procedures of embryonic and adult neural stem cell, which may be used to identify the subpopulation cells with distinguishing characters in different timeframes of neurogenesis. The identifications of cell patterns will provide applications to the detailed investigations of diverse developmental cell stages and the extents of cell differentiation, which will facilitate the tracing of cell time-course and fate determination of specific cell types and promote the further and literal discoveries of embryonic and adult neurogenesis. Meanwhile, via the utilization of comprehensive applications under the aiding of the systematic knowledge framework, researchers may broaden their insights into the derivation and establishment of novel technologies to analyze the more detailed process of embryogenesis and adult neurogenesis. PMID:26421301

  11. Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis

    PubMed Central

    Zhang, Juan; Jiao, Jianwei

    2015-01-01

    The procedure of neurogenesis has made numerous achievements in the past decades, during which various molecular biomarkers have been emerging and have been broadly utilized for the investigation of embryonic and adult neural stem cell (NSC). Nevertheless, there is not a consistent and systematic illustration to depict the functional characteristics of the specific markers expressed in distinct cell types during the different stages of neurogenesis. Here we gathered and generalized a series of NSC biomarkers emerging during the procedures of embryonic and adult neural stem cell, which may be used to identify the subpopulation cells with distinguishing characters in different timeframes of neurogenesis. The identifications of cell patterns will provide applications to the detailed investigations of diverse developmental cell stages and the extents of cell differentiation, which will facilitate the tracing of cell time-course and fate determination of specific cell types and promote the further and literal discoveries of embryonic and adult neurogenesis. Meanwhile, via the utilization of comprehensive applications under the aiding of the systematic knowledge framework, researchers may broaden their insights into the derivation and establishment of novel technologies to analyze the more detailed process of embryogenesis and adult neurogenesis. PMID:26421301

  12. Quiescent adult neural stem cells are exceptionally sensitive to cosmic radiation

    PubMed Central

    Encinas, Juan M.; Vazquez, Marcelo E.; Switzer, Robert C.; Chamberland, Dennis W.; Nick, Harry; Levine, Howard G.; Scarpa, Philip J.; Enikolopov, Grigori; Steindler, Dennis A.

    2012-01-01

    Generation of new neurons in the adult brain, a process that is likely to be essential for learning, memory, and mood regulation, is impaired by radiation. Therefore, radiation exposure might have not only such previously expected consequences as increased probability of developing cancer, but might also impair cognitive function and emotional stability. Radiation exposure is encountered in settings ranging from cancer therapy to space travel; evaluating the neurogenic risks of radiation requires identifying the at-risk populations of stem and progenitor cells in the adult brain. Here we have used a novel reporter mouse line to find that early neural progenitors are selectively affected by conditions simulating the space radiation environment. This is reflected both in a decrease in the number of these progenitors in the neurogenic regions and in an increase in the number of dying cells in these regions. Unexpectedly, we found that quiescent neural stem cells, rather than their rapidly dividing progeny, are most sensitive to radiation. Since these stem cells are responsible for adult neurogenesis, their death would have a profound impact on the production of new neurons in the irradiated adult brain. Our finding raises an important concern about cognitive and emotional risks associated with radiation exposure. PMID:18076878

  13. Frontal preparatory neural oscillations associated with cognitive control: A developmental study comparing young adults and adolescents.

    PubMed

    Hwang, Kai; Ghuman, Avniel S; Manoach, Dara S; Jones, Stephanie R; Luna, Beatriz

    2016-08-01

    Functional magnetic resonance imaging (fMRI) studies suggest that age-related changes in the frontal cortex may underlie developmental improvements in cognitive control. In the present study we used magnetoencephalography (MEG) to identify frontal oscillatory neurodynamics that support age-related improvements in cognitive control during adolescence. We characterized the differences in neural oscillations in adolescents and adults during the preparation to suppress a prepotent saccade (antisaccade trials-AS) compared to preparing to generate a more automatic saccade (prosaccade trials-PS). We found that for adults, AS were associated with increased beta-band (16-38Hz) power in the dorsal lateral prefrontal cortex (DLPFC), enhanced alpha- to low beta-band (10-18Hz) power in the frontal eye field (FEF) that predicted performance, and increased cross-frequency alpha-beta (10-26Hz) amplitude coupling between the DLPFC and the FEF. Developmental comparisons between adults and adolescents revealed similar engagement of DLPFC beta-band power but weaker FEF alpha-band power, and lower cross-frequency coupling between the DLPFC and the FEF in adolescents. These results suggest that lateral prefrontal neural activity associated with cognitive control is adult-like by adolescence; the development of cognitive control from adolescence to adulthood is instead associated with increases in frontal connectivity and strengthening of inhibition signaling for suppressing task-incompatible processes. PMID:27173759

  14. Medium-intensity acute exhaustive exercise induces neural cell apoptosis in the rat hippocampus.

    PubMed

    Li, Shanni; Liu, Jin; Yan, Hengmei

    2013-01-15

    The present study assessed the influence of medium-intensity (treadmill at a speed of 19.3 m/min until exhaustion) and high-intensity (treadmill at a speed of 26.8 m/min until exhaustion) acute exhaustive exercise on rat hippocampal neural cell apoptosis. TUNEL staining showed significantly increased neural cell apoptosis in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise, particularly the medium-intensity acute exhaustive exercise, when compared with the control. Immunohistochemistry showed significantly increased expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise. Additionally, the ratio of Bax to Bcl-2 increased in both exercise groups. In particular, the medium-intensity acute exhaustive exercise group had significantly higher Bax and Bcl-2 protein expression and a higher Bax/Bcl-2 ratio. These findings indicate that acute exhaustive exercise of different intensities can induce neural cell apoptosis in the hippocampus, and that medium-intensity acute exhaustive exercise results in greater damage when compared with high-intensity exercise. PMID:25206482

  15. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

    NASA Technical Reports Server (NTRS)

    Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

    1997-01-01

    Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

  16. TIN DISTRIBUTION IN ADULT RAT TISSUES AFTER EXPOSURE TO TRIMETHYLTIN AND TRIETHYLTIN

    EPA Science Inventory

    The time course of distribution of tin in the adult rat was determined in brain, liver kidney, heart, and blood following single ip administrations of trimethyltin hydroxide (TMT) and triethyltin bromide (TET). Adult Long-Evans rats were killed 1 hr, 4 hr, 12 hr, 24 hr, 5 days, 1...

  17. DERMAL PENETRATION OF [14C] CAPTAN IN YOUNG AND ADULT RATS

    EPA Science Inventory

    Dermal penetration of [14C] Captan was determined in young (33 day old) and adult (82 day old) female Fischer 344 rats by an in vivo method and two in vitro methods. ermal penetration in vivo at 72 hours was about 9% of the dose in both young and adult rats. o significant differe...

  18. 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

  19. Decline of taste sensitivity in protein deficient adult rats.

    PubMed

    Ohara, I; Tabuchi, R; Kimura, M; Itokawa, Y

    1995-05-01

    The influence of dietary protein levels on taste sensitivity was studied in adult rats. Low protein diets of 0.0, 2.5, or 5.0% purified egg protein (PEP) were fed to animals for 28 days. Two bottle choice preference tests between aqueous solutions of either 2, 9, 17, or 86 mM sodium chloride and deionized water were conducted in an ascending order on days 14, 16, 18, and 20. Urine samples were collected for zinc and creatinine analysis. Blood samples were also collected for measuring serum zinc and creatinine concentrations. Scanning electron microscopy was performed to observe rats' tongue epithelia. Protein free diet group showed significantly lower taste sensitivity and renal reabsorption rate than other protein containing diet groups, while serum zinc and creatinine concentrations, and creatinine clearance were not affected by dietary protein level. Degeneration of filiform papillae and imperforation of taste pore of fungiform papillae were observed in protein free diet group. This experiment implies at least 2.5% dietary protein is required to manifest normal taste function in the adult. PMID:7610145

  20. Prediction of Clinical Deterioration in Hospitalized Adult Patients with Hematologic Malignancies Using a Neural Network Model

    PubMed Central

    Hu, Scott B.; Wong, Deborah J. L.; Correa, Aditi; Li, Ning; Deng, Jane C.

    2016-01-01

    Introduction Clinical deterioration (ICU transfer and cardiac arrest) occurs during approximately 5–10% of hospital admissions. Existing prediction models have a high false positive rate, leading to multiple false alarms and alarm fatigue. We used routine vital signs and laboratory values obtained from the electronic medical record (EMR) along with a machine learning algorithm called a neural network to develop a prediction model that would increase the predictive accuracy and decrease false alarm rates. Design Retrospective cohort study. Setting The hematologic malignancy unit in an academic medical center in the United States. Patient Population Adult patients admitted to the hematologic malignancy unit from 2009 to 2010. Intervention None. Measurements and Main Results Vital signs and laboratory values were obtained from the electronic medical record system and then used as predictors (features). A neural network was used to build a model to predict clinical deterioration events (ICU transfer and cardiac arrest). The performance of the neural network model was compared to the VitalPac Early Warning Score (ViEWS). Five hundred sixty five consecutive total admissions were available with 43 admissions resulting in clinical deterioration. Using simulation, the neural network outperformed the ViEWS model with a positive predictive value of 82% compared to 24%, respectively. Conclusion We developed and tested a neural network-based prediction model for clinical deterioration in patients hospitalized in the hematologic malignancy unit. Our neural network model outperformed an existing model, substantially increasing the positive predictive value, allowing the clinician to be confident in the alarm raised. This system can be readily implemented in a real-time fashion in existing EMR systems. PMID:27532679

  1. Adult neural stem cells in distinct microdomains generate previously unknown interneuron types

    PubMed Central

    Merkle, Florian T.; Fuentealba, Luis C.; Sanders, Timothy A.; Magno, Lorenza; Kessaris, Nicoletta; Alvarez-Buylla, Arturo

    2014-01-01

    Throughout life, neural stem cells (NSCs) in different domains of the ventricular-subventricular zone (V-SVZ) of the adult rodent brain generate several subtypes of interneurons that regulate the function of the olfactory bulb (OB). The full extent of diversity among adult NSCs and their progeny is not known. Here, we report the generation of at least four previously unknown OB interneuron subtypes that are produced in finely patterned progenitor domains in the anterior ventral V-SVZ of both the neonatal and adult brain. Progenitors of these novel interneurons are responsive to sonic hedgehog (SHH) and are organized into microdomains that correlate with the expression domains of the Nkx6.2 and Zic family of transcription factors. This work reveals an unexpected degree of complexity in the specification and patterning of NSCs in the postnatal mouse brain. PMID:24362763

  2. Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve

    PubMed Central

    Lang, Hainan; Xing, Yazhi; Brown, LaShardai N.; Samuvel, Devadoss J.; Panganiban, Clarisse H.; Havens, Luke T.; Balasubramanian, Sundaravadivel; Wegner, Michael; Krug, Edward L.; Barth, Jeremy L.

    2015-01-01

    The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration. PMID:26307538

  3. Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

    PubMed

    Aly, Hamdy A A; Mansour, Ahmed M; Hassan, Memy H; Abd-Ellah, Mohamed F

    2016-08-01

    The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016. PMID:25533183

  4. Beta-cyfluthrin induced neurobehavioral impairments in adult rats.

    PubMed

    Syed, Farah; Chandravanshi, Lalit P; Khanna, Vinay K; Soni, Inderpal

    2016-01-01

    Beta-cyfluthrin (CYF) is a commonly used synthetic pyrethroid having both agricultural and domestic applications. The present study aimed to evaluate the neurobehavioural effects of beta-cyfluthrin in adult rats administered at doses 25 mg/kg body weight/day and 12.5 mg/kg body weight/day for a period of 30 days. Motor coordination and spatial memory were found to be impaired by beta-cyfluthrin. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), epinephrine (EPN), and serotonin (5-HT) decreased in frontal cortex, corpus striatum and hippocampus of treated rats. At the same time, significantly elevated levels of homovanillic acid (HVA) and nor-epinephrine (NE) were measured. Beta-cyfluthrin inhibited the activity of acetylcholinesterase (AChE) in all the regions of the brain. Hippocampal choline acetyltransferase (ChAT) expression was reduced 3.1 and 4.7 fold by the two doses respectively. Impairment of the antioxidant defense system, evident by decrease in the levels of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) was seen in the treated rats. The neurochemical alterations manifested were more pronounced in the high dose group as the effects persisted even after withdrawal of exposure. PMID:26604153

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

    PubMed

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

    2016-04-01

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

  6. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

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

    2009-01-01

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

  7. Neural mechanisms of sensitivity to peer information in young adult cannabis users.

    PubMed

    Gilman, Jodi M; Schuster, Randi M; Curran, Max T; Calderon, Vanessa; van der Kouwe, Andre; Evins, A Eden

    2016-08-01

    Though social influence is a critical factor in the initiation and maintenance of marijuana use, the neural correlates of influence in those who use marijuana are unknown. In this study, marijuana-using young adults (MJ; n = 20) and controls (CON; n = 23) performed a decision-making task in which they made a perceptual choice after viewing the choices of unknown peers via photographs, while they underwent functional magnetic resonance imaging scans. The MJ and CON groups did not show differences in the overall number of choices that agreed with versus opposed group influence, but only the MJ group showed reaction time slowing when deciding against group choices. Longer reaction times were associated with greater activation of frontal regions. The MJ goup, compared to CON, showed significantly greater activation in the caudate when presented with peer information. Across groups, caudate activation was associated with self-reported susceptibility to influence. These findings indicate that young adults who use MJ may exhibit increased effort when confronted with opposing peer influence, as well as exhibit greater responsivity of the caudate to social information. These results not only better define the neural basis of social decisions, but also suggest that marijuana use is associated with exaggerated neural activity during decision making that involves social information. PMID:27068178

  8. Adult human neural stem cell therapeutics: Current developmental status and prospect

    PubMed Central

    Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as cell therapeutics for neurological disease. Compared with other types of stem cells, aNSCs have clinical advantages, such as limited proliferation, inborn differentiation potential into functional neural cells, and no ethical issues. In spite of the merits of aNSCs, difficulties in the isolation from the normal brain, and in the in vitro expansion, have blocked preclinical and clinical study using aNSCs. However, several groups have recently developed novel techniques to isolate and expand aNSCs from normal adult brains, and showed successful applications of aNSCs to neurological diseases. With new technologies for aNSCs and their clinical strengths, previous hurdles in stem cell therapies for neurological diseases could be overcome, to realize clinically efficacious regenerative stem cell therapeutics. PMID:25621112

  9. Impaired Survival of Neural Progenitor Cells in Dentate Gyrus of Adult Mice Lacking FMRP

    PubMed Central

    Lazarov, Orly; Demars, Michael P.; Zhao, Kai Da Tommy; Ali, Haroon M.; Grauzas, Vanessa; Kney, Adam; Larson, John

    2011-01-01

    Fragile X syndrome (FXS) is the most common form of inherited intellectual disability in humans. Individuals affected with the disorder exhibit a deficiency of the fragile X mental retardation protein (FMRP), due to transcriptional silencing of the Fmr1 gene. It is widely accepted that learning deficits in FXS result from impaired synaptic function and/or plasticity in the brain. Interestingly, recent evidence suggests that conditional knockout of Fmr1 in neural progenitor cells in mice impairs hippocampal neurogenesis, which in turn contributes to learning impairments. To examine the nature of the neurogenic impairments and determine whether they impact the morphology of the dentate gyrus, we assessed the extent of neural progenitor cell proliferation, survival, and differentiation in older adult Fmr1 knockout mice. Here we show that the number of fast- proliferating cells in the subgranule layer of the dentate gyrus, as well as the subsequent survival of these cells, are dramatically reduced in Fmr1 knockout mice. In addition, the number of mature neurons in the granule layer of the dentate gyrus of these mice is significantly smaller than in WT littermate controls, suggesting that impaired proliferation and survival of neural progenitor cells compromises the structure of the dentate gyrus. Impaired adult neurogenesis may underlie, at least in part, the learning deficits that characterize fragile X syndrome. PMID:22128095

  10. Catalog of gene expression in adult neural stem cells and their in vivo microenvironment

    SciTech Connect

    Williams, Cecilia; Wirta, Valtteri; Meletis, Konstantinos; Wikstroem, Lilian; Carlsson, Leif; Frisen, Jonas; Lundeberg, Joakim . E-mail: joakim.lundeberg@biotech.kth.se

    2006-06-10

    Stem cells generally reside in a stem cell microenvironment, where cues for self-renewal and differentiation are present. However, the genetic program underlying stem cell proliferation and multipotency is poorly understood. Transcriptome analysis of stem cells and their in vivo microenvironment is one way of uncovering the unique stemness properties and provides a framework for the elucidation of stem cell function. Here, we characterize the gene expression profile of the in vivo neural stem cell microenvironment in the lateral ventricle wall of adult mouse brain and of in vitro proliferating neural stem cells. We have also analyzed an Lhx2-expressing hematopoietic-stem-cell-like cell line in order to define the transcriptome of a well-characterized and pure cell population with stem cell characteristics. We report the generation, assembly and annotation of 50,792 high-quality 5'-end expressed sequence tag sequences. We further describe a shared expression of 1065 transcripts by all three stem cell libraries and a large overlap with previously published gene expression signatures for neural stem/progenitor cells and other multipotent stem cells. The sequences and cDNA clones obtained within this framework provide a comprehensive resource for the analysis of genes in adult stem cells that can accelerate future stem cell research.

  11. Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation

    PubMed Central

    Fatt, Michael; Hsu, Karolynn; He, Ling; Wondisford, Fredric; Miller, Freda D.; Kaplan, David R.; Wang, Jing

    2015-01-01

    Summary The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved diabetes drug, promotes proliferation, self-renewal, and differentiation of adult neural precursors (NPCs). Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Thus, metformin represents an optimal candidate neuro-regenerative agent that is capable of not only expanding the adult NPC population but also subsequently driving them toward neuronal differentiation by activating two distinct molecular pathways. PMID:26677765

  12. Neural regulation of the kidney function in rats with cisplatin induced renal failure

    PubMed Central

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

    Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

  13. Behavioral outcome measures used for human neural stem cell transplantation in rat stroke models

    PubMed Central

    Jensen, Matthew B.; Han, Dong Y.; Sawaf, Abdullah Al; Krishnaney-Davison, Rajeev

    2011-01-01

    Stroke is a leading cause of death and disability, leading to the development of various stroke models to test new treatments, most commonly in the rat. Human stroke trials focus on disability, related primarily to neurological deficits. To better model the clinical application of these treatments, many behavioral tests have been developed using the rat stroke model. We performed a systematic review of all the behavioral outcome measures used in published studies of human neural stem cell transplantation in rat stroke models. The reviewed tests include motor, sensory, cognitive, activity, and combination tests. For each test, we give a brief description, trace the origin of the test, and discuss test performance in the reviewed studies. We conclude that while many behavioral tests are available for this purpose, there does not appear to be consensus on an optimal testing strategy. PMID:22053257

  14. Residual Neural Processing of Musical Sound Features in Adult Cochlear Implant Users

    PubMed Central

    Timm, Lydia; Vuust, Peter; Brattico, Elvira; Agrawal, Deepashri; Debener, Stefan; Büchner, Andreas; Dengler, Reinhard; Wittfoth, Matthias

    2014-01-01

    Auditory processing in general and music perception in particular are hampered in adult cochlear implant (CI) users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioral study comparing adult CI users with normal-hearing age-matched controls (NH controls). We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20 min. The presentation of stimuli did not require the participants’ attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timber. No other group differences in MMN parameters were found to changes in intensity and saxophone timber. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients’ age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioral and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood. Highlights: -Automatic brain responses to musical feature changes

  15. Iodine-125-labeled triiodothyronine in rat brain: evidence for localization in discrete neural systems

    SciTech Connect

    Dratman, M.B.; Futaesaku, Y.; Crutchfield, F.L.; Berman, N.; Payne, B.; Sar, M.; Stumpf, W.E.

    1982-01-15

    Autoradiograms prepared from adult rat brains demonstrate that nerve cells and neuropil in different brain regions selectively concentrate and retain intravenously administered triiodothyronine, by mechanisms susceptible to saturation with excess triiodothyronine. A neuroregulatory role for thyroid hormones, strongly supported by the observations, may account for their marked effects on behavior and the activity of the autonomic nervous system.

  16. Contrasting regional Fos expression in adolescent and young adult rats following acute administration of the antidepressant paroxetine.

    PubMed

    Karanges, Emily A; Ramos, Linnet; Dampney, Bruno; Suraev, Anastasia S; Li, Kong M; McGregor, Iain S; Hunt, Glenn E

    2016-03-01

    Adolescents and adults may respond differently to antidepressants, with poorer efficacy and greater probability of adverse effects in adolescents. The mechanisms underlying this differential response are largely unknown, but likely relate to an interaction between the neural effects of antidepressants and brain development. We used Fos immunohistochemistry to examine regional differences in adolescent (postnatal day (PND) 28) and young adult (PND 56) male, Wistar rats given a single injection of the selective serotonin reuptake inhibitor paroxetine (10mg/kg). Paroxetine induced widespread Fos expression in both adolescent and young adult rats. Commonly affected areas include the bed nucleus of the stria terminalis (dorsolateral), medial preoptic area, paraventricular hypothalamic and thalamic nuclei and central nucleus of the amygdala. Fos expression was generally lower in adolescents with significantly greater Fos expression observed in young adults in the prelimbic cortex, supraoptic nucleus, basolateral amygdala, lateral parabrachial and Kölliker-Fuse nuclei. However, a small subset of regions showed greater adolescent Fos expression including the nucleus accumbens shell, lateral habenula and dorsal raphe. Paroxetine increased plasma corticosterone concentrations in young adults, but not adolescents. Plasma paroxetine levels were not significantly different between the age groups. These results indicate a different c-Fos signature of acute paroxetine in adolescent rats, with greater activation in key mesolimbic and serotonergic regions, but a more subdued cortical, brainstem and hypothalamic response. This suggests that the atypical response of adolescents to paroxetine may be related to a blunted neuroendocrine response, combined with insufficient top-down regulation of limbic regions involved in reward and impulsivity. PMID:26876759

  17. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages.

    PubMed

    Seaberg, Raewyn M; Smukler, Simon R; Kieffer, Timothy J; Enikolopov, Grigori; Asghar, Zeenat; Wheeler, Michael B; Korbutt, Gregory; van der Kooy, Derek

    2004-09-01

    The clonal isolation of putative adult pancreatic precursors has been an elusive goal of researchers seeking to develop cell replacement strategies for diabetes. We report the clonal identification of multipotent precursor cells from the adult mouse pancreas. The application of a serum-free, colony-forming assay to pancreatic cells enabled the identification of precursors from pancreatic islet and ductal populations. These cells proliferate in vitro to form clonal colonies that coexpress neural and pancreatic precursor markers. Upon differentiation, individual clonal colonies produce distinct populations of neurons and glial cells, pancreatic endocrine beta-, alpha- and delta-cells, and pancreatic exocrine and stellate cells. Moreover, the newly generated beta-like cells demonstrate glucose-dependent Ca(2+) responsiveness and insulin release. Pancreas colonies do not express markers of embryonic stem cells, nor genes suggestive of mesodermal or neural crest origins. These cells represent a previously unidentified adult intrinsic pancreatic precursor population and are a promising candidate for cell-based therapeutic strategies. PMID:15322557

  18. Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

    PubMed

    Kim, Joo Yeon; Choi, Kyuhyun; Shaker, Mohammed R; Lee, Ju-Hyun; Lee, Boram; Lee, Eunsoo; Park, Jae-Yong; Lim, Mi-Sun; Park, Chang-Hwan; Shin, Ki Soon; Kim, Hyun; Geum, Dongho; Sun, Woong

    2016-04-01

    Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy. Stem Cells 2016;34:888-901. PMID:26701067

  19. Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse.

    PubMed

    Furube, Eriko; Morita, Mitsuhiro; Miyata, Seiji

    2015-11-01

    Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions. PMID:25994374

  20. Isolation of Novel Multipotent Neural Crest-Derived Stem Cells from Adult Human Inferior Turbinate

    PubMed Central

    Hauser, Stefan; Widera, Darius; Qunneis, Firas; Müller, Janine; Zander, Christin; Greiner, Johannes; Strauss, Christina; Lüningschrör, Patrick; Heimann, Peter; Schwarze, Hartmut; Ebmeyer, Jörg; Sudhoff, Holger; Araúzo-Bravo, Marcos J.; Greber, Boris; Zaehres, Holm; Schöler, Hans; Kaltschmidt, Christian

    2012-01-01

    Adult human neural crest-derived stem cells (NCSCs) are of extraordinary high plasticity and promising candidates for the use in regenerative medicine. Here we describe for the first time a novel neural crest-derived stem cell population within the respiratory epithelium of human adult inferior turbinate. In contrast to superior and middle turbinates, high amounts of source material could be isolated from human inferior turbinates. Using minimally-invasive surgery methods isolation is efficient even in older patients. Within their endogenous niche, inferior turbinate stem cells (ITSCs) expressed high levels of nestin, p75NTR, and S100. Immunoelectron microscopy using anti-p75 antibodies displayed that ITSCs are of glial origin and closely related to nonmyelinating Schwann cells. Cultivated ITSCs were positive for nestin and S100 and the neural crest markers Slug and SOX10. Whole genome microarray analysis showed pronounced differences to human ES cells in respect to pluripotency markers OCT4, SOX2, LIN28, and NANOG, whereas expression of WDR5, KLF4, and c-MYC was nearly similar. ITSCs were able to differentiate into cells with neuro-ectodermal and mesodermal phenotype. Additionally ITSCs are able to survive and perform neural crest typical chain migration in vivo when transplanted into chicken embryos. However ITSCs do not form teratomas in severe combined immunodeficient mice. Finally, we developed a separation strategy based on magnetic cell sorting of p75NTR positive ITSCs that formed larger neurospheres and proliferated faster than p75NTR negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy. PMID:22128806

  1. 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

  2. Inhibition of Adult Rat Retinal Ganglion Cells by D1-type Dopamine Receptor Activation

    PubMed Central

    Hayashida, Yuki; Rodríguez, Carolina Varela; Ogata, Genki; Partida, Gloria J.; Oi, Hanako; Stradleigh, Tyler W.; Lee, Sherwin C.; Colado, Anselmo Felipe; Ishida, Andrew T.

    2011-01-01

    The spike output of neural pathways can be regulated by modulating output neuron excitability and/or their synaptic inputs. Dopaminergic interneurons synapse onto cells that route signals to mammalian retinal ganglion cells, but it is unknown whether dopamine can activate receptors in these ganglion cells and, if it does, how this affects their excitability. Here, we show D1a-receptor-like immunoreactivity in ganglion cells identified in adult rats by retrogradely transported dextran, and that dopamine, D1-type receptor agonists, and cAMP analogs inhibit spiking in ganglion cells dissociated from adult rats. These ligands curtailed repetitive spiking during constant current injections, and reduced the number and rate of rise of spikes elicited by fluctuating current injections without significantly altering the timing of the remaining spikes. Consistent with mediation by D1-type receptors, SCH-23390 reversed the effects of dopamine on spikes. Contrary to a recent report, spike inhibition by dopamine was not precluded by blocking Ih. Consistent with the reduced rate of spike rise, dopamine reduced voltage-gated Na+ current (INa) amplitude and tetrodotoxin, at doses that reduced INa as moderately as dopamine, also inhibited spiking. These results provide the first direct evidence that D1-type dopamine receptor activation can alter mammalian retinal ganglion cell excitability, and demonstrate that dopamine can modulate spikes in these cells by a mechanism different from the pre- and postsynaptic means proposed by previous studies. To our knowledge, our results also provide the first evidence that dopamine receptor activation can reduce excitability without altering the temporal precision of spike firing. PMID:19940196

  3. Expression of Lymphatic Markers in the Adult Rat Spinal Cord

    PubMed Central

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A.; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  4. Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow.

    PubMed

    Glejzer, A; Laudet, E; Leprince, P; Hennuy, B; Poulet, C; Shakhova, O; Sommer, L; Rogister, B; Wislet-Gendebien, S

    2011-06-01

    Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. PMID:20976520

  5. Distinct neural correlates of emotional and cognitive empathy in older adults

    PubMed Central

    Moore, Raeanne C.; Dev, Sheena I.; Jeste, Dilip V.; Dziobek, Isabel; Eyler, Lisa T.

    2014-01-01

    Empathy is thought to be a mechanism underlying prosocial behavior across the lifespan, yet little is known about how levels of empathy relate to individual differences in brain functioning among older adults. In this exploratory study, we examined the neural correlates of affective and cognitive empathy in older adults. Thirty older adults (M=79 years) underwent fMRI scanning and neuropsychological testing and completed a test of affective and cognitive empathy. Brain response during processing of cognitive and emotional stimuli was measured by fMRI in a priori and task-related regions and was correlated with levels of empathy. Older adults with higher levels of affective empathy showed more deactivation in the amygdala and insula during a working memory task, whereas those with higher cognitive empathy showed greater insula activation during a response inhibition task. Our preliminary findings suggest that brain systems linked to emotional and social processing respond differently among older adults with more or less affective and cognitive empathy. That these relationships can be seen both during affective and non-emotional tasks of “cold” cognitive abilities suggests that empathy may impact social behavior through both emotional and cognitive mechanisms. PMID:25770039

  6. Distinct neural correlates of emotional and cognitive empathy in older adults.

    PubMed

    Moore, Raeanne C; Dev, Sheena I; Jeste, Dilip V; Dziobek, Isabel; Eyler, Lisa T

    2015-04-30

    Empathy is thought to be a mechanism underlying prosocial behavior across the lifespan, yet little is known about how levels of empathy relate to individual differences in brain functioning among older adults. In this exploratory study, we examined the neural correlates of affective and cognitive empathy in older adults. Thirty older adults (M=79 years) underwent fMRI scanning and neuropsychological testing and completed a test of affective and cognitive empathy. Brain response during processing of cognitive and emotional stimuli was measured by fMRI in a priori and task-related regions and was correlated with levels of empathy. Older adults with higher levels of affective empathy showed more deactivation in the amygdala and insula during a working memory task, whereas those with higher cognitive empathy showed greater insula activation during a response inhibition task. Our preliminary findings suggest that brain systems linked to emotional and social processing respond differently among older adults with more or less affective and cognitive empathy. That these relationships can be seen both during affective and non-emotional tasks of "cold" cognitive abilities suggests that empathy may impact social behavior through both emotional and cognitive mechanisms. PMID:25770039

  7. Action Prediction in Younger versus Older Adults: Neural Correlates of Motor Familiarity

    PubMed Central

    Diersch, Nadine; Mueller, Karsten; Cross, Emily S.; Stadler, Waltraud; Rieger, Martina; Schütz-Bosbach, Simone

    2013-01-01

    Generating predictions during action observation is essential for efficient navigation through our social environment. With age, the sensitivity in action prediction declines. In younger adults, the action observation network (AON), consisting of premotor, parietal and occipitotemporal cortices, has been implicated in transforming executed and observed actions into a common code. Much less is known about age-related changes in the neural representation of observed actions. Using fMRI, the present study measured brain activity in younger and older adults during the prediction of temporarily occluded actions (figure skating elements and simple movement exercises). All participants were highly familiar with the movement exercises whereas only some participants were experienced figure skaters. With respect to the AON, the results confirm that this network was preferentially engaged for the more familiar movement exercises. Compared to younger adults, older adults recruited visual regions to perform the task and, additionally, the hippocampus and caudate when the observed actions were familiar to them. Thus, instead of effectively exploiting the sensorimotor matching properties of the AON, older adults seemed to rely predominantly on the visual dynamics of the observed actions to perform the task. Our data further suggest that the caudate played an important role during the prediction of the less familiar figure skating elements in better-performing groups. Together, these findings show that action prediction engages a distributed network in the brain, which is modulated by the content of the observed actions and the age and experience of the observer. PMID:23704980

  8. Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells

    PubMed Central

    Smrt, Richard D.; Johnson, Eric B.; Li, Xuekun; Pfeiffer, Rebecca L.; Szulwach, Keith E.; Duan, Ranhui; Barkho, Basam Z.; Li, Wendi; Liu, Changmei; Jin, Peng; Zhao, Xinyu

    2010-01-01

    Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3β. Dysregulation of GSK3β led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis. PMID:20386739

  9. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

    NASA Astrophysics Data System (ADS)

    Ooto, Sotaro; Akagi, Tadamichi; Kageyama, Ryoichiro; Akita, Joe; Mandai, Michiko; Honda, Yoshihito; Takahashi, Masayo

    2004-09-01

    It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.

  10. Combined MSC-Secreted Factors and Neural Stem Cell Transplantation Promote Functional Recovery of PD Rats.

    PubMed

    Yao, Yuan; Huang, Chen; Gu, Ping; Wen, Tieqiao

    2016-01-01

    Stem cell transplantation has enormous potential for the treatment of neurodegenerative disorders like Parkinson's disease (PD). Mesenchymal stem cells (MSCs) have attracted much attention because they can secrete a wide variety of cellular factors that promote cell growth. In this study, we prepared a conditioned medium (CM) using lyophilized MSC culture medium that contained the secretome of MSCs and applied this CM to the culture of neural stem cells (CM-NSCs) for the transplantation of PD model rats. Quantitative real-time PCR, Western blot, and immunocytochemistry were used to identify cell differentiation and expression of dopaminergic neuron-specific genes in vitro. Behavioral tests including rotational behavior and MWM training tests were also performed to assess the recovery. Our results indicated that combined treatment of CM and neural stem cell transplantation can significantly reduce apomorphine-induced rotational asymmetry and improve spatial learning ability. The CM-NSCs were able to differentiate into dopaminergic neurons in the ventral tegmental area (VTA) and medial forebrain bundle (MFB), and migrated around the lesion site. They showed a higher activity than untreated NSCs in cell survival, migration, and behavior improvement in the dopa-deficit rat model. These findings suggest that the neural stem cells treated with conditioned medium possess a great potential as a graft candidate for the treatment of Parkinson's disease. PMID:26607204

  11. Long-term, stable differentiation of human embryonic stem cell-derived neural precursors grafted into the adult mammalian neostriatum.

    PubMed

    Nasonkin, Igor; Mahairaki, Vasiliki; Xu, Leyan; Hatfield, Glen; Cummings, Brian J; Eberhart, Charles; Ryugo, David K; Maric, Dragan; Bar, Eli; Koliatsos, Vassilis E

    2009-10-01

    Stem cell grafts have been advocated as experimental treatments for neurological diseases by virtue of their ability to offer trophic support for injured neurons and, theoretically, to replace dead neurons. Human embryonic stem cells (HESCs) are a rich source of neural precursors (NPs) for grafting, but have been questioned for their tendency to form tumors. Here we studied the ability of HESC-derived NP grafts optimized for cell number and differentiation stage prior to transplantation, to survive and stably differentiate and integrate in the basal forebrain (neostriatum) of young adult nude rats over long periods of time (6 months). NPs were derived from adherent monolayer cultures of HESCs exposed to noggin. After transplantation, NPs showed a drastic reduction in mitotic activity and an avid differentiation into neurons that projected via major white matter tracts to a variety of forebrain targets. A third of NP-derived neurons expressed the basal forebrain-neostriatal marker dopamine-regulated and cyclic AMP-regulated phosphoprotein. Graft-derived neurons formed mature synapses with host postsynaptic structures, including dendrite shafts and spines. NPs inoculated in white matter tracts showed a tendency toward glial (primarily astrocytic) differentiation, whereas NPs inoculated in the ventricular epithelium persisted as nestin(+) precursors. Our findings demonstrate the long-term ability of noggin-derived human NPs to structurally integrate tumor-free into the mature mammalian forebrain, while maintaining some cell fate plasticity that is strongly influenced by particular central nervous system (CNS) niches. PMID:19609935

  12. Long-Term, Stable Differentiation Of Human Embryonic Stem Cell-Derived Neural Precursors Grafted Into The Adult Mammalian Neostriatum

    PubMed Central

    Nasonkin, I.; Mahairaki, V.; Xu, L.; Hatfield, G.; Cummings, B.J.; Eberhart, C.; Ryugo, D.; Maric, D.; Bar, E.; Koliatsos, V.E.

    2010-01-01

    Stem-cell grafts have been advocated as experimental treatments for neurological diseases by virtue of their ability to offer trophic support for injured neurons and, theoretically, to replace dead neurons. Human embryonic stem cells (HESCs) are a rich source of neural precursors (NPs) for grafting, but have been questioned for their tendency to form tumors. Here we studied the ability of HESC-derived NP grafts optimized for cell number and differentiation stage prior to transplantation, to survive and stably differentiate and integrate in the basal forebrain (neostriatum) of young adult nude rats over long periods of time (6 months). NPs were derived from adherent monolayer cultures of HESCs exposed to noggin. After transplantation, NPs showed a drastic reduction in mitotic activity and an avid differentiation into neurons that projected via major white matter tracts to a variety of forebrain targets. A third of NP-derived neurons expressed the basal forebrain-neostriatal marker Dopamine- and cyclic AMP-Regulated Phosphoprotein. Graft-derived neurons formed mature synapses with host post-synaptic structures, including dendrite shafts and spines. NPs inoculated in white matter tracts showed a tendency towards glial (primarily astrocytic) differentiation, whereas NPs inoculated in the ventricular epithelium persisted as nestin (+) precursors. Our findings demonstrate the long-term ability of noggin-derived human NPs to structurally integrate tumor-free into the mature mammalian forebrain, while maintaining some cell fate plasticity that is strongly influenced by particular CNS niches. PMID:19609935

  13. Polygonal networks, "geodomes", of adult rat hepatocytes in primary culture.

    PubMed

    Mochizuki, Y; Furukawa, K; Mitaka, T; Yokoi, T; Kodama, T

    1988-01-01

    Polygonal networks, "geodomes", in cultured hepatocytes of adult rats were examined by both light and electron microscopy. On light microscopical examinations of specimens stained with Coomassie blue after the treatment with Triton X-100, the networks were detected 5 days after culture, which consisted of triangles arranged mainly in hexagonal patterns. They surrounded main cell body, looking like a headband, or were occasionally situated over nuclei, looking like a geodesic dome. Scanning electron microscopical observations after Triton treatment revealed that these structures were located underneath surface membrane. Transmission electron microscopical investigations revealed that the connecting fibers of networks consisted of microfilaments which radiated in a compact bundle from electron-dense vertices. PMID:3396075

  14. Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

    PubMed

    Krause, A; Nowak, Z; Srbu, R; Bell, H J

    2016-10-01

    In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID:27378495

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

    PubMed

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

    2015-05-15

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

  16. Controlling neural stem cell division within the adult subventricular zone: an APPealing job.

    PubMed

    Conti, Luciano; Cattaneo, Elena

    2005-02-01

    For years, scientists investigating amyloid precursor protein (APP) have focused on its pathogenetic role in the brains of Alzheimer's disease patients. Now, a study by Caille et al. adds new sites of action and new physiological functions for APP. They show that there are binding sites for secreted N-terminal nonamyloidogenic APP (sAPP) on epidermal growth factor (EGF)-responsive neural stem cells in the subventricular zone of the adult brain, where sAPP acts as an EGF cofactor to stimulate proliferation of these cells. This result opens the hypothesis that changes in the levels of sAPP could influence activity of the neurogenic regions of the adult brain in normal and pathological conditions. PMID:15667924

  17. The ventral hippocampus is the embryonic origin for adult neural stem cells in the dentate gyrus

    PubMed Central

    Li, Guangnan; Fang, Li; Fernández, Gloria; Pleasure, Samuel J.

    2013-01-01

    SUMMARY Adult neurogenesis represents a unique form of plasticity in the dentate gyrus requiring the presence of long-lived neural stem cells (LL-NSCs). However, the embryonic origin of these LL-NSCs remains unclear. The prevailing model assumes that the dentate neuroepithelium throughout the longitudinal axis of the hippocampus generates both the LL-NSCs and embryonically produced granule neurons. Here we show that the NSCs initially originate from the ventral hippocampus during late gestation and then relocate into the dorsal hippocampus. The descendants of these cells are the source for the LL-NSCs in the subgranular zone (SGZ). Furthermore, we show that the origin of these cells and their maintenance in the dentate are controlled by distinct sources of Sonic Hedgehog (Shh). The revelation of the complexity of both the embryonic origin of hippocampal LL-NSCs and the sources of Shh has important implications for the functions of LL-NSCs in the adult hippocampus. PMID:23643936

  18. Neural Correlates of Birth: Labor Contractions Induce C-Fos Expression In Newborn Rat Brain

    NASA Technical Reports Server (NTRS)

    Ronca, A. E.; Daly, M. E.; Baer, L. A.; Hills, E. M.; Conway, G.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    At birth, the newborn mammal must make rapid adaptations to the extrauterine environment to survive. We have previously shown that labor contractions augment the appearance of adaptive responses at birth, viz., postpartum breathing and the onset of suckling. Since neuronal activity has been shown to upregulate the activity of immediate early genes (IEGs) in the brain, we analyzed the neural distribution of c-Fos protein expression in newborn rats using immunohistochemistry. Previous studies have reported a burst of c-Fos mRNA expression in mouse and rat brain at birth however relationships to labor and delivery have not been examined. In the present study, we exposed near-term rat fetuses to elements of the vaginal birth process: 1) Simulated labor contractions. 2) Postpartum cooling (22 deg C). 3) Umbilical cord occlusion. and 4) Stroking to mimic postpartum licking by the dam. Cardinally delivered newborns (VG) were compared with those delivered by cesarean section following either prenatal exposure to compressions (C) [simulated labor contractions], or no compressions (NC) [no labor contractions]. Similar patterns of c-fos activation were observed throughout hypothalamic and thalamic nuclei, hippocampus and cerebral cortex in VG and C newborns that were not apparent in NC newborns. Our results indicate that labor contractions play a role in the induction of widespread neural activation in the newborn brain.

  19. Dietary essential fatty acids change the fatty acid profile of rat neural mitochondria over time.

    PubMed

    Dyer, J R; Greenwood, C E

    1991-10-01

    This experiment examined the time course over which the amount of dietary essential fatty acids (EFA) affects brain mitochondrial fatty acids. Weanling rats were fed 20% (wt/wt) fat diets that contained either 4 or 15% (wt/wt of diet) EFA for 1, 2, 3 or 6 wk or a 10% EFA diet for 3 or 6 wk. The EFA ratio [18:2(n-6)/18:3(n-3)] of all diets was approximately 30. Fatty acid analysis of brain mitochondrial phosphatidylethanolamine, phosphatidylcholine and cardiolipin revealed that the largest dietary effect was on 18:2(n-6), which was 30% higher in rats fed the 15 vs. 4% EFA diets after 1 wk. This difference increased to twofold by 3 wk and was still twofold after 6 wk. These results demonstrate several facts: 1) the response of 18:2(n-6) in cardiolipin to dietary EFA is very fast and large, relative to changes in other quantitatively major fatty acids observed in weanling rats; 2) the 18:2(n-6) level in neural cardiolipin stabilizes after 3 wk of feeding at a level dependent upon the amount of dietary EFA; and 3) at least one neural fatty acid, 18:2(n-6), is very sensitive to amounts of dietary EFA that are well above the animal's EFA requirement. PMID:1765818

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

    PubMed Central

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

    2015-01-01

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

  1. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

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

    2009-06-01

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

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

    PubMed

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

    2008-02-01

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

  3. The kinetic behaviour of the cranial neural epithelium during neurulation in the rat.

    PubMed

    Tuckett, F; Morriss-Kay, G M

    1985-02-01

    The kinetic behaviour of the cranial neuroepithelial cells of rat embryos during neurulation is described. Serial transverse sections of 4-, 8-, 12- and 16-somite-stage embryos show that differential mitosis does not play a part in the mechanisms responsible for effecting cranial neural tube closure. A constant cell number is found in the midbrain/hindbrain neural epithelium during all four stages; the mitotic spindle axes are oriented parallel to the long axis of the embryo, so that increase in cell number occurs in this direction only. Growth is only expressed by an expansion in the volume of the forebrain, which projects rostral to the notochordal tip. [3H]thymidine studies (using an in vitro culture technique) show no significant variation in the cell cycle time between the forebrain and the midbrain/anterior hindbrain neural epithelium. It is suggested that the neural epithelium is a fluid structure whose overall shape is strictly controlled while the cells within it flow towards and into the rapidly expanding forebrain. PMID:3989446

  4. Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat.

    PubMed

    Matthews, Keith; Robbins, Trevor W

    2003-01-01

    Depression is a major public health concern, representing one of the most significant causes of disability and morbidity. Despite significant advances in the definition of specific cognitive, emotional and neural dysfunctions that are associated with depression, there has been frustratingly little progress in the elucidation of plausible aetiological and pathophysiological mechanisms. The complex, multi-system dysfunctions of depressive illness do not lend themselves to hypothesis-driven, systematic manipulation in patients. For this reason, there is a need to develop valid and reliable models of affective psychopathology in laboratory animals. In this paper, we review briefly some of our previous work demonstrating that a specific periodic neonatal maternal separation procedure leads to a robust constellation of behavioural changes in the adult rat that resemble core aspects of human depressive psychopathology. We also present data from a study of the adult effects of the same manipulation on electrical intracranial self-stimulation behaviour. These data further support the hypothesis that it is possible to model vulnerability to anhedonia in the adult rat by manipulation of early experience. PMID:12732222

  5. SIRT1 suppresses self-renewal of adult hippocampal neural stem cells.

    PubMed

    Ma, Chen-Yan; Yao, Mao-jin; Zhai, Qi-wei; Jiao, Jian-wei; Yuan, Xiao-bing; Poo, Mu-ming

    2014-12-01

    The balance between self-renewal and differentiation of adult neural stem cells (aNSCs) is essential for the maintenance of the aNSC reservoir and the continuous supply of new neurons, but how this balance is fine-tuned in the adult brain is not fully understood. Here, we investigate the role of SIRT1, an important metabolic sensor and epigenetic repressor, in regulating adult hippocampal neurogenesis in mice. We found that there was an increase in SIRT1 expression during aNSC differentiation. In Sirt1 knockout (KO) mice, as well as in brain-specific and inducible stem cell-specific conditional KO mice, the proliferation and self-renewal rates of aNSCs in vivo were elevated. Proliferation and self-renewal rates of aNSCs and adult neural progenitor cells (aNPCs) were also elevated in neurospheres derived from Sirt1 KO mice and were suppressed by the SIRT1 agonist resveratrol in neurospheres from wild-type mice. In cultured neurospheres, 2-deoxy-D-glucose-induced metabolic stress suppressed aNSC/aNPC proliferation, and this effect was mediated in part by elevating SIRT1 activity. Microarray and biochemical analysis of neurospheres suggested an inhibitory effect of SIRT1 on Notch signaling in aNSCs/aNPCs. Inhibition of Notch signaling by a γ-secretase inhibitor also largely abolished the increased aNSC/aNPC proliferation caused by Sirt1 deletion. Together, these findings indicate that SIRT1 is an important regulator of aNSC/aNPC self-renewal and a potential mediator of the effect of metabolic changes. PMID:25468938

  6. Neural Correlates of Dual-Task Walking: Effects of Cognitive versus Motor Interference in Young Adults

    PubMed Central

    Beurskens, Rainer; Steinberg, Fabian; Antoniewicz, Franziska; Wolff, Wanja; Granacher, Urs

    2016-01-01

    Walking while concurrently performing cognitive and/or motor interference tasks is the norm rather than the exception during everyday life and there is evidence from behavioral studies that it negatively affects human locomotion. However, there is hardly any information available regarding the underlying neural correlates of single- and dual-task walking. We had 12 young adults (23.8 ± 2.8 years) walk while concurrently performing a cognitive interference (CI) or a motor interference (MI) task. Simultaneously, neural activation in frontal, central, and parietal brain areas was registered using a mobile EEG system. Results showed that the MI task but not the CI task affected walking performance in terms of significantly decreased gait velocity and stride length and significantly increased stride time and tempo-spatial variability. Average activity in alpha and beta frequencies was significantly modulated during both CI and MI walking conditions in frontal and central brain regions, indicating an increased cognitive load during dual-task walking. Our results suggest that impaired motor performance during dual-task walking is mirrored in neural activation patterns of the brain. This finding is in line with established cognitive theories arguing that dual-task situations overstrain cognitive capabilities resulting in motor performance decrements. PMID:27200192

  7. Biphasic change of progenitor proliferation in dentate gyrus after single dose of isoflurane in young adult rats

    PubMed Central

    Lin, Nan; Moon, Tiffany Sun; Stratmann, Greg; Sall, Jeffrey W.

    2013-01-01

    Background Isoflurane exposure causes improvement in long-term neurocognitive function in young adult rats, this is associated with an increase in dentate gyrus progenitor proliferation 4 days after anesthesia. However, the number of new neurons, that were born from cells that incorporated bromodeoxyuridine 4 days after anesthesia is not affected by anesthesia. We tested the hypothesis that progenitor proliferation continues to increase past 4 days, which would imply the possibility that the number of new neurons after anesthesia could be increased if bromodeoxyuridine labeling occurred at a later time point. Methods Bromodeoxyuridine was injected at 0, 1, 2, 4, 9, 16 days after 4 hours of isoflurane exposure to 60-day old rats. Brains were harvested 2 hours later, immunohistochemically stained, and the number of bromodeoxyuridine-positive cells in the dentate gyrus was assessed microscopically. Results After 4 hours of exposure to isoflurane in 60-day old rats, the number of bromodeoxyuridine-positive cells decreased on days 0–2, then increased on day 4 significantly, and regressed toward the control level on day 9 and 16. Conclusions Anesthesia-induced progenitor proliferation in the dentate gyrus was not sustained 9 days after anesthesia. We interpret these results to signify that an anesthetic effect on neurogenesis likely does not play a critical role in the previously observed isoflurane-induced long-term improvement in neurocognitive function in 60-day old rats and that the transient increase in progenitor proliferation serves to replenish the pool of neural stem cells. The mechanism of anesthesia-induced improvement in cognition of young adult rats remains elusive. PMID:23752046

  8. Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

    PubMed Central

    Gamm, David M.; Wang, Shaomei; Lu, Bin; Girman, Sergei; Holmes, Toby; Bischoff, Nicholas; Shearer, Rebecca L.; Sauvé, Yves; Capowski, Elizabeth; Svendsen, Clive N.; Lund, Raymond D.

    2007-01-01

    Background A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. Methodology/Principal Findings Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. Conclusions/Significance Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest

  9. Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish

    PubMed Central

    Hui, Subhra Prakash; Nag, Tapas Chandra; Ghosh, Sukla

    2015-01-01

    Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration. PMID:26630262

  10. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    SciTech Connect

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  11. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context

    PubMed Central

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J.; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3+ or BrdU+ cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3+), astroglia (GFAP+), and microglia (Iba1+ cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3+ and BrdU+ subgranular cells as well as GFAP+, Iba1+ and cleaved caspase-3+ cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3+, GFAP+ and 3-weeks-old BrdU+ cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. PMID:25870539

  12. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

    PubMed

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context. PMID:25870539

  13. β1-integrin restricts astrocytic differentiation of adult hippocampal neural stem cells.

    PubMed

    Brooker, Sarah M; Bond, Allison M; Peng, Chian-Yu; Kessler, John A

    2016-07-01

    Integrins are transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions. The β1-integrin subunit is highly expressed by embryonic neural stem cells (NSCs) and is critical for NSC maintenance in the developing nervous system, but its role in the adult hippocampal niche remains unexplored. We show that β1-integrin expression in the adult mouse dentate gyrus (DG) is localized to radial NSCs and early progenitors, but is lost in more mature progeny. Although NSCs in the hippocampal subgranular zone (SGZ) normally only infrequently differentiate into astrocytes, deletion of β1-integrin significantly enhanced astrocyte differentiation. Ablation of β1-integrin also led to reduced neurogenesis as well as depletion of the radial NSC population. Activation of integrin-linked kinase (ILK) in cultured adult NSCs from β1-integrin knockout mice reduced astrocyte differentiation, suggesting that at least some of the inhibitory effects of β1-integrin on astrocytic differentiation are mediated through ILK. In addition, β1-integrin conditional knockout also resulted in extensive cellular disorganization of the SGZ as well as non-neurogenic regions of the DG. The effects of β1-integrin ablation on DG structure and astrogliogenesis show sex-specific differences, with the effects following a substantially slower time-course in males. β1-integrin thus plays a dual role in maintaining the adult hippocampal NSC population by supporting the structural integrity of the NSC niche and by inhibiting astrocytic lineage commitment. GLIA 2016;64:1235-1251. PMID:27145730

  14. Nogo Receptor Signaling Restricts Adult Neural Plasticity by Limiting Synaptic AMPA Receptor Delivery

    PubMed Central

    Jitsuki, Susumu; Nakajima, Waki; Takemoto, Kiwamu; Sano, Akane; Tada, Hirobumi; Takahashi-Jitsuki, Aoi; Takahashi, Takuya

    2016-01-01

    Experience-dependent plasticity is limited in the adult brain, and its molecular and cellular mechanisms are poorly understood. Removal of the myelin-inhibiting signaling protein, Nogo receptor (NgR1), restores adult neural plasticity. Here we found that, in NgR1-deficient mice, whisker experience-driven synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) insertion in the barrel cortex, which is normally complete by 2 weeks after birth, lasts into adulthood. In vivo live imaging by two-photon microscopy revealed more AMPAR on the surface of spines in the adult barrel cortex of NgR1-deficient than on those of wild-type (WT) mice. Furthermore, we observed that whisker stimulation produced new spines in the adult barrel cortex of mutant but not WT mice, and that the newly synthesized spines contained surface AMPAR. These results suggest that Nogo signaling limits plasticity by restricting synaptic AMPAR delivery in coordination with anatomical plasticity. PMID:26472557

  15. Neural correlates of source memory retrieval in young, middle-aged and elderly adults.

    PubMed

    Cansino, Selene; Hernández-Ramos, Evelia; Trejo-Morales, Patricia

    2012-04-01

    Event-related potentials (ERPs) were recorded in young (21-27 years old), middle-aged (50-57 years old) and older adults (70-77 years old) to determine whether the decline in source memory that occurs with advancing age coincides with contemporaneous neurophysiological changes. Source memory for the spatial location (quadrant on the screen) of images presented during encoding was examined. The images were shown in the center of the screen during the retrieval task. Retrieval success for source information was characterized by different scalp topographies at frontal electrode sites in young adults relative to middle-aged and older adults. The right frontal effect during unsuccessful retrieval attempts showed amplitude and latency differences across age groups and was related to the ability to discriminate between old and new images only in young adults. These results suggest that the neural correlates of the retrieval success and attempt were affected by age and these effects were present by middle-age. PMID:22366225

  16. Delphinium alkaloids as inhibitors of alpha-bungarotoxin binding to rat and insect neural membranes.

    PubMed

    Kukel, C F; Jennings, K R

    1994-01-01

    A series of C19-diterpenoid alkaloids purified from Delphinium were evaluated as inhibitors of alpha-bungarotoxin binding to rat and house fly neural membranes. In comparing these diterpenoid analogs, a wide range of inhibition potencies (IC50) were observed, with calculated IC50 values ranging six orders of magnitude. The most potent inhibitory alkaloids in this series possessed the succinimide aromatic ester moiety in the C18 position. Glaudelsine had an IC50 value of 42 pM at the insect nicotinic acetylcholine receptor. PMID:8012891

  17. Neural Resolution of Formant Frequencies in the Primary Auditory Cortex of Rats

    PubMed Central

    Honey, Christian; Schnupp, Jan

    2015-01-01

    Pulse-resonance sounds play an important role in animal communication and auditory object recognition, yet very little is known about the cortical representation of this class of sounds. In this study we shine light on one simple aspect: how well does the firing rate of cortical neurons resolve resonant (“formant”) frequencies of vowel-like pulse-resonance sounds. We recorded neural responses in the primary auditory cortex (A1) of anesthetized rats to two-formant pulse-resonance sounds, and estimated their formant resolving power using a statistical kernel smoothing method which takes into account the natural variability of cortical responses. While formant-tuning functions were diverse in structure across different penetrations, most were sensitive to changes in formant frequency, with a frequency resolution comparable to that reported for rat cochlear filters. PMID:26252382

  18. GONADAL STEROIDS REGULATED THE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN THE ADULT MALE RAT HIPPOCAMPUS

    EPA Science Inventory

    This study demonstrates that gonadal steroids (estradiol, testosterone, dihydrotestosterone) can inhibit the expression of glial fibrillary acidic protein and it MRNA in the adult male rat brain. esticular hormones may influence the activity of astrocytes in the intact and lesion...

  19. Generation of New Neurons in Dorsal Root Ganglia in Adult Rats after Peripheral Nerve Crush Injury

    PubMed Central

    2015-01-01

    The evidence of neurons generated ex novo in sensory ganglia of adult animals is still debated. In the present study, we investigated, using high resolution light microscopy and stereological analysis, the changes in the number of neurons in dorsal root ganglia after 30 days from a crush lesion of the rat brachial plexus terminal branches. Results showed, as expected, a relevant hypertrophy of dorsal root ganglion neurons. In addition, we reported, for the first time in the literature, that neuronal hypertrophy was accompanied by massive neuronal hyperplasia leading to a 42% increase of the number of primary sensory neurons. Moreover, ultrastructural analyses on sensory neurons showed that there was not a relevant neuronal loss as a consequence of the nerve injury. The evidence of BrdU-immunopositive neurons and neural progenitors labeled with Ki67, nanog, nestin, and sox-2 confirmed the stereological evidence of posttraumatic neurogenesis in dorsal root ganglia. Analysis of morphological changes following axonal damage in addition to immunofluorescence characterization of cell phenotype suggested that the neuronal precursors which give rise to the newly generated neurons could be represented by satellite glial cells that actively proliferate after the lesion and are able to differentiate toward the neuronal lineage. PMID:25722894

  20. Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2

    PubMed Central

    Kirby, Elizabeth D; Muroy, Sandra E; Sun, Wayne G; Covarrubias, David; Leong, Megan J; Barchas, Laurel A; Kaufer, Daniela

    2013-01-01

    Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain. DOI: http://dx.doi.org/10.7554/eLife.00362.001 PMID:23599891

  1. Spinal Interneurons and Forelimb Plasticity after Incomplete Cervical Spinal Cord Injury in Adult Rats

    PubMed Central

    Rombola, Angela M.; Rousseau, Celeste A.; Mercier, Lynne M.; Fitzpatrick, Garrett M.; Reier, Paul J.; Fuller, David D.; Lane, Michael A.

    2015-01-01

    Abstract Cervical spinal cord injury (cSCI) disrupts bulbospinal projections to motoneurons controlling the upper limbs, resulting in significant functional impairments. Ongoing clinical and experimental research has revealed several lines of evidence for functional neuroplasticity and recovery of upper extremity function after SCI. The underlying neural substrates, however, have not been thoroughly characterized. The goals of the present study were to map the intraspinal motor circuitry associated with a defined upper extremity muscle, and evaluate chronic changes in the distribution of this circuit following incomplete cSCI. Injured animals received a high cervical (C2) lateral hemisection (Hx), which compromises supraspinal input to ipsilateral spinal motoneurons controlling the upper extremities (forelimb) in the adult rat. A battery of behavioral tests was used to characterize the time course and extent of forelimb motor recovery over a 16 week period post-injury. A retrograde transneuronal tracer – pseudorabies virus – was used to define the motor and pre-motor circuitry controlling the extensor carpi radialis longus (ECRL) muscle in spinal intact and injured animals. In the spinal intact rat, labeling was observed unilaterally within the ECRL motoneuron pool and within spinal interneurons bilaterally distributed within the dorsal horn and intermediate gray matter. No changes in labeling were observed 16 weeks post-injury, despite a moderate degree of recovery of forelimb motor function. These results suggest that recovery of the forelimb function assessed following C2Hx injury does not involve recruitment of new interneurons into the ipsilateral ECRL motor pathway. However, the functional significance of these existing interneurons to motor recovery requires further exploration. PMID:25625912

  2. Expression of polysialyltransferases (STX and PST) in adult rat olfactory bulb after an olfactory associative discrimination task.

    PubMed

    Mione, J; Manrique, C; Duhoo, Y; Roman, F S; Guiraudie-Capraz, G

    2016-04-01

    Neuronal plasticity and neurogenesis occur in the adult hippocampus and in other brain structures such as the olfactory bulb and often involve the neural cell adhesion molecule NCAM. During an olfactory associative discrimination learning task, NCAM polysialylation triggers neuronal plasticity in the adult hippocampus. The PST enzyme likely modulates this polysialylation, but not STX, a second sialyltransferase. How the two polysialyltransferases are involved in the adult olfactory bulb remains unknown. We addressed this question by investigating the effect of olfactory associative learning on plasticity and neurogenesis. After a hippocampo-dependent olfactory associative task learning, we measured the expression of both PST and STX polysialyltransferases in the olfactory bulbs of adult rats using quantitative PCR. In parallel, immunohistochemistry was used to evaluate both NCAM polysialylation level and newly-born cells, with or without learning. After learning, no changes were observed neither in the expression level of PST and NCAM polysialylation, nor in STX gene expression level and newly-born cells number in the olfactory bulb. PMID:26844880

  3. Insular neural system controls decision-making in healthy and methamphetamine-treated rats.

    PubMed

    Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

    2015-07-21

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making. PMID:26150496

  4. Insular neural system controls decision-making in healthy and methamphetamine-treated rats

    PubMed Central

    Mizoguchi, Hiroyuki; Katahira, Kentaro; Inutsuka, Ayumu; Fukumoto, Kazuya; Nakamura, Akihiro; Wang, Tian; Nagai, Taku; Sato, Jun; Sawada, Makoto; Ohira, Hideki; Yamanaka, Akihiro; Yamada, Kiyofumi

    2015-01-01

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making. PMID:26150496

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

    PubMed

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

    2015-08-01

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

  6. IMMUNOTOXICITY OF TRIBUTYLTIN OXIDE IN RATS EXPOSED AS ADULTS OR PRE-WEANLINGS

    EPA Science Inventory

    A comparison was made between adult and pre-weanling rats of the immunotoxic effects of acute dosing with bis(tri-n-butyltin) oxide (TBT0). dult (9 week old) male Fischer rats were dosed by oral gavage with TBT0 for 10 consecutive days at 2.5 to 10 mg/kg/dose or three times per w...

  7. ALKYTIN INHIBITION OF ATPASE ACTIVITIES IN TISSUE HOMOGENATES AND SUBCELLULAR FRACTIONS FROM NEONATAL AND ADULT RATS

    EPA Science Inventory

    The effects of triethyltin (TET) on ATPase activities in brain and liver homogenates and subcellular fractions were compared in neonatal and adult rats. n 5 day old rats, relative sensitivities to TET inhibition were: brain and liver mitochondrial ATPase >> rain Na+/K+ ATPase > b...

  8. IMMATURE RAT LEYDIG CELLS ARE INTRINSICALLY LESS SENSITIVE THAN ADULT LEYDIG CELLS TO ETHANE DIMETHANESULFONATE

    EPA Science Inventory

    Leydig cells from immature rat tests appear to be insensitive to doses of ethane-1,2-dimethanesulfonate (EDS) which eliminate Leydig cells from adult rat testes. e sought to determine whether this differential response to EDS is intrinsic to the Leydig cell or mediated by other i...

  9. Spontaneous neural activity in the primary visual cortex of retinal degenerated rats.

    PubMed

    Wang, Yi; Chen, Ke; Xu, Ping; Ng, Tsz Kin; Chan, Leanne Lai Hang

    2016-06-01

    Retinal degeneration (RD) models have been widely used to study retinal degenerative diseases for a long time. The biological and electrophysiological presentations of changes in the retina during degeneration progress have been well investigated; thus, the present study is aimed at investigating the electrophysiological effects of RD in the primary visual cortex. We extracellularly recorded the spontaneous neural activities in the primary visual cortex of RD rats. The firing rate, interspike interval (ISI) and Lempel-Ziv (LZ) complexity of spontaneous neural activities were subsequently analyzed. When compared to the control group, it was found that the neurons in primary visual cortex of the RD model fired more frequently. In addition, there was a decrease in LZ complexity of spontaneous neural firing in the RD model. These results suggest that the progress of RD may not only affect the retina itself but also the primary visual cortex, which may result in an unbalanced inhibition-excitation system as well as the decreased arising rate of new patterns of spontaneous activities. PMID:27132087

  10. Miniaturized neural sensing and optogenetic stimulation system for behavioral studies in the rat

    NASA Astrophysics Data System (ADS)

    Kim, Min Hyuck; Nam, Ilho; Ryu, Youngki; Wellman, Laurie W.; Sanford, Larry D.; Yoon, Hargsoon

    2015-04-01

    Real time sensing of localized electrophysiological and neurochemical signals associated with spontaneous and evoked neural activity is critically important for understanding neural networks in the brain. Our goal is to enhance the functionality and flexibility of a neural sensing and stimulation system for the observation of brain activity that will enable better understanding from the level of individual cells to that of global structures. We have thus developed a miniaturized electronic system for in-vivo neurotransmitter sensing and optogenetic stimulation amenable to behavioral studies in the rat. The system contains a potentiostat, a data acquisition unit, a control unit, and a wireless data transfer unit. For the potentiostat, we applied embedded op-amps to build single potential amperometry for electrochemical sensing of dopamine. A light emitting diode is controlled by a microcontroller and pulse width modulation utilized to control optogenetic stimulation within a sub-millisecond level. In addition, this proto-typed electronic system contains a Bluetooth module for wireless data communication. In the future, an application-specific integrated circuit (ASIC) will be designed for further miniaturization of the system.

  11. Modeling habituation in rat EEG-evoked responses via a neural mass model with feedback

    PubMed Central

    Tadmor, Gilead; Diamond, Solomon G.; Miller, Eric; Franceschini, Maria Angela; Brooks, Dana H.

    2012-01-01

    Habituation is a generic property of the neural response to repeated stimuli. Its strength often increases as inter-stimuli relaxation periods decrease. We propose a simple, broadly applicable control structure that enables a neural mass model of the evoked EEG response to exhibit habituated behavior. A key motivation for this investigation is the ongoing effort to develop model-based reconstruction of multimodal functional neuroimaging data. The control structure proposed here is illustrated and validated in the context of a biophysical neural mass model, developed by Riera et al. (Hum Brain Mapp 27(11):896–914, 2006; 28(4):335–354, 2007), and of simplifications thereof, using data from rat EEG response to medial nerve stimuli presented at frequencies from 1 to 8 Hz. Performance was tested by predictions of both the response to the next stimulus based on the current one, and also of continued stimuli trains over 4-s time intervals based on the first stimulus in the interval, with similar success statistics. These tests demonstrate the ability of simple generative models to capture key features of the evoked response, including habituation. PMID:22282292

  12. Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats.

    PubMed

    Bakker, J M; Kavelaars, A; Kamphuis, P J; Cobelens, P M; van Vugt, H H; van Bel, F; Heijnen, C J

    2000-11-15

    Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.01) of the inflammatory autoimmune disease experimental autoimmune encephalomyelitis in adult life. In search of possible mechanisms responsible for the increased susceptibility to experimental autoimmune encephalomyelitis, we investigated the reactivity of the hypothalamo-pituitary-adrenal axis and of immune cells in adult rats after neonatal glucocorticoid treatment. We observed that neonatal glucocorticoid treatment reduces the corticosterone response after an LPS challenge in adult rats (p< or =0.001). Interestingly, LPS-stimulated macrophages of glucocorticoid-treated rats produce less TNF-alpha and IL-1beta in adult life than control rats (p<0.05). In addition, splenocytes obtained from adult rats express increased mRNA levels of the proinflammatory cytokines IFN-gamma (p<0.01) and TNF-beta (p<0.05) after neonatal glucocorticoid treatment. Apparently, neonatal glucocorticoid treatment has permanent programming effects on endocrine as well as immune functioning in adult life. In view of the frequent clinical application of glucocorticoids to preterm infants, our data demonstrate that neonatal glucocorticoid treatment may be a risk factor for the development of (auto)immune disease in man. PMID:11067955

  13. Social and Hormonal Triggers of Neural Plasticity in Naked Mole-Rats

    PubMed Central

    Holmes, Melissa M.; Seney, Marianne L.; Goldman, Bruce D.; Forger, Nancy G.

    2010-01-01

    Naked mole-rats are eusocial rodents that live in large social groups with a strict reproductive hierarchy. In each colony only a few individuals breed; all others are non-reproductive subordinates. We previously showed that breeders have increased volume of several brain regions linked to reproduction: the paraventricular nucleus of the hypothalamus (PVN), the principal nucleus of the bed nucleus of the stria terminalis (BSTp), and the medial amygdala (MeA). Breeders also have more large motoneurons in Onuf’s nucleus (ON) in the spinal cord, a cell group innervating perineal muscles that attach to the genitalia. Here, we sought to determine triggers for the neural changes seen in breeders. Specifically, we compared four groups of animals: subordinates, paired animals that did not reproduce, gonadally intact breeders, and gonadectomized breeders. We find that pairing alone is sufficient to cause breeder-like changes in volume of the PVN and cell size distribution in ON. In contrast, increases in BSTp volume were seen only in animals that actually reproduced. Those changes that were seen in successful breeders appear to be independent of gonadal steroids because long-term gonadectomy did not reverse the breeder-like neural changes in the PVN, BSTp or ON, although a trend for gonadectomized animals having larger MeA volumes was detected. Thus, neural changes associated with breeding status in naked mole-rats may be triggered by different aspects of the social and reproductive environment; once changes occur they are largely independent of gonadal hormones and may be permanent. PMID:21130812

  14. Human olfactory bulb neural stem cells mitigate movement disorders in a rat model of Parkinson's disease.

    PubMed

    Marei, Hany E S; Lashen, Samah; Farag, Amany; Althani, Asmaa; Afifi, Nahla; A, Abd-Elmaksoud; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-07-01

    Parkinson's disease (PD) is a neurological disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells (NSCs) are multipotent stem cells that are capable of differentiating into different neuronal and glial elements. The production of DA neurons from NSCs could potentially alleviate behavioral deficits in Parkinsonian patients; timely intervention with NSCs might provide a therapeutic strategy for PD. We have isolated and generated highly enriched cultures of neural stem/progenitor cells from the human olfactory bulb (OB). If NSCs can be obtained from OB, it would alleviate ethical concerns associated with the use of embryonic tissue, and provide an easily accessible cell source that would preclude the need for invasive brain surgery. Following isolation and culture, olfactory bulb neural stem cells (OBNSCs) were genetically engineered to express hNGF and GFP. The hNFG-GFP-OBNSCs were transplanted into the striatum of 6-hydroxydopamin (6-OHDA) Parkinsonian rats. The grafted cells survived in the lesion environment for more than eight weeks after implantation with no tumor formation. The grafted cells differentiated in vivo into oligodendrocyte-like (25 ± 2.88%), neuron-like (52.63 ± 4.16%), and astrocyte -like (22.36 ± 1.56%) lineages, which we differentiated based on morphological and immunohistochemical criteria. Transplanted rats exhibited a significant partial correction in stepping and placing in non-pharmacological behavioral tests, pole and rotarod tests. Taken together, our data encourage further investigations of the possible use of OBNSCs as a promising cell-based therapeutic strategy for Parkinson's disease. PMID:25536543

  15. Long-term oral methylphenidate treatment in adolescent and adult rats: differential effects on brain morphology and function.

    PubMed

    van der Marel, Kajo; Klomp, Anne; Meerhoff, Gideon F; Schipper, Pieter; Lucassen, Paul J; Homberg, Judith R; Dijkhuizen, Rick M; Reneman, Liesbeth

    2014-01-01

    Methylphenidate is a widely prescribed psychostimulant for treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents, which raises questions regarding its potential interference with the developing brain. In the present study, we investigated effects of 3 weeks oral methylphenidate (5 mg/kg) vs vehicle treatment on brain structure and function in adolescent (post-natal day [P]25) and adult (P65) rats. Following a 1-week washout period, we used multimodal magnetic resonance imaging (MRI) to assess effects of age and treatment on independent component analysis-based functional connectivity (resting-state functional MRI), D-amphetamine-induced neural activation responses (pharmacological MRI), gray and white matter tissue volumes and cortical thickness (postmortem structural MRI), and white matter structural integrity (postmortem diffusion tensor imaging (DTI)). Many age-related differences were found, including cortical thinning, white matter development, larger dopamine-mediated activation responses and increased striatal functional connectivity. Methylphenidate reduced anterior cingulate cortical network strength in both adolescents and adults. In contrast to clinical observations from ADHD patient studies, methylphenidate did not increase white matter tissue volume or cortical thickness in rat. Nevertheless, DTI-based fractional anisotropy was higher in the anterior part of the corpus callosum following adolescent treatment. Furthermore, methylphenidate differentially affected adolescents and adults as evidenced by reduced striatal volume and myelination upon adolescent treatment, although we did not observe adverse treatment effects on striatal functional activity. Our findings of small but significant age-dependent effects of psychostimulant treatment in the striatum of healthy rats highlights the importance of further research in children and adolescents that are exposed to methylphenidate. PMID:23851400

  16. Attenuation of the hypoxic ventilatory response in adult rats following one month of perinatal hyperoxia.

    PubMed Central

    Ling, L; Olson, E B; Vidruk, E H; Mitchell, G S

    1996-01-01

    1. This study was designed to test the hypothesis that perinatal suppression of peripheral arterial chemoreceptor inputs attenuates the hypoxic ventilatory response in adult rats. Perinatal suppression of peripheral chemoreceptor activity was achieved by exposing rats to hyperoxia throughout the first month of life. 2. Late-gestation pregnant rats were housed in a 60% O2 environment, exposing the pups to hyperoxia from several days prior to birth until they were returned to normoxia on postnatal day 28. These perinatally treated rats were then reared to adulthood (3-5 months old) in normoxia. In addition to the mother rats, adult male rats were also exposed to hyperoxia, creating an adult-treated control group. Two to four months after the hyperoxic exposure, treated rats were compared with untreated male rats of similar age. 3. A whole-body, flow-through plethysmograph was used to measure hypoxic and hypercapnic ventilatory responses of the unanaesthetized adult rats. In moderate hypoxia (arterial oxygen partial pressure, Pa,O2 approximately 48 mmHg). VE (minute ventilation) and the ratio VE/VCO2 (ventilation relative to CO2 production) increased by 16.7 +/- 4.0 and 35.4 +/- 3.4%, respectively, in perinatal-treated rats (means +/- S.E.M.), but increased more in untreated control rats (51.4 +/- 2.8 and 83.1 +/- 4.3%; both P < 10(-6)). 4. In contrast to the impaired hypoxic ventilatory response, ventilatory responses to hypercapnia (5% CO2) were similar between untreated control and perinatal-treated rats. 5. Impaired hypoxic responsiveness was unique to the perinatal-treated rats since hypoxic ventilatory responses were not attenuated in adult-treated rats. 6. The results indicate that ventilatory responses to hypoxaemia are greatly attenuated in adult rats that had experienced hyperoxia during their first month of life, and suggest that normal hypoxic ventilatory control mechanisms are susceptible to developmental plasticity. Images Figure 2 Figure 3 PMID:8887766

  17. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells.

    PubMed

    Regnell, Christine Elisabeth; Hildrestrand, Gunn Annette; Sejersted, Yngve; Medin, Tirill; Moldestad, Olve; Rolseth, Veslemøy; Krokeide, Silje Zandstra; Suganthan, Rajikala; Luna, Luisa; Bjørås, Magnar; Bergersen, Linda H

    2012-09-27

    Accumulation of oxidative DNA damage has been proposed as a potential cause of age-related cognitive decline. The major pathway for removal of oxidative DNA base lesions is base excision repair, which is initiated by DNA glycosylases. In mice, Neil3 is the main DNA glycosylase for repair of hydantoin lesions in single-stranded DNA of neural stem/progenitor cells, promoting neurogenesis. Adult neurogenesis is crucial for maintenance of hippocampus-dependent functions involved in behavior. Herein, behavioral studies reveal learning and memory deficits and reduced anxiety-like behavior in Neil3(-/-) mice. Neural stem/progenitor cells from aged Neil3(-/-) mice show impaired proliferative capacity and reduced DNA repair activity. Furthermore, hippocampal neurons in Neil3(-/-) mice display synaptic irregularities. It appears that Neil3-dependent repair of oxidative DNA damage in neural stem/progenitor cells is required for maintenance of adult neurogenesis to counteract the age-associated deterioration of cognitive performance. PMID:22959434

  18. The Effects of Simulated Stuttering and Prolonged Speech on the Neural Activation Patterns of Stuttering and Nonstuttering Adults

    ERIC Educational Resources Information Center

    De Nil, Luc F.; Beal, Deryk S.; Lafaille, Sophie J.; Kroll, Robert M.; Crawley, Adrian P.; Gracco, Vincent L.

    2008-01-01

    Functional magnetic resonance imaging was used to investigate the neural correlates of passive listening, habitual speech and two modified speech patterns (simulated stuttering and prolonged speech) in stuttering and nonstuttering adults. Within-group comparisons revealed increased right hemisphere biased activation of speech-related regions…

  19. Electroconvulsive seizure induces thrombospondin-1 in the adult rat hippocampus.

    PubMed

    Okada-Tsuchioka, Mami; Segawa, Masahiro; Kajitani, Naoto; Hisaoka-Nakashima, Kazue; Shibasaki, Chiyo; Morinobu, Shigeru; Takebayashi, Minoru

    2014-01-01

    Synaptic dysfunction has recently gained attention for its involvement in mood disorders. Electroconvulsive therapy (ECT) possibly plays a role in synaptic repair. However, the underlying mechanisms remain uncertain. Thrombospondin-1 (TSP-1), a member of the TSP family, is reported to be secreted by astrocytes and to regulate synaptogenesis. We investigated the effects of electroconvulsive seizure (ECS) on the expression of TSPs in the adult rat hippocampus. Single and repeated ECS significantly increased TSP-1 mRNA expression after 2h and returned to sham levels at 24h. Conversely, the TSP-2 and -4 mRNA levels did not change. Only repeated ECS induced TSP-1 proteins. ECS also induced glial fibrillary acidic protein (GFAP) expression. The GFAP expression occurred later than the TSP-1 mRNA expression following single ECS; however, it occurred earlier and was more persistent following repeated ECS. ECS had no effect on the α2δ-1 or neuroligin-1 expressions, both of which are TSP-1 receptors. Furthermore, chronic treatment with antidepressants did not induce the expression of TSP-1 or GFAP. These findings suggest that repeated ECS, but not chronic treatment with antidepressants, induces TSP-1 expression partially via the activation of astrocytes. Therefore, TSP-1 is possibly involved in the synaptogenic effects of ECS. PMID:24121060

  20. Adversity before conception will affect adult progeny in rats.

    PubMed

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress (PCS0) or 2 weeks after the stress ended (PCS2). Their offspring were raised undisturbed until tested in adulthood. PCS offspring showed reduced social interaction; in the acoustic startle test, PCS males were less fearful, whereas PCS females were more fearful; in the shuttle task, PCS0 males avoided shock better; and in the elevated maze, PCS0 females were more active and anxious. The 2-week interval between stress and mating assuaged the effects on offspring activity and shock avoidance but not the changes in social behavior and fear in male and female offspring. Hence, PCS to the dam, even well before pregnancy, influences affective and social behavior in her adult offspring, depending on how long before conception it occurred, the behavior tested, and sex. (PsycINFO Database Record (c) 2009 APA, all rights reserved). PMID:19209986

  1. Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence

    PubMed Central

    Reske, Martina; Stewart, Jennifer L.; Flagan, Taru M.; Paulus, Martin P.

    2015-01-01

    Objective Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing. Methods 158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a “risky gains” decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, “risky decisions”). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed. Results There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options. Discussion Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions

  2. Designer Self-Assembling Peptide Nanofiber Scaffolds for Adult Mouse Neural Stem Cell 3-Dimensional Cultures

    PubMed Central

    Gelain, Fabrizio; Bottai, Daniele; Vescovi, Angleo; Zhang, Shuguang

    2006-01-01

    Biomedical researchers have become increasingly aware of the limitations of conventional 2-dimensional tissue cell culture systems, including coated Petri dishes, multi-well plates and slides, to fully address many critical issues in cell biology, cancer biology and neurobiology, such as the 3-D microenvironment, 3-D gradient diffusion, 3-D cell migration and 3-D cell-cell contact interactions. In order to fully understand how cells behave in the 3-D body, it is important to develop a well-controlled 3-D cell culture system where every single ingredient is known. Here we report the development of a 3-D cell culture system using a designer peptide nanofiber scaffold with mouse adult neural stem cells. We attached several functional motifs, including cell adhesion, differentiation and bone marrow homing motifs, to a self-assembling peptide RADA16 (Ac-RADARADARADARADA-COHN2). These functionalized peptides undergo self-assembly into a nanofiber structure similar to Matrigel. During cell culture, the cells were fully embedded in the 3-D environment of the scaffold. Two of the peptide scaffolds containing bone marrow homing motifs significantly enhanced the neural cell survival without extra soluble growth and neurotrophic factors to the routine cell culture media. In these designer scaffolds, the cell populations with β-Tubulin+, GFAP+ and Nestin+ markers are similar to those found in cell populations cultured on Matrigel. The gene expression profiling array experiments showed selective gene expression, possibly involved in neural stem cell adhesion and differentiation. Because the synthetic peptides are intrinsically pure and a number of desired function cellular motifs are easy to incorporate, these designer peptide nanofiber scaffolds provide a promising controlled 3-D culture system for diverse tissue cells, and are useful as well for general molecular and cell biology. PMID:17205123

  3. The influence of early maternal care on perceptual attentional set shifting and stress reactivity in adult rats.

    PubMed

    Sakhai, Samuel A; Saxton, Katherine; Francis, Darlene D

    2016-01-01

    Stress influences a wide variety of outcomes including cognitive processing. In the rat, early life maternal care can influence developing offspring to affect both stress reactivity and cognitive processes in adulthood. The current study assessed if variations in early life maternal care can influence cognitive performance on a task, the ability to switch cognitive sets, dependent on the medial prefrontal cortex. Early in life, offspring was reared under High or Low maternal Licking conditions. As adults, they were trained daily and then tested on an attentional set-shifting task (ASST), which targets cognitive flexibility in rodents. Stress-sensitive behavioral and neural markers were assayed before and after the ASST. High and Low Licking offspring performed equally well on the ASST despite initial, but not later, differences in stress axis functioning. These results suggest that early life maternal care does not impact the accuracy of attentional set-shifting in rats. These findings may be of particular importance for those interested in the relationship between early life experience and adult cognitive function. PMID:26289990

  4. Human neural progenitors differentiate into astrocytes and protect motor neurons in aging rats.

    PubMed

    Das, Melanie M; Avalos, Pablo; Suezaki, Patrick; Godoy, Marlesa; Garcia, Leslie; Chang, Christine D; Vit, Jean-Philippe; Shelley, Brandon; Gowing, Genevieve; Svendsen, Clive N

    2016-06-01

    Age-associated health decline presents a significant challenge to healthcare, although there are few animal models that can be used to test potential treatments. Here, we show that there is a significant reduction in both spinal cord motor neurons and motor function over time in the aging rat. One explanation for this motor neuron loss could be reduced support from surrounding aging astrocytes. Indeed, we have previously shown using in vitro models that aging rat astrocytes are less supportive to rat motor neuron function and survival over time. Here, we test whether rejuvenating the astrocyte niche can improve the survival of motor neurons in an aging spinal cord. We transplanted fetal-derived human neural progenitor cells (hNPCs) into the aging rat spinal cord and found that the cells survive and differentiate into astrocytes with a much higher efficiency than when transplanted into younger animals, suggesting that the aging environment stimulates astrocyte maturation. Importantly, the engrafted astrocytes were able to protect against motor neuron loss associated with aging, although this did not result in an increase in motor function based on behavioral assays. We also transplanted hNPCs genetically modified to secrete glial cell line-derived neurotrophic factor (GDNF) into the aging rat spinal cord, as this combination of cell and protein delivery can protect motor neurons in animal models of ALS. During aging, GDNF-expressing hNPCs protected motor neurons, though to the same extent as hNPCs alone, and again had no effect on motor function. We conclude that hNPCs can survive well in the aging spinal cord, protect motor neurons and mature faster into astrocytes when compared to transplantation into the young spinal cord. While there was no functional improvement, there were no functional deficits either, further supporting a good safety profile of hNPC transplantation even into the older patient population. PMID:27032721

  5. Prospective identification and culture of rat enteric neural stem cells (ENSCs).

    PubMed

    Gao, Tingting; Chen, Haijiao; Liu, Mei; Ge, Wenliang; Yin, Qiyou

    2016-05-01

    Hirschprung's disease (HD), a very common congenital abnormality in children, occurs mainly due to the congenital developmental defect of the enteric nervous system. The absence of enteric ganglia from the distal gut due to deletion in gut colonization by neural crest progenitor cells may lead to HD. The capacity to identify and isolate the enteric neuronal precursor cells from developing and mature tissues would enable the development of cell replacement therapies for HD. However, a mature method to culture these cells is a challenge. The present study aimed to propose a method to culture enteric neural stem cells (ENSCs) from the DsRed transgenic fetal rat gut. The culture medium used contained 15 % chicken embryo extract, basic fibroblast growth factor, and epidermal growth factor. ENSCs were cultured from embryonic day 18 in DsRed transgenic rat. Under inverted microscope and fluorescence staining, ENSCs proliferated to form small cell clusters on the second day of culture. The neurospheres-like structure were suspended in the medium, and there were some filaments between the adherent cells from day 3 to day 6 of the culture. The neurospheres were formed by ENSCs on day 8 of the culture. Network-like connections were formed between the adherent cells and differentiated cells after adding 10 % FBS. The differentiated cells were positive for neurofilament and glial fibrillary acidic protein antibodies. The present study established a method to isolate and culture ENSCs from E18 DsRed transgenic rats in the terminal stage of embryonic development. This study would offer a way to obtain plenty of cells for the future research on the transplantation of HD. PMID:25407731

  6. The Neural Basis of Nonvisual Object Recognition Memory in the Rat

    PubMed Central

    Albasser, Mathieu M.; Olarte-Sánchez, Cristian M.; Amin, Eman; Horne, Murray R.; Newton, Michael J.; Warburton, E. Clea; Aggleton, John P.

    2012-01-01

    Research into the neural basis of recognition memory has traditionally focused on the remembrance of visual stimuli. The present study examined the neural basis of object recognition memory in the dark, with a view to determining the extent to which it shares common pathways with visual-based object recognition. Experiment 1 assessed the expression of the immediate-early gene c-fos in rats that discriminated novel from familiar objects in the dark (Group Novel). Comparisons made with a control group that explored only familiar objects (Group Familiar) showed that Group Novel had higher c-fos activity in the rostral perirhinal cortex and the lateral entorhinal cortex. Outside the temporal region, Group Novel showed relatively increased c-fos activity in the anterior medial thalamic nucleus and the anterior cingulate cortex. Both the hippocampal CA fields and the granular retrosplenial cortex showed borderline increases in c-fos activity with object novelty. The hippocampal findings prompted Experiment 2. Here, rats with hippocampal lesions were tested in the dark for object recognition memory at different retention delays. Across two replications, no evidence was found that hippocampal lesions impair nonvisual object recognition. The results indicate that in the dark, as in the light, interrelated parahippocampal sites are activated when rats explore novel stimuli. These findings reveal a network of linked c-fos activations that share superficial features with those associated with visual recognition but differ in the fine details; for example, in the locus of the perirhinal cortex activation. While there may also be a relative increase in c-fos activation in the extended-hippocampal system to object recognition in the dark, there was no evidence that this recognition memory problem required an intact hippocampus. PMID:23244291

  7. Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2

    PubMed Central

    Reddy, Avanish S.; Maletic-Savatic, Mirjana; Aguirre, Adan; Tsirka, Stella E.

    2013-01-01

    Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2−/− mice exhibit SVZ hyperproliferation, increased numbers of SVZ NSCs, and a trend towards aberrant increases in newly born neurons in the olfactory bulb (OB) granule cell layer. Increases in the levels of the transcription factor p21 and the Neural cell adhesion molecule (NCAM), along with down-regulation of the transcription/pluripotency factor Oct4 in the Hmgb2−/− SVZ point to a possible pathway for this increased proliferation/differentiation. Our findings suggest that HMGB2 functions as a modulator of neurogenesis in young adult mice through regulation of NSC proliferation, and identify a potential target via which CNS repair could be amplified following trauma or disease-based neuronal degeneration. PMID:24391977

  8. Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats

    PubMed Central

    Glenn, Melissa J.; Gibson, Erin M.; Kirby, Elizabeth D.; Mellott, Tiffany J.; Blusztajn, Jan K.; Williams, Christina L.

    2008-01-01

    Increased dietary intake of choline early in life improves performance of adult rats on memory tasks and prevents their age-related memory decline. Because neurogenesis in the adult hippocampus also declines with age, we investigated whether prenatal choline availability affects hippocampal neurogenesis in adult Sprague–Dawley rats and modifies their neurogenic response to environmental stimulation. On embryonic days (ED) 12−17, pregnant rats ate a choline-supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free (DEF) semisynthetic diet. Adult offspring either remained in standard housing or were given 21 daily visits to explore a maze. On the last ten exploration days, all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg). The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP rats compared to SFF or DEF rats. While maze experience increased the number of BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching experience did not alter cell proliferation in DEF rats. Similar patterns of cell proliferation were obtained with immunohistochemical staining for neuronal marker doublecortin, confirming that diet and exploration affected hippocampal neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We conclude that prenatal choline intake has enduring effects on adult hippocampal neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these alterations of neurogenesis may contribute to the mechanism of life-long changes in cognitive function governed by the availability of choline during gestation. PMID:17445242

  9. Adult neural precursor cells form connexin-dependent networks that improve their survival.

    PubMed

    Ravella, Ajaya; Ringstedt, Thomas; Brion, Jean-Pierre; Pandolfo, Massimo; Herlenius, Eric

    2015-10-21

    Establishment of cellular networks and calcium homeostasis are essential for embryonic stem cell proliferation and differentiation. We also hypothesized that adult neural progenitor cells form functional cellular networks relevant for their development. We isolated neuronal progenitor cells from the subventricular zone of 5-week-old mice to investigate the role of gap junctions, calcium homeostasis, and cellular networks in cell differentiation and survival. Western blotting and reverse transcription-PCR showed that the cells expressed the gap junction components connexin 26, 36, 43, and 45, and that expression of connexin 43 increased in early (8 days) differentiated cells. Transmission electron microscopy and immunocytochemistry also indicated that gap junctions were present. Scrape-loading experiments showed dye transfer between cells that could be prevented by gapjunction blockers; thus, functional intercellular gap junctions had been established. However, dye transfer was four times stronger in differentiated cultures, correlating with the increased connexin 43 expression. During time-lapse calcium imaging, both differentiated and undifferentiated cultures showed spontaneous calcium activity that was reduced by gap junction blockers. Cross-correlation analysis of the calcium recordings showed that the cells were interconnected through gap junctions and that the early-differentiated cells were organized in small-world networks. Gap junction blockers did not affect proliferation and differentiation, but resulted in twice as many apoptotic cells. mRNAi knockdown of connexin 43 also doubled the number of apoptotic cells. We conclude that adult neural progenitor cells form networks in vitro that are strengthened during early differentiation by increased expression of connexin 43. The networks are functional and improve cell survival. PMID:26351758

  10. Graft of a Tissue-Engineered Neural Scaffold Serves as a Promising Strategy to Restore Myelination after Rat Spinal Cord Transection

    PubMed Central

    Lai, Bi-Qin; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang

    2014-01-01

    Remyelination remains a challenging issue in spinal cord injury (SCI). In the present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs) with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS) scaffold. This was aimed to generate a tissue-engineered neural scaffold and to investigate whether it could enhance myelination after a complete T10 spinal cord transection in adult rats. Indeed, many NT-3 overexpressing SCs (NT-3-SCs) in the GS scaffold assumed the formation of myelin. More strikingly, a higher incidence of NSCs overexpressing TrkC differentiating toward myelinating cells was induced by NT-3-SCs. By transmission electron microscopy, the myelin sheath showed distinct multilayered lamellae formed by the seeded cells. Eighth week after the scaffold was transplanted, some myelin basic protein (MBP)-positive processes were observed within the transplantation area. Remarkably, certain segments of myelin derived from NSC-derived myelinating cells and NT-3-SCs were found to ensheath axons. In conclusion, we show here that transplantation of the GS scaffold promotes exogenous NSC-derived myelinating cells and SCs to form myelins in the injury/transplantation area of spinal cord. These findings thus provide a neurohistological basis for the future application or transplantation using GS neural scaffold to repair SCI. PMID:24325427

  11. Neural Coding of Reward Magnitude in the Orbitofrontal Cortex of the Rat during a Five-Odor Olfactory Discrimination Task

    ERIC Educational Resources Information Center

    van Duuren, Esther; Nieto Escamez, Francisco A.; Joosten, Ruud N. J. M. A.; Visser, Rein; Mulder, Antonius B.; Pennartz, Cyriel M. A.

    2007-01-01

    The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory…

  12. STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats*

    PubMed Central

    Tang, Qing-ping; Shen, Qin; Wu, Li-xiang; Feng, Xiang-ling; Liu, Hui; Wu, Bei; Huang, Xiao-song; Wang, Gai-qing; Li, Zhong-hao; Liu, Zun-jing

    2016-01-01

    Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes. PMID:27381726

  13. STAT3 signal that mediates the neural plasticity is involved in willed-movement training in focal ischemic rats.

    PubMed

    Tang, Qing-Ping; Shen, Qin; Wu, Li-Xiang; Feng, Xiang-Ling; Liu, Hui; Wu, Bei; Huang, Xiao-Song; Wang, Gai-Qing; Li, Zhong-Hao; Liu, Zun-Jing

    2016-07-01

    Willed-movement training has been demonstrated to be a promising approach to increase motor performance and neural plasticity in ischemic rats. However, little is known regarding the molecular signals that are involved in neural plasticity following willed-movement training. To investigate the potential signals related to neural plasticity following willed-movement training, littermate rats were randomly assigned into three groups: middle cerebral artery occlusion, environmental modification, and willed-movement training. The infarct volume was measured 18 d after occlusion of the right middle cerebral artery. Reverse transcription-polymerase chain reaction (PCR) and immunofluorescence staining were used to detect the changes in the signal transducer and activator of transcription 3 (STAT3) mRNA and protein, respectively. A chromatin immunoprecipitation was used to investigate whether STAT3 bound to plasticity-related genes, such as brain-derived neurotrophic factor (BDNF), synaptophysin, and protein interacting with C kinase 1 (PICK1). In this study, we demonstrated that STAT3 mRNA and protein were markedly increased following 15-d willed-movement training in the ischemic hemispheres of the treated rats. STAT3 bound to BDNF, PICK1, and synaptophysin promoters in the neocortical cells of rats. These data suggest that the increased STAT3 levels after willed-movement training might play critical roles in the neural plasticity by directly regulating plasticity-related genes. PMID:27381726

  14. Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury

    PubMed Central

    Shin, Kyungha; Cha, Yeseul; Kim, Kwang Sei; Choi, Ehn-Kyoung; Choi, Youngjin; Guo, Haiyu; Ban, Young-Hwan; Kim, Jong-Choon; Park, Dongsun; Kim, Yun-Bae

    2016-01-01

    Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs) overexpressing choline acetyltransferase (ChAT) improve cognitive function of Alzheimer's disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh) level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA) in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing) time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level. PMID:27087745

  15. Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury.

    PubMed

    Shin, Kyungha; Cha, Yeseul; Kim, Kwang Sei; Choi, Ehn-Kyoung; Choi, Youngjin; Guo, Haiyu; Ban, Young-Hwan; Kim, Jong-Choon; Park, Dongsun; Kim, Yun-Bae

    2016-01-01

    Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs) overexpressing choline acetyltransferase (ChAT) improve cognitive function of Alzheimer's disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh) level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA) in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing) time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level. PMID:27087745

  16. Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer's Disease Rat Models

    PubMed Central

    Haiyan, Hu; Rensong, Yang; Guoqin, Jin; Xueli, Zhang; Huaying, Xia; Yanwu, Xu

    2016-01-01

    Stem cell-based therapy is a promising treatment strategy for neurodegenerative diseases such as Alzheimer's disease (AD). However, the mechanism underlying the maintenance of renewal and replacement capabilities of endogenous progenitor cells or engrafted stem cells in a pathological environment remains elusive. To investigate the effect of astragaloside IV (ASI) on the proliferation and differentiation of the engrafted neural stem cells (NSCs), we cultured NSCs from the hippocampus of E14 rat embryos, treated the cells with ASI, and then transplanted the cells into the hippocampus of rat AD models. In vitro experimentation showed that 10−5 M ASI induced NSCs to differentiate into β-tubulin III+ and GFAP+ cells. NSCs transplantation into rat AD models resulted in improvements in learning and memory, especially in the ASI-treated groups. ASI treatment resulted in an increase in the number of β-tubulin III+ cells in the hippocampus. Further investigation showed that ASI inhibited PS1 expression in vitro and in vivo. The high-dose ASI downregulated the Notch intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In conclusion, ASI treatment resulted in improvements in learning and memory of AD models by promoting NSC proliferation and differentiation partly through the Notch signal pathway. PMID:27034688

  17. Different sensitivity of PPARalpha gene expression to nutritional changes in liver of suckling and adult rats.

    PubMed

    Panadero, Maribel; Herrera, Emilio; Bocos, Carlos

    2005-01-14

    The amount of peroxisome proliferator-activated receptor-alpha (PPARalpha) protein was markedly augmented in the liver of suckling rats compared to adult rats. This different PPARalpha abundance was used to study the sensitivity to nutritional changes in the expression and activity of this receptor. Thus, 10-day-old and adult rats were orally given either glucose, Intralipid or a combination of both diets, and liver mRNA levels of PPARalpha and the PPAR related genes, acyl-CoA oxidase (ACO) and phosphoenolpyruvate carboxykinase (PEPCK), and plasma metabolites were measured. In neonates, the expression of PPARalpha and ACO was seen to increase when the level of FFA in plasma was also high, unless an elevated level of insulin was also present. However, this fatty acid-induced effect was not detected in adult rats. On the contrary, the hepatic expression of PEPCK was modulated by the nutritional changes similarly in both neonates and adult rats. Thus, it may be concluded that the expression of the PPARalpha gene in adult rats seems to be less sensitive to nutritional changes than in neonates. PMID:15607334

  18. Neural correlates of training and transfer effects in working memory in older adults.

    PubMed

    Heinzel, Stephan; Lorenz, Robert C; Pelz, Patricia; Heinz, Andreas; Walter, Henrik; Kathmann, Norbert; Rapp, Michael A; Stelzel, Christine

    2016-07-01

    As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12sessions (45min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks

  19. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

    PubMed Central

    Wang, Hua; Lau, Benson Wui-Man; Wang, Ning-li; Wang, Si-ying; Lu, Qing-jun; Chang, Raymond Chuen-Chung; So, Kwok-fai

    2015-01-01

    Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype. PMID:26889185

  20. Acupuncture Induces the Proliferation and Differentiation of Endogenous Neural Stem Cells in Rats with Traumatic Brain Injury

    PubMed Central

    Jiang, Shuting; Chen, Weihao; Zhang, Yimin; Zhang, Yujuan; Chen, Ailian; Dai, Qiufu; Lin, Shujun; Lin, Hanyu

    2016-01-01

    Purpose. To investigate whether acupuncture induced the proliferation and differentiation of endogenous neural stem cells (NSCs) in a rat model of traumatic brain injury (TBI). Methods. 104 Sprague-Dawley rats were randomly divided into normal, model, and acupuncture groups. Each group was subdivided into three-day (3 d), seven-day (7 d), and fourteen-day (14 d) groups. The rat TBI model was established using Feeney's freefall epidural impact method. The rats in the acupuncture group were treated at acupoints (Baihui, Shuigou, Fengfu, Yamen, and bilateral Hegu). The normal and model groups did not receive acupuncture. The establishment of the rat TBI model and the therapeutic effect of acupuncture were assessed using neurobehavioral scoring and hematoxylin-eosin staining. The proliferation and differentiation of NSCs in TBI rats were analyzed using immunofluorescence microscopy. Results. The levels of nestin-expressing cells and bromodeoxyuridine/glial fibrillary acidic protein- (BrdU/GFAP-) and BrdU/S100 calcium-binding protein B-positive and BrdU/microtubule-associated protein 2- and BrdU/galactocerebrosidase-positive cells were more significantly increased at various time points in the acupuncture group than in the model group (P < 0.01), except for a decreased level of BrdU/GFAP-positive cells at 7 d and 14 d. Conclusion. Acupuncture induced the proliferation and differentiation of NSCs, thereby promoting neural repair in the TBI rats. PMID:27313641

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

    PubMed Central

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

    2014-01-01

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

  2. Differential expression of id genes and their potential regulator znf238 in zebrafish adult neural progenitor cells and neurons suggests distinct functions in adult neurogenesis.

    PubMed

    Diotel, Nicolas; Beil, Tanja; Strähle, Uwe; Rastegar, Sepand

    2015-01-01

    Teleost fish display a remarkable ability to generate new neurons and to repair brain lesions during adulthood. They are, therefore, a very popular model to investigate the molecular mechanisms of constitutive and induced neurogenesis in adult vertebrates. In this study, we investigated the expression patterns of inhibitor of DNA binding (id) genes and of their potential transcriptional repressor, znf238, in the whole brain of adult zebrafish. We show that while id1 is exclusively expressed in ventricular cells in the whole brain, id2a, id3 and id4 genes are expressed in broader areas. Interestingly, znf238 was also detected in these regions, its expression overlapping with id2a, id3 and id4 expression. Further detailed characterization of the id-expressing cells demonstrated that (a) id1 is expressed in type 1 and type 2 neural progenitors as previously published, (b) id2a in type 1, 2 and 3 neural progenitors, (c) id3 in type 3 neural progenitors and (d) id4 in postmitotic neurons. Our data provide a detailed map of id and znf238 expression in the brain of adult zebrafish, supplying a framework for studies of id genes function during adult neurogenesis and brain regeneration in the zebrafish. PMID:26107416

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

    PubMed Central

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

    2000-01-01

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

  4. Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging

    PubMed Central

    Stein, Liana R; Imai, Shin-ichiro

    2014-01-01

    Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain unclear. Here, we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical in oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon insult. These phenotypes recapitulate defects in NSPCs during aging, giving rise to the possibility that Nampt-mediated NAD+ biosynthesis is a mediator of age-associated functional declines in NSPCs. PMID:24811750

  5. Adult neural stem cell behavior underlying constitutive and restorative neurogenesis in zebrafish.

    PubMed

    Barbosa, Joana S; Ninkovic, Jovica

    2016-01-01

    Adult Neural Stem Cells (aNSCs) generate new neurons that integrate into the pre-existing networks in specific locations of the Vertebrate brain. Moreover, aNSCs contribute with new neurons to brain regeneration in some non-mammalian Vertebrates. The similarities and the differences in the cellular and molecular processes governing neurogenesis in the intact and regenerating brain are still to be assessed. Toward this end, we recently established a protocol for non-invasive imaging of aNSC behavior in their niche in vivo in the adult intact and regenerating zebrafish telencephalon. We observed different modes of aNSC division in the intact brain and a novel mode of neurogenesis by direct conversion, which contributes to stem cell depletion with age. After injury, the generation of neurons is increased both by the activation of additional aNSCs and a shift in the division mode of aNSCs, thereby contributing to the successful neuronal regeneration. The cellular behavior we observed opens new questions regarding long-term aNSC maintenance in homeostasis and in regeneration. In this commentary we discuss our data and new questions arising in the context of aNSC behavior, not only in zebrafish but also in other species, including mammals. PMID:27606336

  6. Behavioral and Neural Substrates of Habit Formation in Rats Intravenously Self-Administering Nicotine

    PubMed Central

    Clemens, Kelly J; Castino, Matthew R; Cornish, Jennifer L; Goodchild, Ann K; Holmes, Nathan M

    2014-01-01

    Tobacco addiction involves a transition from occasional, voluntary smoking towards habitual behavior that becomes increasingly resistant to quitting. The development of smoking habits may reflect a loss of behavioral control that can be modeled in rats. This study investigated the behavioral and neural substrates of habit formation in rats exposed to either brief (10 days) or extended (47 days) intravenous (IV) nicotine self-administration training. Following training, the first cohort of rats were exposed to a nicotine devaluation treatment, which involved repeated pairings of IV nicotine with lithium injection. They were then tested for sensitivity of responding to nicotine devaluation under extinction and reinstatement conditions. The second cohort of rats received equivalent self-administration training followed by processing of brain tissue for c-Fos immunohistochemistry. After brief training, devaluation suppressed nicotine-seeking during tests of extinction and reinstatement, confirming that responding is initially sensitive to current nicotine value, and therefore, goal directed. In contrast, after extended training, devaluation had no effect on extinction or reinstatement of responding, indicating that responding had become habitual. Complementary neuroanalysis revealed that extended nicotine self-administration was associated with increased c-Fos expression in brain regions implicated in habitual control of reward seeking, including activation of the dorsolateral striatum and substantia nigra pars compacta. These findings provide evidence of direct devaluation of an IV drug reward, that nicotine self-administration is initially goal-directed but becomes habitual with extended training, and that this behavioral transition involves activation of brain areas associated with the nigrostriatal system. PMID:24823947

  7. Exposure to social defeat stress in adolescence improves the working memory and anxiety-like behavior of adult female rats with intrauterine growth restriction, independently of hippocampal neurogenesis.

    PubMed

    Furuta, Miyako; Ninomiya-Baba, Midori; Chiba, Shuichi; Funabashi, Toshiya; Akema, Tatsuo; Kunugi, Hiroshi

    2015-04-01

    Intrauterine growth restriction (IUGR) is a risk factor for memory impairment and emotional disturbance during growth and adulthood. However, this risk might be modulated by environmental factors during development. Here we examined whether exposing adolescent male and female rats with thromboxane A2-induced IUGR to social defeat stress (SDS) affected their working memory and anxiety-like behavior in adulthood. We also used BrdU staining to investigate hippocampal cellular proliferation and BrdU and NeuN double staining to investigate neural differentiation in female IUGR rats. In the absence of adolescent stress, IUGR female rats, but not male rats, scored significantly lower in the T-maze test of working memory and exhibited higher anxiety-like behavior in the elevated-plus maze test compared with controls. Adolescent exposure to SDS abolished these behavioral impairments in IUGR females. In the absence of adolescent stress, hippocampal cellular proliferation was significantly higher in IUGR females than in non-IUGR female controls and was not influenced by adolescent exposure to SDS. Hippocampal neural differentiation was equivalent in non-stressed control and IUGR females. Neural differentiation was significantly increased by adolescent exposure to SDS in controls but not in IUGR females. There was no significant difference in the serum corticosterone concentrations between non-stressed control and IUGR females; however, adolescent exposure to SDS significantly increased serum corticosterone concentration in control females but not in IUGR females. These results demonstrate that adolescent exposure to SDS improves behavioral impairment independent of hippocampal neurogenesis in adult rats with IUGR. PMID:25725425

  8. Effects of psychostimulants on social interaction in adult male rats.

    PubMed

    Šlamberová, Romana; Mikulecká, Anna; Macúchová, Eva; Hrebíčková, Ivana; Ševčíková, Mária; Nohejlová, Kateryna; Pometlová, Marie

    2015-12-01

    Psychostimulants are known to have a huge impact on different forms of social behaviour. The aim of the present study was to compare the effects of three different psychostimulants [amphetamine, cocaine and 3,4 methylenedimethoxyamphetamine (MDMA)] on social interaction (SI) in adult male rats. The SI test was performed in a familiar arena and under low-stress environmental conditions. Experimental animals received amphetamine (0.5, 1.0, 1.5 mg/kg), cocaine (0.5, 1.0, 1.5, 2.5, 5.0, 10.0 mg/kg) or MDMA (2.5, 5.0, 10 mg/kg) and control animals received saline (1 ml/kg) 45 min before the SI test. Time spent in SI (individual patterns of social behaviour) and nonsocial activities (locomotion and rearing) were video recorded and then analysed offline, with the following results: (a) all doses of amphetamine decreased SI. Specifically, all doses of amphetamine decreased mutual sniffing, and the higher doses also decreased allo-grooming and following behaviours. (b) The higher doses of cocaine decreased SI, especially mutual sniffing, allo-grooming and climbing over. Cocaine at the dose of 5.0 mg/kg increased genital investigation compared with lower doses. (c) All doses of MDMA decreased mutual sniffing and climbing over; the two higher doses decreased allo-grooming behaviour, and only the highest dose decreased following. The two higher doses of amphetamine and all the doses of MDMA increased locomotion and rearing; cocaine did not affect locomotion, but increased rearing at higher doses. In conclusion, the results confirm the well-known finding that psychostimulants suppress SI, but also show novel differences in the effects of psychostimulants on specific patterns of SI. PMID:26061354

  9. Safety of Intracerebroventricular Copper Histidine in Adult Rats

    PubMed Central

    Lem, Kristen E.; Brinster, Lauren R.; Tjurmina, Olga; Lizak, Martin; Lal, Simina; Centeno, Jose A.; Liu, Po-Ching; Godwin, Sarah C.; Kaler, Stephen G.

    2007-01-01

    Classical Menkes disease is an X-linked recessive neurodegenerative disorder caused by mutations in a P-type ATPase (ATP7A) that normally delivers copper to the developing central nervous system. Infants with large deletions, or other mutations in ATP7A that incapacitate copper transport to the brain, show poor clinical outcomes and subnormal brain copper despite early subcutaneous copper histidine (CuHis) injections. These findings suggest a need for direct central nervous system approaches in such patients. To begin to evaluate an aggressive but potentially useful new strategy for metabolic improvement of this disorder, we studied the acute and chronic effects of CuHis administered by intracerebroventricular (ICV) injection in healthy adult rats. Magnetic resonance imaging (MRI) after ICV CuHis showed diffuse T1-signal enhancement, indicating wide brain distribution of copper after ICV administration, and implying the utility of this paramagnetic metal as a MRI contrast agent. The maximum tolerated dose (MTD) of CuHis, defined as the highest dose that did not induce overt toxicity, growth retardation, or reduce lifespan, was 0.5 mcg. Animals receiving multiple infusions of this MTD showed increased brain copper concentrations, but no significant differences in activity, behavior, and somatic growth, or brain histology compared to saline-injected controls. Based on estimates of the brain copper deficit in Menkes disease patients, CuHis doses 10-fold lower than the MTD found in this study may restore proper brain copper concentration. Our results suggest that ICV CuHis administration have potential as a novel treatment approach in Menkes disease infants with severe mutations. Future trials of direct CNS copper administration in mouse models of Menkes disease will be informative. PMID:17336116

  10. Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors

    PubMed Central

    Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H.; Law, Ping-Yee

    2016-01-01

    The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine’s inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3–28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1. PMID:27078155

  11. Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors.

    PubMed

    Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H; Law, Ping-Yee

    2016-01-01

    The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine's inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3-28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1. PMID:27078155

  12. Does 5-Bromo-2′-deoxyuridine (BrdU) Disrupt Cell Proliferation and Neuronal Maturation in the Adult Rat Hippocampus In Vivo?

    PubMed Central

    Hancock, Aneeka; Priester, Carolina; Kidder, Emily; Keith, Julian R.

    2014-01-01

    5-Bromo-2′-deoxyuridine (BrdU) is frequently used as a mitotic marker in studies of cell proliferation. Recent studies have reported cytotoxic effects of BrdU on neural progenitor cells in embryonic and neonatal brains in vivo and in adult tissue studied in vitro. The present study was conducted to assess whether BrdU interferes with cell proliferation and neuronal maturation in the rat adult hippocampus in vivo. BrdU effects across a wide range of doses (40 – 480 mg/kg) on cell proliferation and the population of immature neurons in the adult hippocampus were investigated using immunohistochemical labeling methods for the cell cycle marker Ki67 and a marker for immature neurons, doublecortin. BrdU did not influence cell proliferation in the dentate gyrus or the population of immature neurons observed in the adult hippocampus relative to those observed in saline treated controls. Thus, in contrast with reports of deleterious effects of BrdU in embryonic and neonatal tissue and adult tissue studied in vitro, BrdU does not appear to have cytotoxic effects on proliferating hippocampal cells or immature neurons in vivo in rats. PMID:19121338

  13. Does 5-bromo-2'-deoxyuridine (BrdU) disrupt cell proliferation and neuronal maturation in the adult rat hippocampus in vivo?

    PubMed

    Hancock, Aneeka; Priester, Carolina; Kidder, Emily; Keith, Julian R

    2009-05-16

    5-Bromo-2'-deoxyuridine (BrdU) is frequently used as a mitotic marker in studies of cell proliferation. Recent studies have reported cytotoxic effects of BrdU on neural progenitor cells in embryonic and neonatal brains in vivo and in adult tissue studied in vitro. The present study was conducted to assess whether BrdU interferes with cell proliferation and neuronal maturation in the rat adult hippocampus in vivo. BrdU effects across a wide range of doses (40-480 mg/kg) on cell proliferation and the population of immature neurons in the adult hippocampus were investigated using immunohistochemical labeling methods for the cell cycle marker Ki67 and a marker for immature neurons, doublecortin. BrdU did not influence cell proliferation in the dentate gyrus or the population of immature neurons observed in the adult hippocampus relative to those observed in saline treated controls. Thus, in contrast with reports of deleterious effects of BrdU in embryonic and neonatal tissue and adult tissue studied in vitro, BrdU does not appear to have cytotoxic effects on proliferating hippocampal cells or immature neurons in vivo in rats. PMID:19121338

  14. Comprehensive Locomotor Outcomes Correlate to Hyperacute Diffusion Tensor Measures After Spinal Cord Injury in the Adult Rat

    PubMed Central

    Kim, Joong; Song, Sheng-Kwei; Burke, Darlene A.; Magnuson, David S. K.

    2012-01-01

    In adult rats, locomotor deficits following a contusive thoracic spinal cord injury (SCI) are caused primarily by white matter loss/dysfunction at the epicenter. This loss/dysfunction decreases descending input from the brain and cervical spinal cord, and decreases ascending signals in long propriospinal, spinocerebellar and somatosensory pathways, among many others. Predicting the long-term functional consequences of a contusive injury acutely, without knowledge of the injury severity is difficult due to the temporary flaccid paralysis and loss of reflexes that accompanies spinal shock. It is now well known that recovery of high quality hindlimb stepping requires only 12-15% spared white matter at the epicenter, but that forelimb-hindlimb coordination and precision stepping (grid or horizontal ladder) requires substantially more trans-contusion communication. In order to translate our understanding of the neural substrates for functional recovery in the rat to the clinical arena, common outcome measures and imaging modalities are required. In the current study we furthered the exploration of one of these approaches, diffusion tensor magnetic resonance imaging (DTI), a technique now used commonly to image the brain in clinical research but rarely used diagnostically or prognostically for spinal cord injury. In the adult rat model of SCI, we found that hyper-acute (<3 hours post-injury) DTI of the lateral and ventral white matter at the injury epicenter was predictive of both electrophysiological and behavioral (locomotor) recovery at 4 weeks post-injury, despite the presence of flaccid paralysis/spinal shock. Regions of white matter with a minimum axial diffusivity of 1.5μm2/ms at 3 hours were able to conduct action potentials at 4 weeks, and axial diffusivity within the lateral funiculus was highly predictive of locomotor function at 4 weeks. These observations suggest that acute DTI should be useful to provide functional predictions for spared white matter

  15. Saturation thresholds of evoked neural and hemodynamic responses in awake and asleep rats

    NASA Astrophysics Data System (ADS)

    Schei, Jennifer L.; Van Nortwick, Amy S.; Meighan, Peter C.; Rector, David M.

    2011-03-01

    Neural activation generates a hemodynamic response to the localized region replenishing nutrients to the area. Changes in vigilance state have been shown to alter the vascular response where the vascular response is muted during wake compared to quiet sleep. We tested the saturation thresholds of the neurovascular response in the auditory cortex during wake and sleep by chronically implanting rats with an EEG electrode, a light emitting diode (LED, 600 nm), and photodiode to simultaneously measure evoked response potentials (ERPs) and evoked hemodynamic responses. We stimulated the cortex with a single speaker click delivered at random intervals 2-13 s at varied stimulus intensities ranging from 45-80 dB. To further test the potential for activity related saturation, we sleep deprived animals for 2, 4, or 6 hours and recorded evoked responses during the first hour recovery period. With increasing stimulus intensity, integrated ERPs and evoked hemodynamic responses increased; however the hemodynamic response approached saturation limits at a lower stimulus intensity than the ERP. With longer periods of sleep deprivation, the integrated ERPs did not change but evoked hemodynamic responses decreased. There may be physical limits in cortical blood delivery and vascular compliance, and with extended periods of neural activity during wake, vessels may approach these limits.

  16. The effects of Nigella sativa on neural damage after pentylenetetrazole induced seizures in rats.

    PubMed

    Seghatoleslam, Masoumeh; Alipour, Fatemeh; Shafieian, Reihaneh; Hassanzadeh, Zahra; Edalatmanesh, Mohammad Amin; Sadeghnia, Hamid Reza; Hosseini, Mahmoud

    2016-07-01

    Nigella sativa (NS) has been suggested to have neuroprotective and anti-seizures properties. The aim of current study was to investigate the effects of NS hydro-alcoholic extract on neural damage after pentylenetetrazole (PTZ) - induced repeated seizures. The rats were divided into five groups: (1) control (saline), (2) PTZ (50 mg/kg, i.p.), (3-5) PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 (100, 200 and 400 mg/kg of NS extract respectively, 30 min prior to each PTZ injection on 5 consecutive days). The passive avoidance (PA) test was done and the brains were then removed for histological measurements. The PTZ-NS 100, PTZ-NS 200 and PTZ-NS 400 groups had lower seizure scores than PTZ group (P < 0.01 and P < 0.001). The latency to enter the dark compartment by the animals of PTZ group was lower than control in PA test (P < 0.01). Pre-treatment by 400 mg/kg of the extract increased the latency to enter the dark compartment (P < 0.05). Meanwhile, different doses of the extract inhibited production of dark neurons in different regions of hippocampus (P < 0.001). The present study allows us to suggest that the NS possesses a potential ability to prevent hippocampal neural damage which is accompanied with improving effects on memory. PMID:27419091

  17. Increased proliferation and gliogenesis of cultured rat neural progenitor cells by lipopolysaccharide-stimulated astrocytes.

    PubMed

    Go, Hyo Sang; Shin, Chan Young; Lee, Sung Hoon; Jeon, Se-Jin; Kim, Ki Chan; Choi, Chang Soon; Ko, Kwang Ho

    2009-01-01

    Neural progenitor cells (NPC) are self-renewing multipotent cells that generate neurons and glial cells in the brain. NPCs generate neurons and glia not only during development but also after neural injury. Recent studies have shown that endogenous NPCs are activated after brain injury and migrate toward damaged areas where astrocyte activation occurs. Considering the massive proliferation of astrocytes as well as the production of several kinds of cytoactive molecules after brain injury, such as NO, growth factors and cytokines, it is tempting to think that cytoactive molecules released by activated glial cells regulate neural progenitor differentiation and proliferation through inflammatory mediators. To test this hypothesis, we stimulated rat primary astrocytes with lipopolysaccharide (LPS) to induce the activation of astrocytes. After addition of the conditioned media from LPS-stimulated astrocytes to NPC culture, proliferation was examined by MTT assay and bromodeoxyuridine (BrdU) incorporation. The differentiation of NPC into neurons and astrocytes was examined by Western blot, ELISA and immunocytochemical staining with cell-type-specific markers. Conditioned media from LPS-stimulated astrocytes increased NPC proliferation as well as gliogenesis as compared with control conditioned media from astrocytes without LPS stimulation. In contrast, neurogenesis was decreased by LPS-conditioned media. To investigate the molecular mechanism mediating glial differentiation and proliferation of NPC by reactive astrocytes, we added inhibitors of the Erk and JNK pathways during LPS stimulation. These inhibitors - except for a p38 inhibitor - decreased NPC proliferation and glial differentiation. These results suggest that LPS stimulated astrocytes generate factors regulating NPC proliferation and gliogenesis via the Erk and JNK pathways. PMID:19609085

  18. Electrophysiological study of infant and adult rats under acute intoxication with fluoroacetamide.

    PubMed

    Kuznetsov, Sergey V; Jenkins, Richard O; Goncharov, Nikolay V

    2007-01-01

    A study was conducted of acute intoxication of infant and adult Wistar rats with fluoroacetamide (FAA), an inhibitor of oxidative metabolism. FAA was administered orally to adult rats at 1/2 LD(50) and subcutaneously to infant rats at LD(100) or 1/10 LD(50). Electrocardiogram (ECG), respiration and motor activity were registered for 7 days. Clinical analysis of ECG and the heart rate variability (HRV) was carried out to assess the state of the vegetative nervous system. In adult rats, FAA caused marked disturbances in the activity of cardiovascular and respiratory systems, including the development of a potentially lethal acute cor pulmonale. Conversely, there were no significant changes of cardiac function and respiration in infant rats; they died because of extreme emaciation accompanied by retardation of development. In adult rats, bursts of associated cardiac and respiratory tachyarrhythmia, as well as regular high amplitude spasmodic sighs having a deca-second rhythm were observed. In both infant and adult rats, FAA caused short-term enhancement of humoral (metabolic) and sympathetic activities, followed by a gradual and stable predominance of parasympathetic influence on HRV. Under conditions of FAA inhibition of the tricarboxylic acid cycle, the observed physiological reactions may be explained by activation of alternative metabolic pathways. This is also supported by a lack of ontogenetically caused inhibition of spontaneous motor activity in infant rats poisoned with FAA, which highlights the significance of the alternative metabolic pathways for implementation of deca-second and minute rhythms and a lack of a rigid dependence of these rhythms upon activity of neuronal networks. PMID:17351914

  19. An fMRI comparison of neural activity associated with recognition of familiar melodies in younger and older adults

    PubMed Central

    Sikka, Ritu; Cuddy, Lola L.; Johnsrude, Ingrid S.; Vanstone, Ashley D.

    2015-01-01

    Several studies of semantic memory in non-musical domains involving recognition of items from long-term memory have shown an age-related shift from the medial temporal lobe structures to the frontal lobe. However, the effects of aging on musical semantic memory remain unexamined. We compared activation associated with recognition of familiar melodies in younger and older adults. Recognition follows successful retrieval from the musical lexicon that comprises a lifetime of learned musical phrases. We used the sparse-sampling technique in fMRI to determine the neural correlates of melody recognition by comparing activation when listening to familiar vs. unfamiliar melodies, and to identify age differences. Recognition-related cortical activation was detected in the right superior temporal, bilateral inferior and superior frontal, left middle orbitofrontal, bilateral precentral, and left supramarginal gyri. Region-of-interest analysis showed greater activation for younger adults in the left superior temporal gyrus and for older adults in the left superior frontal, left angular, and bilateral superior parietal regions. Our study provides powerful evidence for these musical memory networks due to a large sample (N = 40) that includes older adults. This study is the first to investigate the neural basis of melody recognition in older adults and to compare the findings to younger adults. PMID:26500480

  20. An fMRI comparison of neural activity associated with recognition of familiar melodies in younger and older adults.

    PubMed

    Sikka, Ritu; Cuddy, Lola L; Johnsrude, Ingrid S; Vanstone, Ashley D

    2015-01-01

    Several studies of semantic memory in non-musical domains involving recognition of items from long-term memory have shown an age-related shift from the medial temporal lobe structures to the frontal lobe. However, the effects of aging on musical semantic memory remain unexamined. We compared activation associated with recognition of familiar melodies in younger and older adults. Recognition follows successful retrieval from the musical lexicon that comprises a lifetime of learned musical phrases. We used the sparse-sampling technique in fMRI to determine the neural correlates of melody recognition by comparing activation when listening to familiar vs. unfamiliar melodies, and to identify age differences. Recognition-related cortical activation was detected in the right superior temporal, bilateral inferior and superior frontal, left middle orbitofrontal, bilateral precentral, and left supramarginal gyri. Region-of-interest analysis showed greater activation for younger adults in the left superior temporal gyrus and for older adults in the left superior frontal, left angular, and bilateral superior parietal regions. Our study provides powerful evidence for these musical memory networks due to a large sample (N = 40) that includes older adults. This study is the first to investigate the neural basis of melody recognition in older adults and to compare the findings to younger adults. PMID:26500480

  1. Long-Term Survival of Photoreceptors Transplanted into the Adult Murine Neural Retina Requires Immune Modulation

    PubMed Central

    West, Emma L.; Pearson, Rachael A.; Barker, Susie E.; Luhmann, Ulrich F. O.; Maclaren, Robert E.; Barber, Amanda C.; Duran, Yanai; Smith, Alexander J.; Sowden, Jane C.; Ali, Robin R.

    2012-01-01

    Stem cell therapy presents an opportunity to replace photoreceptors that are lost as a result of inherited and age-related degenerative disease. We have previously shown that murine postmitotic rod photoreceptor precursor cells, identified by expression of the rod-specific transcription factor Nrl, are able to migrate into and integrate within the adult murine neural retina. However, their long-term survival has yet to be determined. Here, we found that integrated Nrl.gfp+ve photoreceptors were present up to 12 months post-transplantation, albeit in significantly reduced numbers. Surviving cells had rod-like morphology, including inner/outer segments and spherule synapses. In a minority of eyes, we observed an early, marked reduction in integrated photoreceptors within 1 month post-transplantation, which correlated with increased numbers of amoeboid macrophages, indicating acute loss of transplanted cells due to an inflammatory response. In the majority of transplants, similar numbers of integrated cells were observed between 1 and 2 months post-transplantation. By 4 months, however, we observed a significant decrease in integrated cell survival. Macrophages and T cells were present around the transplantation site, indicating a chronic immune response. Immune suppression of recipients significantly increased transplanted photoreceptor survival, indicating that the loss observed in unsuppressed recipients resulted from T cell-mediated host immune responses. Thus, if immune responses are modulated, correctly integrated transplanted photoreceptors can survive for extended periods of time in hosts with partially mismatched H-2 haplotypes. These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective. PMID:20857496

  2. Development Switch in Neural Circuitry Underlying Odor-Malaise Learning

    ERIC Educational Resources Information Center

    Lunday, Lauren; Miner, Cathrine; Roth, Tania L.; Sullivan, Regina M.; Shionoya, Kiseko; Moriceau, Stephanie

    2006-01-01

    Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and…

  3. Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

    PubMed Central

    Amrein, Irmgard; Becker, Anton S.; Engler, Stefanie; Huang, Shih-hui; Müller, Julian; Slomianka, Lutz; Oosthuizen, Maria K.

    2014-01-01

    African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape mole-rats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents. PMID

  4. Adolescent alcohol exposure decreased sensitivity to nicotine in adult Wistar rats.

    PubMed

    Boutros, Nathalie; Semenova, Svetlana; Markou, Athina

    2016-07-01

    Many adolescents engage in heavy alcohol use. Limited research in humans indicates that adolescent alcohol use predicts adult tobacco use. The present study investigated whether adolescent intermittent ethanol (AIE) exposure alters nicotine sensitivity in adulthood. Adolescent male Wistar rats (postnatal day 28-53) were exposed to AIE exposure that consisted of 5 g/kg of 25 percent ethanol three times per day in a 2 days on/2 days off regimen. Control rats received water with the same exposure regimen. In adulthood, separate groups of rats were tested for nicotine intravenous self-administration (IVSA), drug discrimination and conditioned taste aversion (CTA). The dose-response function for nicotine IVSA under a fixed-ratio schedule of reinforcement was similar in AIE-exposed and control rats. However, AIE-exposed rats self-administered less nicotine at the lowest dose, suggesting that low-dose nicotine was less reinforcing in AIE-exposed, compared with control rats. AIE-exposed rats self-administered less nicotine under a progressive-ratio schedule, suggesting decreased motivation for nicotine after AIE exposure. The discriminative stimulus effects of nicotine were diminished in AIE-exposed rats compared with control rats. No group differences in nicotine CTA were observed, suggesting that AIE exposure had no effect on the aversive properties of nicotine. Altogether, these results demonstrate that AIE exposure decreases sensitivity to the reinforcing, motivational and discriminative properties of nicotine while leaving the aversive properties of nicotine unaltered in adult rats. These findings suggest that drinking during adolescence may result in decreased sensitivity to nicotine in adult humans, which may in turn contribute to the higher rates of tobacco smoking. PMID:25950618

  5. Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure.

    PubMed

    Fernandez, Gina M; Stewart, William N; Savage, Lisa M

    2016-01-01

    Previous research has found that adolescent ethanol (EtOH) exposure alters drug seeking behaviors, cognition and neuroplasticity. Using male Sprague Dawley rats, differences in spatial working memory, non-spatial discrimination learning and behavioral flexibility were explored as a function of age at the onset (mid-adolescent vs. adult) of chronic EtOH exposure (CET). Concentrations of mature brain-derived neurotrophic factor (mBDNF) and beta-nerve growth factor (β-NGF) in the prefrontal cortex and hippocampus were also assessed at different time-points: during CET, following acute abstinence (48-hrs), and after protracted abstinence (6-8 wks). Our results revealed that an adolescent onset of CET leads to increased EtOH consumption that persisted into adulthood. In both adult and adolescent onset CET groups, there were significant long-term reductions in prefrontal cortical mBDNF and β-NGF levels. However, only adult onset CET rats displayed decreased hippocampal BDNF levels. Spatial memory, assessed by spontaneous alternation and delayed alternation, was not significantly affected by CET as a function of age of drinking onset, but higher blood-EtOH levels were correlated with lower spontaneous alternation scores. Regardless of the age of onset, EtOH exposed rats were impaired on non-spatial discrimination learning and displayed inflexible behavioral patterns upon reversal learning. Our results indicate that adolescent EtOH exposure changes long-term consumption patterns producing behavioral and neural dysfunctions that persist across the lifespan. PMID:26930631

  6. Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure

    PubMed Central

    Fernandez, Gina M.; Stewart, William N.; Savage, Lisa M.

    2016-01-01

    Previous research has found that adolescent ethanol (EtOH) exposure alters drug seeking behaviors, cognition and neuroplasticity. Using male Sprague Dawley rats, differences in spatial working memory, non-spatial discrimination learning and behavioral flexibility were explored as a function of age at the onset (mid-adolescent vs. adult) of chronic EtOH exposure (CET). Concentrations of mature brain-derived neurotrophic factor (mBDNF) and beta-nerve growth factor (β-NGF) in the prefrontal cortex and hippocampus were also assessed at different time-points: during CET, following acute abstinence (48-hrs), and after protracted abstinence (6–8 wks). Our results revealed that an adolescent onset of CET leads to increased EtOH consumption that persisted into adulthood. In both adult and adolescent onset CET groups, there were significant long-term reductions in prefrontal cortical mBDNF and β-NGF levels. However, only adult onset CET rats displayed decreased hippocampal BDNF levels. Spatial memory, assessed by spontaneous alternation and delayed alternation, was not significantly affected by CET as a function of age of drinking onset, but higher blood–EtOH levels were correlated with lower spontaneous alternation scores. Regardless of the age of onset, EtOH exposed rats were impaired on non-spatial discrimination learning and displayed inflexible behavioral patterns upon reversal learning. Our results indicate that adolescent EtOH exposure changes long-term consumption patterns producing behavioral and neural dysfunctions that persist across the lifespan. PMID:26930631

  7. Neural control of skeletal muscle cholinesterase: a study using organ-cultured rat muscle.

    PubMed Central

    Davey, B; Younkin, L H; Younkin, S G

    1979-01-01

    1. It has been proposed that the influence of innervation on the cholinesterase activity (ChE) of skeletal muscle and on end-plate ChE in particular is mediated by trophic substance(s) moved by axonal transport and released from nerve. We have tested this hypothesis using rat extensor digitorum longus (e.d.l.) and diaphragm muscles denervated in vitro for several days and then maintained in organ culture to assay putative trophic substance(s). 2. The cholinesterase activity (ChE) of rat extensor digitorum longus (e.d.l.) muscles decreased dramatically after 5 days of denervation in vivo as previously reported. The ChE of rat e.d.l. muscles denervated in vivo for 3 days and then maintained in organ culture for 2 days was essentially identical to that of muscles denervated 5 days in vivo. 3. The ChE OF E.D.L. MUSCLES DENERVATED IN VIVO FOR 3 DAYS AND THEN MAINTAINED FOR 2 DAYS IN CULTURE MEDIUM SUPPLEMENTED WITH SCIATIC NERVE OR INNERVATED MUSCLE EXTRACT WAS SIGNIFICANTLY HIGHER THAN THAT OF MUSCLES DENERVATED IN VIVO FOR 5 DAYS OR DENERVATED IN VIVO FOR 3 DAYS AND THEN CULTURED FOR 2 DAYS IN CULTURE MEDIUM ALONE. Supplementing the culture medium with brain or spinal cord extract also significantly increased the ChE of organ-cultured e.d.l. muscles. 4. Supplementing the culture medium with liver or spleen extract or with the extract of muscle denervated for 3--7 days in vivo before extraction did not increase the ChE or organ-cultured e.d.l. muscles. 5. The effect of muscle extract on the ChE of organ-cultured e.d.l. muscles was dose dependent and occurred gradually reaching a maximum after approximately 24 h of culture. 6. Substance(s) which increased the ChE of organ-cultured e.d.l. muscles were found to accumulate in transected sciatic nerve in the region just proximal to the site of transection where substances moved by axonal transport are known to accumulate. 7. Media conditioned with neurally stimulated e.d.l. or diaphragm muscles caused a substantial and

  8. Adaptations of young adult rat cortical bone to 14 days of spaceflight

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

    1992-01-01

    To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

  9. 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

  10. 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

  11. Perinatal exposure to diethylstilbestrol alters the functional differentiation of the adult rat uterus.

    PubMed

    Bosquiazzo, Verónica L; Vigezzi, Lucía; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2013-11-01

    The exposure to endocrine disrupters and female reproductive tract disorders has not been totally clarified. The present study assessed the long-term effect of perinatal (gestation+lactation) exposure to diethylstilbestrol (DES) on the rat uterus and the effect of estrogen replacement therapy. DES (5μg/kg bw/day) was administered in the drinking water from gestational day 9 until weaning and we studied the uterus of young adult (PND90) and adult (PND360) females. To investigate whether perinatal exposure to DES modified the uterine response to a long-lasting estrogen treatment, 12-month-old rats exposed to DES were ovariectomized and treated with 17β-estradiol for 3 months (PND460). In young adult rats (PND90), the DES treatment decreased both the proliferation of glandular epithelial cells and the percentage of glandular perimeter occupied by α-smooth muscle actin-positive cells. The other tissue compartments remained unchanged. Cell apoptosis was not altered in DES-exposed females. In control adult rats (PND360), there were some morphologically abnormal uterine glands. In adult rats exposed to DES, the incidence of glands with cellular anomalies increased. In response to estrogens (PND460), the incidence of cystic glands increased in the DES group. We observed glands with daughter glands and conglomerates of glands only on PND460 and in response to estrogen replacement therapy, independently of DES exposure. The p63 isoforms were expressed without changes on PND460. Estrogen receptors α and β showed no changes, while the progesterone receptor decreased in the subepithelial stroma of DES-exposed animals with estrogen treatment. The long-lasting effects of perinatal exposure to DES included the induction of abnormalities in uterine tissues of aged female rats and an altered response of the adult uterus to estradiol. PMID:23454116

  12. In Vivo Tumorigenesis Was Observed after Injection of In Vitro Expanded Neural Crest Stem Cells Isolated from Adult Bone Marrow

    PubMed Central

    Neirinckx, Virginie; Hennuy, Benoit; Swingland, James T.; Laudet, Emerence; Sommer, Lukas; Shakova, Olga; Bours, Vincent; Rogister, Bernard

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. PMID:23071568

  13. The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus

    PubMed Central

    Wainwright, Steven R.; Galea, Liisa A. M.

    2013-01-01

    Depression is a devastating and prevalent disease, with profound effects on neural structure and function; however the etiology and neuropathology of depression remain poorly understood. Though antidepressant drugs exist, they are not ideal, as only a segment of patients are effectively treated, therapeutic onset is delayed, and the exact mechanism of these drugs remains to be elucidated. Several theories of depression do exist, including modulation of monoaminergic neurotransmission, alterations in neurotrophic factors, and the upregulation of adult hippocampal neurogenesis, and are briefly mentioned in the review. However none of these theories sufficiently explains the pathology and treatment of depression unto itself. Recently, neural plasticity theories of depression have postulated that multiple aspects of brain plasticity, beyond neurogenesis, may bridge the prevailing theories. The term “neural plasticity” encompasses an array of mechanisms, from the birth, survival, migration, and integration of new neurons to neurite outgrowth, synaptogenesis, and the modulation of mature synapses. This review critically assesses the role of adult hippocampal neurogenesis and the cell adhesion molecule, PSA-NCAM (which is known to be involved in many facets of neural plasticity), in depression and antidepressant treatment. PMID:23691371

  14. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

    PubMed

    Wislet-Gendebien, Sabine; Poulet, Christophe; Neirinckx, Virginie; Hennuy, Benoit; Swingland, James T; Laudet, Emerence; Sommer, Lukas; Shakova, Olga; Bours, Vincent; Rogister, Bernard

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. PMID:23071568

  15. Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

    PubMed Central

    Wang, Tongguang; Choi, Elliot; Monaco, Maria Chiara G.; Campanac, Emilie; Medynets, Marie; Do, Thao; Rao, Prashant; Johnson, Kory R.; Elkahloun, Abdel G.; Von Geldern, Gloria; Johnson, Tory; Subramaniam, Sriram; Hoffman, Dax; Major, Eugene; Nath, Avindra

    2013-01-01

    Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. PMID:24303066

  16. Long-Term Survival of Human Neural Stem Cells in the Ischemic Rat Brain upon Transient Immunosuppression

    PubMed Central

    Rota Nodari, Laura; Ferrari, Daniela; Giani, Fabrizio; Bossi, Mario; Rodriguez-Menendez, Virginia; Tredici, Giovanni; Delia, Domenico; Vescovi, Angelo Luigi; De Filippis, Lidia

    2010-01-01

    Understanding the physiology of human neural stem cells (hNSCs) in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs) from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps) upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells) and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably, transplanted Ih

  17. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    SciTech Connect

    Park, Kyoung Ho; Yeo, Sang Won; Troy, Frederic A.

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  18. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone

    PubMed Central

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis. PMID:25852474

  19. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone.

    PubMed

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis. PMID:25852474

  20. Pan-neuronal maturation but not neuronal subtype differentiation of adult neural stem cells is mechanosensitive

    PubMed Central

    Keung, Albert J.; Dong, Meimei; Schaffer, David V.; Kumar, Sanjay

    2013-01-01

    Most past studies of the biophysical regulation of stem cell differentiation have focused on initial lineage commitment or proximal differentiation events. It would be valuable to understand whether biophysical inputs also influence distal endpoints more closely associated with physiological function, such as subtype specification in neuronal differentiation. To explore this question, we cultured adult neural stem cells (NSCs) on variable stiffness ECMs under conditions that promote neuronal fate commitment for extended time periods to allow neuronal subtype differentiation. We find that ECM stiffness does not modulate the expression of NeuroD1 and TrkA/B/C or the percentages of pan-neuronal, GABAergic, or glutamatergic neuronal subtypes. Interestingly, however, an ECM stiffness of 700 Pa maximizes expression of pan-neuronal markers. These results suggest that a wide range of stiffnesses fully permit pan-neuronal NSC differentiation, that an intermediate stiffness optimizes expression of pan-neuronal genes, and that stiffness does not impact commitment to particular neuronal subtypes. PMID:23660869

  1. Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation

    SciTech Connect

    Capkovic, Katie L.; Stevenson, Severin; Johnson, Marc C.; Thelen, Jay J.; Cornelison, D.D.W.

    2008-04-15

    Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression.

  2. Neural cell adhesion molecule (NCAM) marks adult myogenic cells committed to differentiation.

    PubMed

    Capkovic, Katie L; Stevenson, Severin; Johnson, Marc C; Thelen, Jay J; Cornelison, D D W

    2008-04-15

    Although recent advances in broad-scale gene expression analysis have dramatically increased our knowledge of the repertoire of mRNAs present in multiple cell types, it has become increasingly clear that examination of the expression, localization, and associations of the encoded proteins will be critical for determining their functional significance. In particular, many signaling receptors, transducers, and effectors have been proposed to act in higher-order complexes associated with physically distinct areas of the plasma membrane. Adult muscle stem cells (satellite cells) must, upon injury, respond appropriately to a wide range of extracellular stimuli: the role of such signaling scaffolds is therefore a potentially important area of inquiry. To address this question, we first isolated detergent-resistant membrane fractions from primary satellite cells, then analyzed their component proteins using liquid chromatography-tandem mass spectrometry. Transmembrane and juxtamembrane components of adhesion-mediated signaling pathways made up the largest group of identified proteins; in particular, neural cell adhesion molecule (NCAM), a multifunctional cell-surface protein that has previously been associated with muscle regeneration, was significant. Immunohistochemical analysis revealed that not only is NCAM localized to discrete areas of the plasma membrane, it is also a very early marker of commitment to terminal differentiation. Using flow cytometry, we have sorted physically homogeneous myogenic cultures into proliferating and differentiating fractions based solely upon NCAM expression. PMID:18308302

  3. The Molecular Profiles of Neural Stem Cell Niche in the Adult Subventricular Zone

    PubMed Central

    Lee, Cheol; Hu, Jingqiong; Ralls, Sherry; Kitamura, Toshio; Loh, Y. Peng; Yang, Yanqin; Mukouyama, Yoh-suke; Ahn, Sohyun

    2012-01-01

    Neural stem cells (NSCs) reside in a unique microenvironment called the neurogenic niche and generate functional new neurons. The neurogenic niche contains several distinct types of cells and interacts with the NSCs in the subventricular zone (SVZ) of the lateral ventricle. While several molecules produced by the niche cells have been identified to regulate adult neurogenesis, a systematic profiling of autocrine/paracrine signaling molecules in the neurogenic regions involved in maintenance, self-renewal, proliferation, and differentiation of NSCs has not been done. We took advantage of the genetic inducible fate mapping system (GIFM) and transgenic mice to isolate the SVZ niche cells including NSCs, transit-amplifying progenitors (TAPs), astrocytes, ependymal cells, and vascular endothelial cells. From the isolated cells and microdissected choroid plexus, we obtained the secretory molecule expression profiling (SMEP) of each cell type using the Signal Sequence Trap method. We identified a total of 151 genes encoding secretory or membrane proteins. In addition, we obtained the potential SMEP of NSCs using cDNA microarray technology. Through the combination of multiple screening approaches, we identified a number of candidate genes with a potential relevance for regulating the NSC behaviors, which provide new insight into the nature of neurogenic niche signals. PMID:23209762

  4. Neural and behavioral responses to attractiveness in adult and infant faces.

    PubMed

    Hahn, Amanda C; Perrett, David I

    2014-10-01

    Facial attractiveness provides a very powerful motivation for sexual and parental behavior. We therefore review the importance of faces to the study of neurobiological control of human reproductive motivations. For heterosexual individuals there is a common brain circuit involving the nucleus accumbens, the medial prefrontal, dorsal anterior cingulate and the orbitofrontal cortices that is activated more by attractive than unattractive faces, particularly for faces of the opposite sex. Behavioral studies indicate parallel effects of attractiveness on incentive salience or willingness to work to see faces. There is some evidence that the reward value of opposite sex attractiveness is more pronounced in men than women, perhaps reflecting the greater importance assigned to physical attractiveness by men when evaluating a potential mate. Sex differences and similarities in response to facial attractiveness are reviewed. Studies comparing heterosexual and homosexual observers indicate the orbitofrontal cortex and mediodorsal thalamus are more activated by faces of the desired sex than faces of the less-preferred sex, independent of observer gender or sexual orientation. Infant faces activate brain regions that partially overlap with those responsive to adult faces. Infant faces provide a powerful stimulus, which also elicits sex differences in behavior and brain responses that appear dependent on sex hormones. There are many facial dimensions affecting perceptions of attractiveness that remain unexplored in neuroimaging, and we conclude by suggesting that future studies combining parametric manipulation of face images, brain imaging, hormone assays and genetic polymorphisms in receptor sensitivity are needed to understand the neural and hormonal mechanisms underlying reproductive drives. PMID:25199981

  5. Effect of different doses of Malaysian honey on reproductive parameters in adult male rats.

    PubMed

    Mohamed, M; Sulaiman, S A; Jaafar, H; Sirajudeen, K N S

    2012-05-01

    The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats. PMID:21592175

  6. Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats

    PubMed Central

    AHN, JI HYEON; CHEN, BAI HUI; SHIN, BICH-NA; LEE, TAE-KYEONG; CHO, JEONG HWI; KIM, IN HYE; PARK, JOON HA; LEE, JAE-CHUL; TAE, HYUN-JIN; LEE, CHOONG-HYUN; WON, MOO-HO; LEE, YUN LYUL; CHOI, SOO YOUNG; HONG, SEONGKWEON

    2016-01-01

    Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN-immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging. PMID:27221506

  7. Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats.

    PubMed

    Ahn, Ji Hyeon; Chen, Bai Hui; Shin, Bich-Na; Lee, Tae-Kyeong; Cho, Jeong Hwi; Kim, In Hye; Park, Joon Ha; Lee, Jae-Chul; Tae, Hyun-Jin; Lee, Choong-Hyun; Won, Moo-Ho; Lee, Yun Lyul; Choi, Soo Young; Hong, Seongkweon

    2016-07-01

    Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN‑immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging. PMID:27221506

  8. Testis structure and function in a nongenetic hyperadipose rat model at prepubertal and adult ages.

    PubMed

    França, L R; Suescun, M O; Miranda, J R; Giovambattista, A; Perello, M; Spinedi, E; Calandra, R S

    2006-03-01

    There are few data for hormonal levels and testis structure and function during postnatal development in rats neonatally treated with monosodium L-glutamate (MSG). In our study, newborn male pups were ip injected with MSG (4 mg/g body weight) every 2 d up to 10 d of age and investigated at prepubertal and adult ages. Plasma levels of leptin, LH, FSH, prolactin, testosterone (T), corticosterone, and free T4 (FT4) were measured. MSG rats displayed elevated circulating levels of corticosterone and hyperadiposity/hyperleptinemia, regardless of the age examined; conversely, circulating prolactin levels were not affected. Moreover, prepubertal MSG rats revealed a significant (P < 0.05) reduction in testis weight and the number of Sertoli (SC) and Leydig cells per testis. Leptin plasma levels were severalfold higher (2.41 vs. 8.07; P < 0.05) in prepubertal MSG rats, and these animals displayed plasma LH, FSH, T, and FT4 levels significantly decreased (P < 0.05). Taken together, these data indicate that testis development, as well as SC and Leydig cell proliferation, were disturbed in prepubertal MSG rats. Adult MSG rats also displayed significantly higher leptin plasma levels (7.26 vs. 27.04; P < 0.05) and lower (P < 0.05) LH and FSH plasma levels. However, T and FT4 plasma levels were normal, and no apparent alterations were observed in testis structure of MSG rats. Only the number of SCs per testis was significantly (P < 0.05) reduced in the adult MSG rats. In conclusion, although early installed hyperadipose/hyperleptinemia phenotype was probably responsible for the reproductive axis damages in MSG animals, it remains to be investigated whether this condition is the main factor for hypothalamus-pituitary-gonadal axis dysfunction in MSG rats. PMID:16339210

  9. Modeling binge-like ethanol drinking by peri-adolescent and adult P rats

    PubMed Central

    Bell, Richard L.; Rodd, Zachary A.; Smith, Rebecca J.; Toalston, Jamie E.; Franklin, Kelle M.; McBride, William J.

    2011-01-01

    Alcohol binge-drinking, especially among adolescents and young adults, is a serious public health concern. The present study examined ethanol binge-like drinking by peri-adolescent [postnatal days (PNDs 30—72)] and adult (PNDs 90—132) alcohol-preferring (P) rats with a drinking-in-the-dark—multiple-scheduled-acces (DID-MSA) procedure used by our laboratory. Male and female P rats were provided concurrent access to 15% and 30% ethanol for three 1-hr sessions across the dark cycle 5 days/week. For the 1st week, adolescent and adult female P rats consumed 3.4 and 1.6 g/kg of ethanol, respectively, during the 1st hr of access, whereas for male rats the values were 3.5 and 1.1 g/kg of ethanol, respectively. Adult intakes increased to ~2.0 g/kg/hr and adolescent intakes decreased to ~2.5 g/kg/hr across the 6 weeks of ethanol access. The daily ethanol intake of adult DID-MSA rats approximated or modestly exceeded that seen in continuous access (CA) rats or the selection criterion for P rats (≥ 5g/kg/day). However, in general, the daily ethanol intake of DID-MSA peri-adolescent rats significantly exceeded that of their CA counterparts. BELs were assessed at 15-min intervals across the 3rd hr of access during the 4th week. Ethanol intake was 1.7 g/kg vs. 2.7 g/kg and BELs were 57 mg% vs. 100 mg% at 15- and 60-min, respectively. Intoxication induced by DID-MSA in female P rats was assessed during the 1st vs. 4th week of ethanol access. Level of impairment did not differ between the 2 weeks (106 vs. 97 sec latency to fall, 120 sec criterion) and was significant (vs. naïve controls) only during the 4th week. Overall, these findings support the use of the DID-MSA procedure in rats, and underscore the presence of age- and sex-dependent effects mediating ethanol binge-like drinking in P rats. PMID:21824488

  10. Assessing the user experience of older adults using a neural network trained to recognize emotions from brain signals.

    PubMed

    Meza-Kubo, Victoria; Morán, Alberto L; Carrillo, Ivan; Galindo, Gilberto; García-Canseco, Eloisa

    2016-08-01

    The use of Ambient Assisted Living (AAL) technologies as a means to cope with problems that arise due to an increasing and aging population is becoming usual. AAL technologies are used to prevent, cure and improve the wellness and health conditions of the elderly. However, their adoption and use by older adults is still a major challenge. User Experience (UX) evaluations aim at aiding on this task, by identifying the experience that a user has while interacting with an AAL technology under particular conditions. This may help designing better products and improve user engagement and adoption of AAL solutions. However, evaluating the UX of AAL technologies is a difficult task, due to the inherent limitations of their subjects and of the evaluation methods. In this study, we validated the feasibility of assessing the UX of older adults while they use a cognitive stimulation application using a neural network trained to recognize pleasant and unpleasant emotions from electroencephalography (EEG) signals by contrasting our results with those of additional self-report and qualitative analysis UX evaluations. Our study results provide evidence about the feasibility of assessing the UX of older adults using a neural network that take as input the EEG signals; the classification accuracy of our neural network ranges from 60.87% to 82.61%. As future work we will conduct additional UX evaluation studies using the three different methods, in order to appropriately validate these results. PMID:27392644

  11. Cellular transfer of experimental allergic encephalomyelitis employing suckling and adult Lewis rats.

    PubMed

    Fujinami, R S; Paterson, P Y

    1981-07-01

    Experiments designed to assess the importance of age of donors and recipients in cellular transfer of experimental allergic encephalomyelitis (EAE) in inbred Lewis rats indicate: (a) that lymph node cells (LNC) of suckling rats sensitized to neuroantigen-adjuvant are just as effective in transfer of the disease to adult recipients as LNC from similarly sensitized adult donors, (b) that EAE can be transferred to suckling rats just as well as adults using lymphoid cells from either suckling or adult donors, and (c) while relatively low numbers of sensitized splenocytes from suckling or adult donors may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis rats. PMID:6973635

  12. Low dose 4-MBC effect on neuroendocrine regulation of reproductive axis in adult male rats.

    PubMed

    Carou, Maria E; Ponzo, Osvaldo J; Cardozo Gutierrez, Romina P; Szwarcfarb, Berta; Deguiz, Maria L; Reynoso, Roxana; Carbone, Silvia; Moguilevsky, Jaime A; Scacchi, Pablo

    2008-09-01

    4-Methylbenzylidene camphor (4-MBC) is an ultraviolet absorbent. The objective of this paper was to evaluate the effect of 4-MBC low-dose exposure on the neuroendocrine reproductive regulation in male rats. Wistar male adult rats were injected sc. with 4-MBC during 5 days with a dose of 2 and 10mg/kg or during 2 days with a dose of 2 and 20mg/kg. In all rats serum prolactin, LH and FSH concentration were assayed. The hypothalamus of rats injected during 2 days were also dissected to study GnRH release. Rats that received 2 and 10mg/kg of 4-MBC during 5 days showed a decrease in the LH and FSH serum concentration. In rats injected during 2 days, serum LH decreased with 2 and 20mg/kg and FSH decreased with 2mg/kg of 4-MBC. In vitro hypothalamic GnRH release also decreased in these animals. These results show that low doses of 4-MBC inhibit the reproductive axis in adult male rats. PMID:21783915

  13. The Effects of Inflammatory Tooth Pain on Anxiety in Adult Male Rats

    PubMed Central

    Raoof, Maryam; Ebrahimnejad, Hamed; Abbasnejad, Mehdi; Amirkhosravi, Ladan; Raoof, Ramin; Esmaeili Mahani, Saeed; Ramazani, Mohsen; Shokouhinejad, Noushin; Khoshkhounejad, Mehrfam

    2016-01-01

    Introduction: This study aimed to examine the effects of induced inflammatory tooth pain on anxiety level in adult male rats. Methods: The mandibular incisors of 56 adult male rats were cut off and prefabricated crowns were fixed on the teeth. Formalin and capsaicin were injected intradentally to induce inflammatory tooth pain. Diazepam treated group received diazepam 30 minutes before intradental injection. The anxiety-related behavior was evaluated with elevated plus maze test. Results: Intradental application of chemical noxious stimuli, capsaicin and formalin, significantly affected nociceptive behaviors (P<0.001). Capsaicin (P<0.001) and formalin (P<0.01) significantly increased the anxiety levels in rats by decrease in the duration of time spent in open arm and increase in the duration of time spent in closed arm. Rats that received capsaicin made fewer open arm entries compared to the control animals (P<0.05). Capsaicin (P<0.001) and formalin (P<0.01) treated rats showed more stretch attend postures compared to the control and sham operated animals. In diazepampretreated rats, capsaicin induced algesic effect was prevented (P<0.001). Conclusion: Inflammatory pulpal pain has anxiogenic effect on rats, whereas diazepam premedication showed both anxiolytic and pain reducing effects. PMID:27563419

  14. PSA-NCAM(+) neural precursor cells from human embryonic stem cells promote neural tissue integrity and behavioral performance in a rat stroke model.

    PubMed

    Kim, Han-Soo; Choi, Seong-Mi; Yang, Wonsuk; Kim, Dae-Sung; Lee, Dongjin R; Cho, Sung-Rae; Kim, Dong-Wook

    2014-12-01

    Recently, cell-based therapy has been highlighted as an alternative to treating ischemic brain damage in stroke patients. The present study addresses the therapeutic potential of polysialic acid-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (NPC(PSA-NCAM+)) derived from human embryonic stem cells (hESCs) in a rat stroke model with permanent middle cerebral artery occlusion. Data showed that rats transplanted with NPC(PSA-NCAM+) are superior to those treated with phosphate buffered saline (PBS) or mesenchymal stem cells (MSCs) in behavioral performance throughout time points. In order to investigate its underlying events, immunohistochemical analysis was performed on rat ischemic brains treated with PBS, MSCs, and NPC(PSA-NCAM+). Unlike MSCs, NPC(PSA-NCAM+) demonstrated a potent immunoreactivity against human specific nuclei, doublecortin, and Tuj1 at day 26 post-transplantation, implying their survival, differentiation, and integration in the host brain. Significantly, NPC(PSA-NCAM+) evidently lowered the positivity of microglial ED-1 and astrocytic GFAP, suggesting a suppression of adverse glial activation in the host brain. In addition, NPC(PSA-NCAM+) elevated α-SMA(+) immunoreactivity and the expression of angiopoietin-1 indicating angiogenic stimulation in the host brain. Taken together, the current data demonstrate that transplanted NPC(PSA-NCAM+) preserve brain tissue with reduced infarct size and improve behavioral performance through actions encompassing anti-reactive glial activation and pro-angiogenic activity in a rat stroke model. In conclusion, the present findings support the potentiality of NPC(PSA-NCAM+) as the promising source in the development of cell-based therapy for neurological diseases including ischemic stroke. PMID:24974101

  15. Effect of High Glucose on Stress-Induced Senescence of Nucleus Pulposus Cells of Adult Rats

    PubMed Central

    Kong, Jae-Gwan; Lee, Donghwan; Park, Eun-Young

    2015-01-01

    Study Design In vitro cell culture model. Purpose We investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells. Overview of Literature DM is a major public health issue worldwide, especially adult-onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM-associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells. Methods Adult NP cells were isolated from 24-week-old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence-associated-beta-galactosidase (SA-β-Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53-p21-pRB) and stress-induced premature senescence (p16-pRB) pathways. Results The mean SA-β-Gal-positive percentage was increased in adult rat NP cells treated with high glucose in a dose- and time-dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations. Conclusions The current study demonstrated that high glucose accelerated stress-induced senescence in adult rat NP cells in a dose- and time-dependent manner. Accelerated stress-induced senescence in adult NP cells could be an emerging risk factor for intervertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM. PMID:25901224

  16. Zinc deficiency induces depression-like symptoms in adult rats.

    PubMed

    Tassabehji, Nadine M; Corniola, Rikki S; Alshingiti, Almamoun; Levenson, Cathy W

    2008-10-20

    There is mounting evidence suggesting a link between serum zinc levels and clinical depression. Not only is serum zinc negatively correlated with the severity of symptoms, but zinc levels appear to be lowest in patients who do not respond to antidepressant drug therapy. It is not known if reduced zinc levels are contributing to depression, or the result of dietary or other factors associated with major depression. Thus, we designed this study to test the hypothesis that dietary zinc deficiency would induce depression-like behaviors in rats. Two-month-old male rats were fed zinc adequate (ZA, 30 ppm), deficient (ZD, 1 ppm), or supplemented (ZS, 180 ppm) diets for 3 weeks. Consistent with the development of depression, ZD rats displayed anorexia (p<0.001), anhedonia (reduced saccharin:water intake, p< 0.001), and increased anxiety-like behaviors in a light-dark box test (p<0.05). Furthermore, the antidepressant drug fluoxetine (10 mg/kg body wt) reduced behavioral despair, as measured by the forced swim test, in rats fed the ZA and ZS rats (p<0.05), but was ineffective in ZD rats. Together these studies suggest that zinc deficiency leads to the development of depression-like behaviors that may be refractory to antidepressant treatment. PMID:18655800

  17. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-09-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 {mu}g/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 {mu}g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  18. Conditioned Place Preference and Self-Administration Induced by Nicotine in Adolescent and Adult Rats

    PubMed Central

    Ahsan, Hafiz Muhammad; de la Peña, June Bryan I.; Botanas, Chrislean Jun; Kim, Hee Jin; Yu, Gu Yong; Cheong, Jae Hoon

    2014-01-01

    Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine. PMID:25414778

  19. Conditioned place preference and self-administration induced by nicotine in adolescent and adult rats.

    PubMed

    Ahsan, Hafiz Muhammad; de la Peña, June Bryan I; Botanas, Chrislean Jun; Kim, Hee Jin; Yu, Gu Yong; Cheong, Jae Hoon

    2014-09-01

    Nicotine addiction is a worldwide problem. However, previous studies characterizing the rewarding and reinforcing effects of nicotine in animal models have reported inconsistent findings. It was observed that the addictive effects are variable on different factors (e.g. route, dose, and age). Here, we evaluated the rewarding and reinforcing effects of nicotine in different routes of administration, across a wide dose range, and in different age groups. Two of the most widely used animal models of drug addiction were employed: the conditioned place preference (CPP) and self-administration (SA) tests. Nicotine CPP was evaluated in different routes [intraperitoneal (i.p.) and subcutaneous (s.c.)], doses (0.05 to 1.0 mg/kg) and age [adolescent and adult rats]. Similarly, intravenous nicotine SA was assessed in different doses (0.01 to 0.06 mg/kg/infusion) and age (adolescent and adult rats). In the CPP test, s.c. nicotine produced greater response than i.p. The 0.2 mg/kg dose produced highest CPP response in adolescent, while 0.6 mg/kg in adult rats; which were also confirmed in 7 days pretreated rats. In the SA test, adolescent rats readily self-administer 0.03 mg/kg/infusion of nicotine. Doses that produced nicotine CPP and SA induced blood nicotine levels that corresponded well with human smokers. In conclusion, we have demonstrated that nicotine produces reliable CPP [0.2 mg/kg dose (s.c.)] in adolescents and [0.6 mg/kg dose (s.c.)] in adults, and SA [0.03 mg/kg/infusion] in adolescent rats. Both tests indicate that adolescent rats are more sensitive to the rewarding and reinforcing effects of nicotine. PMID:25414778

  20. Postnatal masculinization alters the HPA axis phenotype in the adult female rat

    PubMed Central

    Seale, JV; Wood, SA; Atkinson, HC; Harbuz, MS; Lightman, SL

    2005-01-01

    The ability of postnatal testosterone propionate (TP) to masculinize both behaviour and gonadal cyclicity in the female rat is well documented. We have investigated whether postnatal androgen also has an organizational effect on another sexually dimorphic neuroendocrine system – the hypothalamo-pituitary-adrenal (HPA) axis. Female rats were exposed to a single injection of testosterone propionate (TP) or oil within 24 h of birth. As adults, rats were either ovariectomized and given 17β-oestradiol replacement (OVXE2) or sham ovariectomized with cholesterol implants (SHOVX). An automated sampling system collected blood from unanaesthetized adult female rats every 10 min over a 24-h period, during a mild psychological stress (noise) and following an immunological lipopolysaccharide stress (LPS). Neonatal TP-treated SHOVX rats had a significant reduction in the number, height, frequency and amplitude of corticosterone pulses over the basal 24-h period, compared to both the neonatal oil-treated and TP-treated OVXE2 animals. The corticosterone response to both noise and LPS was also significantly decreased for the TP-treated SHOVX females. Three hours post-LPS administration, TP females had significantly lower values of paraventricular nucleus (PVN) corticotrophin releasing hormone (CRH), arginine vasopressin (AVP) and anterior pituitary proopiomelanocortin (POMC) mRNAs and greater PVN glucocorticoid receptor (GR) mRNA expression compared to the oil-treated controls. E2 replacement in adult TP rats normalized all the mRNA levels, except for PVN GR mRNA which did fall towards the levels of the oil-control animals. A single injection of TP within 24 h of birth disrupts the development of the characteristic female pattern of corticosterone secretion and the normal female HPA response to stress, resulting in a pattern similar to that seen in males. These effects can be reversed by E2 treatment in the adult TP female rat. PMID:15611026

  1. Time Course of Elevated Ethanol Intake in Adolescent Relative to Adult Rats Under Continuous, Voluntary-Access Conditions

    PubMed Central

    Vetter, Courtney S.; Doremus-Fitzwater, Tamara L.; Spear, Linda P.

    2007-01-01

    Background Adolescence is a period of elevated alcohol consumption in humans as well as in animal models. Previous studies in our laboratory have shown that adolescent Sprague–Dawley rats consume approximately 2 times more ethanol on a gram per kilogram basis than adult animals in a 2-bottle choice free-access situation. The purpose of the present study was to examine the time course and pattern of elevated ethanol intake during adolescence and the adolescent-to-adult transition, contrast this intake with ontogenetic patterns of food and water intake, and determine whether adolescent access to ethanol elevates voluntary consumption of ethanol in adulthood. Methods Adolescent [postnatal day (P)27–28] and adult (P69–70) male Sprague–Dawley rats were singly housed with continuous access to both water and 1 of 3 experimental solutions in ball-bearing–containing sipper tubes: unsweetened ethanol (10% v/v), sweetened ethanol (10% v/v+0.1% w/v saccharin), and saccharin alone (0.1% w/v). Results Ethanol consumption plateaued at approximately 7.5 g/kg/d during the first 2 weeks of measurement (i.e., P28–39) in early adolescence, before declining sharply at approximately P40 to levels that were only modestly elevated compared with adult-typical consumption patterns that were reached by approximately P70. In contrast, intake of food and total calories showed a more gradual decline into adulthood with no distinguishable plateaus in early adolescence. When adolescent-initiated and adult-initiated animals were tested at the same chronological age in adulthood, animals drank similar amounts regardless of the age at which they were first given voluntary access to ethanol. Conclusions Taken together, these data suggest that the elevated ethanol intake characteristic of early-to-mid adolescence is not simply a function of adolescent-typical hyperphagia or hyperdipsia, but instead may reflect age-related differences in neural substrates contributing to the rewarding or

  2. Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats

    PubMed Central

    Carroll, Marilyn E.

    2010-01-01

    Rationale In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress. Objective The purpose of this study was to compare adolescent and adult rats on drug-, cue-, and stress-induced reinstatement of cocaine-seeking behavior. Methods On postnatal days 23 (adolescents) and 90 (adults), rats were implanted with intravenous catheters and trained to lever press for i.v. infusions of cocaine (0.4 mg/kg) during two daily 2-h sessions. The rats then self-administered i.v. cocaine for ten additional sessions. Subsequently, visual and auditory stimuli that signaled drug delivery were unplugged, and rats were allowed to extinguish lever pressing for 20 sessions. Rats were then tested on cocaine-, cue-, and yohimbine (stress)-induced cocaine seeking using a within-subject multicomponent reinstatement procedure. Results Results indicated that adolescents had heightened cocaine seeking during maintenance and extinction compared to adults. During reinstatement, adolescents (vs adults) responded more following cocaine- and yohimbine injections, while adults (vs adolescents) showed greater responding following presentations of drug-associated cues. Conclusion These results demonstrated that adolescents and adults differed across several measures of drug-seeking behavior, and adolescents may be especially vulnerable to relapse precipitated by drugs and stress. PMID:19953228

  3. Dietary Iron Concentration May Influence Aging Process by Altering Oxidative Stress in Tissues of Adult Rats

    PubMed Central

    Arruda, Lorena Fernandes; Arruda, Sandra Fernandes; Campos, Natália Aboudib; de Valencia, Fernando Fortes; Siqueira, Egle Machado de Almeida

    2013-01-01

    Iron is an essential element. However, in its free form, iron participates in redox-reactions, leading to the production of free radicals that increase oxidative stress and the risk of damaging processes. Living organisms have an efficient mechanism that regulates iron absorption according to their iron content to protect against oxidative damage. The effects of restricted and enriched-iron diets on oxidative stress and aging biomarkers were investigated. Adult Wistar rats were fed diets containing 10, 35 or 350 mg/kg iron (adult restricted-iron, adult control-iron and adult enriched-iron groups, respectively) for 78 days. Rats aged two months were included as a young control group. Young control group showed higher hemoglobin and hematocrit values, lower levels of iron and lower levels of MDA or carbonyl in the major studied tissues than the adult control group. Restricted-iron diet reduced iron concentrations in skeletal muscle and oxidative damage in the majority of tissues and also increased weight loss. Enriched-iron diet increased hematocrit values, serum iron, gamma-glutamyl transferase, iron concentrations and oxidative stress in the majority of tissues. As expected, young rats showed higher mRNA levels of heart and hepatic L-Ferritin (Ftl) and kidneys SMP30 as well as lower mRNA levels of hepatic Hamp and interleukin-1 beta (Il1b) and also lower levels of liver protein ferritin. Restricted-iron adult rats showed an increase in heart Ftl mRNA and the enriched-iron adult rats showed an increase in liver nuclear factor erythroid derived 2 like 2 (Nfe2l2) and Il1b mRNAs and in gut divalent metal transporter-1 mRNA (Slc11a2) relative to the control adult group. These results suggest that iron supplementation in adult rats may accelerate aging process by increasing oxidative stress while iron restriction may retards it. However, iron restriction may also impair other physiological processes that are not associated with aging. PMID:23593390

  4. Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone.

    PubMed

    Bunk, Eva C; Ertaylan, Gökhan; Ortega, Felipe; Pavlou, Maria A; Gonzalez Cano, Laura; Stergiopoulos, Athanasios; Safaiyan, Shima; Völs, Sandra; van Cann, Marianne; Politis, Panagiotis K; Simons, Mikael; Berninger, Benedikt; Del Sol, Antonio; Schwamborn, Jens C

    2016-08-01

    Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thus, our work uncovers a novel function of Prox1 as a fate determinant for oligodendrocytes in the adult mammalian brain. These data indicate that the neurogenic and oligodendrogliogenic lineages in the two adult neurogenic niches exhibit a distinct requirement for Prox1, being important for neurogenesis in the DG but being indispensable for oligodendrogliogenesis in the SVZ. Stem Cells 2016;34:2115-2129. PMID:27068685

  5. Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

    NASA Technical Reports Server (NTRS)

    1993-01-01

    During the last phase of NAG 2-386 we completed three studies. The effects of 14 days of weightlessness; the vastus medialis (VM) from flight rats in COSMOS 2044 was compared with the VM from tail suspended rats and other controls. The type I and II fibers in the mixed fiber portion of the VM were significantly reduced in flight rats and capillary densities paralleled the fiber density changes. The results of this project compared favorably with those in the extensor digitorum longus following seven days of flight in SL 3. The cardiovascular projects focused on the blood pressure changes in head down tilted rats (HDT) and non-head down tilted (N-HDT) rats. Blood pressures (MAP, SP and DP) were significantly elevated through seven days of HDT and rapidly returned to control levels within one day after removal from the HDT position. The N-HDT showed some slight rise in blood pressure but these were not as great and they were not as rapid. The HDT rats were characterized as exhibiting transient hypertension. These results led to some of the microvascular and vascular graduate student projects of Dr. Bernhard Stepke. Also our results refute or, at least, do not agree with previous reports from other laboratories. Each animal, in our blood pressure projects, served as its own control thereby providing more accurate results. Also, our experiments focused on recovery studies which can, in and of themselves, provide guidelines for flight experiments concerned with blood pressure changes. Another experiment was conducted to examine the role of testicular atrophy in whole body suspended (WBS) and tail suspended (TS) rats. We worked in conjunction with Dr. D.R. Deaver's laboratory at Pennsylvania State University and Dr. R. P. Amann at Colorado State University. In the TS rats the testes are retracted into the abdominal cavity, unless a ligature is placed to maintain them in the external scrotal sac. The cryptorchid condition in TS rats results in atrophy of the testes and

  6. Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats

    PubMed Central

    Martínez-Cerdeño, Verónica; Noctor, Stephen C.; Espinosa, Ana; Ariza, Jeanelle; Parker, Philip; Orasji, Samantha; Daadi, Marcel M.; Bankiewicz, Krystof; Alvarez-Buylla, Arturo; Kriegstein, Arnold R.

    2014-01-01

    SUMMARY We investigated a strategy to ameliorate the motor symptoms of rats that received 6-hydroxydopamine (6-OHDA) lesions, a rodent model of Parkinson’s disease, through transplantation of embryonic medial ganglionic eminence (MGE) cells into the striatum. During brain development, embryonic MGE cells migrate into the striatum and neocortex where they mature into GABAergic interneurons and play a key role in establishing the balance between excitation and inhibition. Unlike most other embryonic neurons, MGE cells retain the capacity for migration and integration when transplanted into the postnatal and adult brain. We performed MGE cell transplantation into the basal ganglia of control and 6-OHDA-lesioned rats. Transplanted MGE cells survived, differentiated into GABA+ neurons, integrated into host circuitry, and modifed motor behavior in both lesioned and control rats. Our data suggest that MGE cell transplantation into the striatum is a promising approach to investigate the potential benefits of remodeling basal ganglia circuitry in neurodegenerative diseases. PMID:20207227

  7. Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

    PubMed Central

    Kong, Lu; Tang, Meng; Zhang, Ting; Wang, Dayong; Hu, Ke; Lu, Weiqi; Wei, Chao; Liang, Geyu; Pu, Yuepu

    2014-01-01

    Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. PMID:25407529

  8. Modification of tenascin-R expression following unilateral labyrinthectomy in rats indicates its possible role in neural plasticity of the vestibular neural circuit

    PubMed Central

    Gaal, Botond; Jóhannesson, Einar Örn; Dattani, Amit; Magyar, Agnes; Wéber, Ildikó; Matesz, Clara

    2015-01-01

    We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrinthectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestibular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tenascin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors. PMID:26604908

  9. Ethanol induces second-order aversive conditioning in adolescent and adult rats

    PubMed Central

    Pautassi, Ricardo Marcos; Myers, Mallory; Spear, Linda Patia; Molina, Juan Carlos; Spear, Norman E.

    2011-01-01

    Alcohol abuse and dependence is considered a developmental disorder with etiological onset during late childhood and adolescence, and understanding age-related differences in ethanol sensitivity is important. Low to moderate ethanol doses (0.5 and 2.0 g/kg, i.g.) induce single-trial, appetitive second-order place conditioning (SOC) in adolescent, but not adult, rats. Recent studies have demonstrated that adolescents may be less sensitive than adults to the aversive properties of ethanol, reflected by conditioned taste aversion. The present study assessed the aversive motivational effects of high-dose ethanol (3.0 and 3.25 g/kg, i.g., for adolescent and adults, respectively) using SOC. These doses were derived from Experiment 1, which found similar blood and brain ethanol levels in adolescent and adult rats given 3.0 and 3.25 g/kg ethanol, respectively. In Experiment 2, animals received ethanol or vehicle paired with intraoral pulses of sucrose (conditioned stimulus 1 [CS1]). After one, two, or three conditioning trials, rats were presented with the CS1 while in a distinctive chamber (CS2). When tested for CS2 preference, ethanol-treated animals exhibited reduced preference for the CS2 compared with controls. This result, indicative of ethanol-mediated aversive place conditioning, was similar for adolescents and adults, for females and males, and after one, two, or three training trials. One finding, however, suggested that adolescents were less sensitive than adults to ethanol’s aversive effects at the intermediate level of training. In conjunction with previous results, the present study showed that in adolescent rats subjected to SOC, ethanol’s hedonic effects vary from appetitive to aversive as the ethanol dose increases. Adolescent and adult animals appear to perceive the post-ingestive effects of high-dose ethanol as similarly aversive when assessed by SOC. PMID:21187242

  10. Comparative toxicity of caffeine and aminophylline (theophylline ethylenediamine) in young and adult rats.

    PubMed

    Warszawski, D; Gorodischer, R; Kaplanski, J

    1978-01-01

    The toxicity of aminophylline and caffeine was studied in adult and 2-day-old rats following a single subcutaneous injection of the respective drug. Following the injection of high doses of either methylxanthine, adult rats developed convulsions, tremors, lethargy and licking of lips. In adult rats, the LD50 of caffeine and aminophylline was the same after 24 h and after 1 week of observation: caffeine 265 mg/kg, and aminophylline 202 mg/kg (theophylline base 172 mg/kg). In young rats, the LD50 was greater when the observation was carried out for 1 week than at 24 h after the injection; at 24 h: caffeine 220 mg/kg, and aminophylline 169 mg/kg (theophylline base 144 mg/kg); at 1 week: caffeine 155 mg/kg, and aminophylline 140 mg/kg (theophylline base 119 mg/kg). Young rats failed to gain weight at a normal rate after administration of either methylxanthine. The greater toxicity of both methylxanthines in newborn animals may be at least partly due to the extremely slow elimination of theophylline and caffeine in the neonate. PMID:698326

  11. Muscle mechanical properties of adult and older rats submitted to exercise after immobilization

    PubMed Central

    Kodama, Fábio Yoshikazu; Camargo, Regina Celi Trindade; Job, Aldo Eloizo; Ozaki, Guilherme Akio Tamura; Koike, Tatiana Emy; Camargo Filho, José Carlos Silva

    2012-01-01

    Objectives To describe the effects of immobilization, free remobilization and remobilization by physical exercise about mechanical properties of skeletal muscle of rats of two age groups. Methods 56 Wistar rats divided into two groups according to age, an adult group (five months) and an older group (15 months). These groups were subdivided in: control, immobilized, free remobilized and remobilized by physical exercise. The pelvic limb of rats was immobilized for seven days. The exercise protocol consisted of five swimming sessions, once per day and 25 minutes per session. The gastrocnemius muscle was subjected to tensile tests, and evaluated the properties: load at the maximum limit, stretching at the maximum limit and stiffness. Results The immobilization reduced the values of load at the maximum limit and the remobilization protocols were not sufficient to restore control levels in adult group and older rats. The stretching at the maximum limit differs only in the older group. Conclusions The immobilization reduces the muscle's ability to bear loads and exercise protocol tends to restore the default at control values in adult and older rats. The age factor only interfered in the stretching at the maximum limit, inducing a reduction of this property in the post-immobilization. Level of Evidence II, Investigating the Results of Treatment. PMID:24453606

  12. Embryonic Nkx2.1-expressing neural precursor cells contribute to the regional heterogeneity of adult V-SVZ neural stem cells.

    PubMed

    Delgado, Ryan N; Lim, Daniel A

    2015-11-15

    The adult ventricular-subventricular zone (V-SVZ) of the lateral ventricle produces several subtypes of olfactory bulb (OB) interneurons throughout life. Neural stem cells (NSCs) within this zone are heterogeneous, with NSCs located in different regions of the lateral ventricle wall generating distinct OB interneuron subtypes. The regional expression of specific transcription factors appears to correspond to such geographical differences in the developmental potential of V-SVZ NSCs. However, the transcriptional definition and developmental origin of V-SVZ NSC regional identity are not well understood. In this study, we found that a population of NSCs in the ventral region of the V-SVZ expresses the transcription factor Nkx2.1 and is derived from Nkx2.1-expressing (Nkx2.1+) embryonic precursors. To follow the fate of Nkx2.1+ cells and their progeny in vivo, we used mice with an Nkx2.1-CreER "knock-in" allele. Nkx2.1+ V-SVZ NSCs labeled in adult mice generated interneurons for the deep granule cell layer of the OB. Embryonic brain Nkx2.1+ precursors labeled at embryonic day 12.5 gave rise to Nkx2.1+ NSCs of the ventral V-SVZ in postnatal and adult mice. Thus, embryonic Nkx2.1+ neural precursors give rise to a population of Nkx2.1+ NSCs in the ventral V-SVZ where they contribute to the regional heterogeneity of V-SVZ NSCs. PMID:26387477

  13. The Reference Ability Neural Network Study: Life-time stability of reference-ability neural networks derived from task maps of young adults.

    PubMed

    Habeck, C; Gazes, Y; Razlighi, Q; Steffener, J; Brickman, A; Barulli, D; Salthouse, T; Stern, Y

    2016-01-15

    Analyses of large test batteries administered to individuals ranging from young to old have consistently yielded a set of latent variables representing reference abilities (RAs) that capture the majority of the variance in age-related cognitive change: Episodic Memory, Fluid Reasoning, Perceptual Processing Speed, and Vocabulary. In a previous paper (Stern et al., 2014), we introduced the Reference Ability Neural Network Study, which administers 12 cognitive neuroimaging tasks (3 for each RA) to healthy adults age 20-80 in order to derive unique neural networks underlying these 4 RAs and investigate how these networks may be affected by aging. We used a multivariate approach, linear indicator regression, to derive a unique covariance pattern or Reference Ability Neural Network (RANN) for each of the 4 RAs. The RANNs were derived from the neural task data of 64 younger adults of age 30 and below. We then prospectively applied the RANNs to fMRI data from the remaining sample of 227 adults of age 31 and above in order to classify each subject-task map into one of the 4 possible reference domains. Overall classification accuracy across subjects in the sample age 31 and above was 0.80±0.18. Classification accuracy by RA domain was also good, but variable; memory: 0.72±0.32; reasoning: 0.75±0.35; speed: 0.79±0.31; vocabulary: 0.94±0.16. Classification accuracy was not associated with cross-sectional age, suggesting that these networks, and their specificity to the respective reference domain, might remain intact throughout the age range. Higher mean brain volume was correlated with increased overall classification accuracy; better overall performance on the tasks in the scanner was also associated with classification accuracy. For the RANN network scores, we observed for each RANN that a higher score was associated with a higher corresponding classification accuracy for that reference ability. Despite the absence of behavioral performance information in the

  14. MAINTENANCE OF TESTOSTERONE PRODUCTION BY PURIFIED ADULT RAT LEYDIG CELLS FOR THREE DAYS IN VITRO

    EPA Science Inventory

    Using a preparation of highly purified, adult rat Leydig cells and conditions of culture which we found to optimize testosterone production during 24 h, we sought to maintain optimal testosterone production for 3 d. eydig cells cultured on Cytodex 3 beads at 19% O2 in Dulbecco's ...

  15. EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS

    EPA Science Inventory

    EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS. M.N. Logan1, J.R. Thibodeaux2, R.G. Hanson2, C. Lau2. 1North Carolina Central University, Durham, NC, 2Reprod. Tox. Div. NHEERL, US EPA, Research Triangle Park, NC.

    Perfluor...

  16. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats

    EPA Science Inventory

    Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoli...

  17. Prenatal Choline Availability Alters the Context Sensitivity of Pavlovian Conditioning in Adult Rats

    ERIC Educational Resources Information Center

    Lamoureux, Jeffrey A.; Meck, Warren H.; Williams, Christina L.

    2008-01-01

    The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline…

  18. REPRODUCTIVE EFFECTS OF LOW ACUTE DOSES OF CADMIUM CHLORIDE IN ADULT MALE RATS

    EPA Science Inventory

    Adult male Sprague-Dawley rats were injected sc with cadmium (Cd, as cadmium chloride) in doses ranging from 1.6 to 152 micromol Cd/kg body weight (body wt). Fourteen days after dosing, animals were evaluated for reproductive damage. Evaluations for each animal included tests, se...

  19. 5,7-DIHYDROXYTRYPTAMINE INJECTIONS INCREASE GLIAL FIBRILLARY ACIDIC PROTEIN IN THE HYPOTHALAMUS OF ADULT RATS

    EPA Science Inventory

    The distribution and level of glial fibrillary acidic protein (GFAP) were determined in the adult rat hypothalamus following axotomy of serotonin (5-HT) neurons. even days after unilateral intrahypothalamic injection of the 5-HT neurotoxic, 5,7- dihydroxytryptamine, there gas a m...

  20. IN VITRO ALUMINUM INHIBITION OF BRAIN PHOSPHOINOSITIDE METABOLISM:COMPARISON OF NEONATAL AND ADULTS RATS

    EPA Science Inventory

    Recent evidence indicates that the neurotoxic metal aluminum interferes with the phosphoinositide second messenger system in adult rats both in vitro and in vivo. e have examined the age-related effects of aluminum chloride (AlCl3) on receptor-stimulated inositol phosphate (IP) a...

  1. PREPUBERTAL EXPOSURES TO COMPOUNDS THAT INCREASE PROLACTIN SECRETION IN THE MALE RAT: EFFECTS ON ADULT PROSTATE

    EPA Science Inventory

    Prepubertal exposure to compounds that increase prolactin secretion in the male rat: effects on the adult prostate.

    Stoker TE, Robinette CL, Britt BH, Laws SC, Cooper RL.

    Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effec...

  2. Culture and proliferation of highly purified adult Schwann cells from rat, dog, and man.

    PubMed

    Haastert-Talini, Kirsten

    2012-01-01

    This chapter presents fast and easy protocols to obtain highly purified cultures of proliferating adult rat, canine, and human Schwann cells. Cell preparation from predegenerated adult sciatic nerves combined with the use of melanocyte growth medium supplemented with forskolin, fibroblast growth factor-2, pituitary extract, and heregulin as selective, serum-free culture medium and two methods for a consecutive cell-enrichment step are described. Our protocols result in approximately 90% pure Schwann cell cultures (or higher). The average time to obtain highly purified in vitro cultures of adult Schwann cells is 21 days. PMID:22367812

  3. Trading new neurons for status: Adult hippocampal neurogenesis in eusocial Damaraland mole-rats.

    PubMed

    Oosthuizen, M K; Amrein, I

    2016-06-01

    Diversity in social structures, from solitary to eusocial, is a prominent feature of subterranean African mole-rat species. Damaraland mole-rats are eusocial, they live in colonies that are characterized by a reproductive division of labor and a subdivision into castes based on physiology and behavior. Damaraland mole-rats are exceptionally long lived and reproductive animals show delayed aging compared to non-reproductive animals. In the present study, we described the hippocampal architecture and the rate of hippocampal neurogenesis of wild-derived, adult Damaraland mole-rats in relation to sex, relative age and social status or caste. Overall, Damaraland mole-rats were found to have a small hippocampus and low rates of neurogenesis. We found no correlation between neurogenesis and sex or relative age. Social status or caste was the most prominent modulator of neurogenesis. An inverse relationship between neurogenesis and social status was apparent, with queens displaying the lowest neurogenesis while the worker mole-rats had the most. As there is no natural progression from one caste to another, social status within a colony was relatively stable and is reflected in the level of neurogenesis. Our results correspond to those found in the naked mole-rat, and may reflect an evolutionary and environmentally conserved trait within social mole-rat species. PMID:26979050

  4. Preparing neural stem/progenitor cells in PuraMatrix hydrogel for transplantation after brain injury in rats: A comparative methodological study.

    PubMed

    Aligholi, Hadi; Rezayat, Seyed Mahdi; Azari, Hassan; Ejtemaei Mehr, Shahram; Akbari, Mohammad; Modarres Mousavi, Seyed Mostafa; Attari, Fatemeh; Alipour, Fatemeh; Hassanzadeh, Gholamreza; Gorji, Ali

    2016-07-01

    Cultivation of neural stem/progenitor cells (NS/PCs) in PuraMatrix (PM) hydrogel is an option for stem cell transplantation. The efficacy of a novel method for placing adult rat NS/PCs in PM (injection method) was compared to encapsulation and surface plating approaches. In addition, the efficacy of injection method for transplantation of autologous NS/PCs was studied in a rat model of brain injury. NS/PCs were obtained from the subventricular zone (SVZ) and cultivated without (control) or with scaffold (three-dimensional cultures; 3D). The effect of different approaches on survival, proliferation, and differentiation of NS/PCs were investigated. In in vivo study, brain injury was induced 45 days after NS/PCs were harvested from the SVZ and phosphate buffered saline, PM, NS/PCs, or PM+NS/PCs were injected into the brain lesion. There was an increase in cell viability and proliferation after injection and surface plating of NS/PCs compared to encapsulation and neural differentiation markers were expressed seven days after culturing the cells. Using injection method, transplantation of NS/PCs cultured in PM resulted in significant reduction of lesion volume, improvement of neurological deficits, and enhancement of surviving cells. In addition, the transplanted cells could differentiate in to neurons, astrocytes, or oligodendrocytes. Our results indicate that the injection and surface plating methods enhanced cell survival and proliferation of NS/PCs and suggest the injection method as a promising approach for transplantation of NS/PCs in brain injury. PMID:27038753

  5. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    PubMed

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion. PMID:27512001

  6. Reproducible expansion and characterization of mouse neural stem/progenitor cells in adherent cultures derived from the adult subventricular zone

    PubMed Central

    Theus, Michelle H.; Ricard, Jerome; Liebl, Daniel J.

    2012-01-01

    Endogenous neural stem/progenitor cells (NSPCs) residing in the subventricular zone (SVZ) of the adult mouse forebrain have been shown to enhance their neurogenic potential in response to CNS injury. Mechanisms involved in regulating adult neurogenesis under naïve or stressed conditions can be studied using a monolayer cell-culture system of the nestin-expressing NSPC lineage to analyze proliferation, survival and differentiation. Here, we describe a protocol for the expansion of NSPCs for studies aimed at understanding the functional role of NSPCs in maintaining adult neurogenic processes. In this unit, we outline in detail the procedures for: (1) isolation, maintenance and culture of the NSPC component of the SVZ niche from the lateral wall of the lateral ventricle; (2) characterization of NSPC functions by examining proliferation, survival and differentiation; and (3) efficient siRNA transfection methods in 96-well format. PMID:22415840

  7. Relative role of neural substrates in the aggressive behavior of rats.

    PubMed

    Patil, Shrirang N; Brid, Shivaji V

    2010-01-01

    Early animal studies have shown an association between aggression and brain dysfunction. The goal of the present study was to compare the effects of lesions of different parts of brain on aggression in rats. Adult rats (n = 40, weighing 200-260 g) were randomly divided into four groups of ten animals each and subjected to lesions of the septum (Group I), medial preoptic area (Group II), medial accumbens (Group III), and bed nucleus of stria terminalis (Group IV), using stereotaxy apparatus. Aggression toward an unfamiliar male intruder was observed before and after the lesion. The aggression score of each animal was recorded three times before lesion and averaged for use in analysis. Analysis of variance (ANOVA) was applied for finding homogeneity of the groups. Postoperative scores were also similarly recorded and summarized as mean +/- standard deviation. Pre- and post-lesion scores were compared using the t test. The scores were significantly reduced in Group I, II, and III, but increased in Group IV. We can conclude that the septum, medial preoptic area, medial accumbens, and bed nucleus of stria terminalis, by virtue of their interconnections, influence aggressive behavior. PMID:21305851

  8. 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

  9. In vivo imaging of endogenous neural stem cells in the adult brain.

    PubMed

    Rueger, Maria Adele; Schroeter, Michael

    2015-01-26

    The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'-[(18)F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting. PMID:25621107

  10. Single-cell in vivo imaging of adult neural stem cells in the zebrafish telencephalon.

    PubMed

    Barbosa, Joana S; Di Giaimo, Rossella; Götz, Magdalena; Ninkovic, Jovica

    2016-08-01

    Adult neural stem cells (aNSCs) in zebrafish produce mature neurons throughout their entire life span in both the intact and regenerating brain. An understanding of the behavior of aNSCs in their intact niche and during regeneration in vivo should facilitate the identification of the molecular mechanisms controlling regeneration-specific cellular events. A greater understanding of the process in regeneration-competent species may enable regeneration to be achieved in regeneration-incompetent species, including humans. Here we describe a protocol for labeling and repetitive imaging of aNSCs in vivo. We label single aNSCs, allowing nonambiguous re-identification of single cells in repetitive imaging sessions using electroporation of a red-reporter plasmid in Tg(gfap:GFP)mi2001 transgenic fish expressing GFP in aNSCs. We image using two-photon microscopy through the thinned skull of anesthetized and immobilized fish. Our protocol allows imaging every 2 d for a period of up to 1 month. This methodology allowed the visualization of aNSC behavior in vivo in their natural niche, in contrast to previously available technologies, which rely on the imaging of either dissociated cells or tissue slices. We used this protocol to follow the mode of aNSC division, fate changes and cell death in both the intact and injured zebrafish telencephalon. This experimental setup can be widely used, with minimal prior experience, to assess key factors for processes that modulate aNSC behavior. A typical experiment with data analysis takes up to 1.5 months. PMID:27362338

  11. Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu.

    PubMed

    Mansouri, Shiva; Lietzau, Grazyna; Lundberg, Mathias; Nathanson, David; Nyström, Thomas; Patrone, Cesare

    2016-01-01

    Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs) has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) and the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia. PMID:27305000

  12. Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu

    PubMed Central

    Mansouri, Shiva; Lietzau, Grazyna; Lundberg, Mathias; Nathanson, David; Nyström, Thomas; Patrone, Cesare

    2016-01-01

    Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs) has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) and the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia. PMID:27305000

  13. Autonomic activation associated with ethanol self-administration in adult female P rats

    PubMed Central

    Bell, Richard L.; Rodd, Zachary A.; Toalston, Jamie E.; McKinzie, David L.; Lumeng, Lawrence; Li, Ting-Kai; McBride, William J.; Murphy, James M.

    2008-01-01

    The present study examined changes in heart rate (HR) prior to and during limited access ethanol drinking in adult female P rats. P rats were implanted with radiotelemetric transmitters to measure HR. Daily testing involved a 90-min pre-test period (water only available) and a subsequent 90-min test period [either water (W) or ethanol available]. After a week of habituation, one ethanol group had access to ethanol for 7 weeks (CE), and another ethanol group had access for 4 weeks, was deprived for 2 weeks and then had access for a final week (DEP). Analyses of HR revealed that CE and DEP rats had significantly higher HR than W rats during test periods that ethanol was present and that DEP rats displayed higher HR during the early test period of the ethanol deprivation interval, as well. These data indicate that ethanol drinking induces HR activation in adult female P rats, and that this activation can be conditioned to the test cage environment, paralleling reports on contextual conditioning and cue-reactivity in alcoholics exposed to alcohol-associated stimuli. Therefore, this behavioral test may prove advantageous in screening pharmacotherapies for reducing craving and relapse, which are associated with cue-reactivity in abstinent alcoholics. PMID:18713644

  14. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation

    PubMed Central

    Barazzuol, Lara; Jeggo, Penny A.

    2016-01-01

    The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5–14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4Y288C), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4Y288C embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4Y288C mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. PMID:27125639

  15. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation.

    PubMed

    Barazzuol, Lara; Jeggo, Penny A

    2016-08-01

    The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. PMID:27125639

  16. Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats

    PubMed Central

    Ma, Jianhua; Zhang, Maoying; Li, Shaowu; Wu, Bingshan; Nie, Xiaohu; Jiao, Jiao; Zhao, Hao; Wang, Shanshan; Yang, Yuanyuan; Zhang, Yesen; Sun, Yilin; Wicha, Max S.; Chang, Alfred E.; Gao, Shaorong; Li, Qiao; Xu, Ruxiang

    2015-01-01

    Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells. PMID:26352672

  17. Dopamine release from transplanted neural stem cells in Parkinsonian rat striatum in vivo.

    PubMed

    Kang, Xinjiang; Xu, Huadong; Teng, Sasa; Zhang, Xiaoyu; Deng, Zijun; Zhou, Li; Zuo, Panli; Liu, Bing; Liu, Bin; Wu, Qihui; Wang, Li; Hu, Meiqin; Dou, Haiqiang; Liu, Wei; Zhu, Feipeng; Li, Qing; Guo, Shu; Gu, Jingli; Lei, Qian; Lü, Jing; Mu, Yu; Jin, Mu; Wang, Shirong; Jiang, Wei; Liu, Kun; Wang, Changhe; Li, Wenlin; Zhang, Kang; Zhou, Zhuan

    2014-11-01

    Embryonic stem cell-based therapies exhibit great potential for the treatment of Parkinson's disease (PD) because they can significantly rescue PD-like behaviors. However, whether the transplanted cells themselves release dopamine in vivo remains elusive. We and others have recently induced human embryonic stem cells into primitive neural stem cells (pNSCs) that are self-renewable for massive/transplantable production and can efficiently differentiate into dopamine-like neurons (pNSC-DAn) in culture. Here, we showed that after the striatal transplantation of pNSC-DAn, (i) pNSC-DAn retained tyrosine hydroxylase expression and reduced PD-like asymmetric rotation; (ii) depolarization-evoked dopamine release and reuptake were significantly rescued in the striatum both in vitro (brain slices) and in vivo, as determined jointly by microdialysis-based HPLC and electrochemical carbon fiber electrodes; and (iii) the rescued dopamine was released directly from the grafted pNSC-DAn (and not from injured original cells). Thus, pNSC-DAn grafts release and reuptake dopamine in the striatum in vivo and alleviate PD symptoms in rats, providing proof-of-concept for human clinical translation. PMID:25331880

  18. Effects of negative air ions on activity of neural substrates involved in autonomic regulation in rats

    NASA Astrophysics Data System (ADS)

    Suzuki, Satoko; Yanagita, Shinya; Amemiya, Seiichiro; Kato, Yumi; Kubota, Natsuko; Ryushi, Tomoo; Kita, Ichiro

    2008-07-01

    The neural mechanism by which negative air ions (NAI) mediate the regulation of autonomic nervous system activity is still unknown. We examined the effects of NAI on physiological responses, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV) as well as neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus (LC), nucleus ambiguus (NA), and nucleus of the solitary tract (NTS) with c-Fos immunohistochemistry in anesthetized, spontaneously breathing rats. In addition, we performed cervical vagotomy to reveal the afferent pathway involved in mediating the effects of NAI on autonomic regulation. NAI significantly decreased BP and HR, and increased HF power of the HRV spectrum. Significant decreases in c-Fos positive nuclei in the PVN and LC, and enhancement of c-Fos expression in the NA and NTS were induced by NAI. After vagotomy, these physiological and neuronal responses to NAI were not observed. These findings suggest that NAI can modulate autonomic regulation through inhibition of neuronal activity in PVN and LC as well as activation of NA neurons, and that these effects of NAI might be mediated via the vagus nerves.

  19. Classification of phthalates based on an in vitro neurosphere assay using rat mesencephalic neural stem cells.

    PubMed

    Ishido, Masami; Suzuki, Junko

    2014-02-01

    Exposure to environmental neurotoxic chemicals both in utero and during the early postnatal period can cause neurodevelopmental disorders. To evaluate the disruption of neurodevelopmental programming, we previously established an in vitro neurosphere assay system using rat mesencephalic neural stem cells that can be used to evaluate. Here, we extended the assay system to examine the neurodevelopmental toxicity of the endocrine disruptors butyl benzyl phthalate, di-n-butyl phthalate, dicyclohexyl phthalate, diethyl phthalate, di(2-ethyl hexyl) phthalate, di-n-pentyl phthalate, and dihexyl phthalate at a range of concentrations (0-100 μM). All phthalates tested inhibited cell migration with a linear or non-linear range of concentrations when comparing migration distance to the logarithm of the phthalate concentrations. On the other hand, some, but not all, phthalates decreased the number of proliferating cells. Apoptotic cells were not observed upon phthalate exposure under any of the conditions tested, whereas the dopaminergic toxin rotenone induced significant apoptosis. Thus, we were able to classify phthalate toxicity based on cell migration and cell proliferation using the in vitro neurosphere assay. PMID:24418706

  20. Effects of silver nanoparticles on human and rat embryonic neural stem cells

    PubMed Central

    Liu, Fang; Mahmood, Meena; Xu, Yang; Watanabe, Fumiya; Biris, Alexandru S.; Hansen, Deborah K.; Inselman, Amy; Casciano, Daniel; Patterson, Tucker A.; Paule, Merle G.; Slikker, William; Wang, Cheng

    2015-01-01

    Silver nano-particles (Ag-NPs) are becoming increasingly prevalent in consumer products as antibacterial agents. The increased use of Ag NP-enhanced products will almost certainly increase environmental silver levels, resulting in increased exposures and the potential for increased adverse reactions including neurotoxic effects. In the present study, embryonic neural stem cells (NSCs) from human and rat fetuses (gestational day-16) were used to determine whether Ag-NPs are capable of causing developmental neurotoxicity. The NSCs were cultured in serum free medium supplemented with appropriate growth factors. On the eighth day in vitro (DIV 8), the cells were exposed to Ag-NPs at concentrations of 1, 5, 10, and 20 μg/ml for 24 h. The cultured cells then were characterized by NSC markers including nestin and SOX2 and a variety of assays were utilized to determine the effects of Ag-NPs on NSC proliferation and viability and the underlying mechanisms associated with these effects. The results indicate that mitochondrial viability (MTT metabolism) was substantially attenuated and LDH release was increased significantly in a dose-dependent manner. Ag-NPs-induced neurotoxicity was further confirmed by up-regulated Bax protein expression, an increased number of TUNEL-positively stained cells, and elevated reactive oxygen species (ROS). NSC proliferation was also significantly decreased by Ag-NPs. Co-administration of acetyl-L-carnitine, an antioxidant agent, effectively blocked the adverse effects associated with Ag-NP exposure. PMID:25904840

  1. Experimental study on the mechanical interaction between silicon neural microprobes and rat dura mater during insertion.

    PubMed

    Fekete, Z; Németh, A; Márton, G; Ulbert, I; Pongrácz, A

    2015-02-01

    In vivo insertion experiments are essential to optimize novel neural implants. Our work focuses on the interaction between intact dura mater of rats and as-fabricated single-shaft silicon microprobes realized by deep reactive ion etching. Implantation parameters like penetration force and dimpling through intact dura mater were studied as a function of insertion speed, microprobe cross-section, tip angle and animal age. To reduce tissue resistance, we proposed a unique tip sharpening technique, which was also evaluated in in vivo insertion tests. By doubling the insertion speed (between 1.2 and 10.5 mm/min), an increase of 10-35% in penetration forces was measured. When decreasing the cross-section of the microprobes, penetration forces and dimpling was reduced by as much as 30-50% at constant insertion speeds. Force was noticed to gradually decrease by decreasing tip angles. Measured penetration forces through dura mater were reduced even down to 11±3 mN compared to unsharpened (49±13 mN) probes by utilizing our unique tip sharpening technique, which is very close to exerted penetration force in the case of retracted dura (5±1.5 mN). Our findings imply that age remarkably alters the elasticity of intact dura mater. The decreasing stiffness of dura mater results in a significant rise in penetration force and decrease in dimpling. Our work is the first in vivo comparative study on microelectrode penetration through intact and retracted dura mater. PMID:25631267

  2. Astroglial β-Arrestin1-mediated Nuclear Signaling Regulates the Expansion of Neural Precursor Cells in Adult Hippocampus

    PubMed Central

    Tao, Yezheng; Ma, Li; Liao, Zhaohui; Le, Qiumin; Yu, Jialing; Liu, Xing; Li, Haohong; Chen, Yuejun; Zheng, Ping; Yang, Zhengang; Ma, Lan

    2015-01-01

    Adult hippocampal neurogenesis is crucial for preserving normal brain function, but how it is regulated by niche cells is uncertain. Here we show that β-arrestin 1 (β-arr1) in dentate gyrus (DG) regulates neural precursor proliferation. β-arr1 knockout (KO) mice show reduced neural precursor proliferation in subgranular zone (SGZ) which could be rescued by selective viral expression of β-arr1 but not its nuclear-function-deficient mutants under control of hGFAP promotor in DG. Compared with wild type astrocytes, β-arr1 KO astrocytes nurture less neurospheres, and this may be attributed to changed activity of soluble, heat-sensitive excretive factors, such as BMP2. RNA-sequencing reveals that β-arr1 KO DG astrocytes exhibit an aberrant gene expression profile of niche factors, including elevated transcription of Bmp2. Taken together, our data suggest that β-arr1 mediated nuclear signaling regulates the production of excretive factors derived from niche astrocytes and expansion of neural precursors in DG, thus maintaining homeostasis of adult hippocampal neurogenesis. PMID:26500013

  3. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  4. Juvenile play conditions sexual partner preference in adult female rats.

    PubMed

    Paredes-Ramos, Pedro; Miquel, Marta; Manzo, Jorge; Coria-Avila, Genaro A

    2011-10-24

    Rats can display a conditioned partner preference for individuals that bear an odor previously associated with sexual reward. Herein we tested the possibility that odors associated with the reward induced by social play in prepubescent rats would induce a conditioned partner preference in adulthood. Two groups of 31-day-old, single-housed female rats were formed, and were given daily 30-min periods of social play with scented females. In one group, almond scent was paired with juvenile play during conditioning trials, whereas lemon scent functioned as a novel odor in the final test. The counterbalanced group received the opposite association. At age 42, females were tested for play partner preference with two males, one almond-scented and one lemon-scented. In both groups females displayed a play partner preference only for males scented with the paired odor. They were ovariectomized, hormone-primed, and at age 55 were tested for sexual partner preference with two scented stud males. Females displayed a sexual preference towards males scented with the paired odor as observed with more visits, solicitations, hops and darts, intromissions and ejaculations. These results indicate that olfactory stimuli paired with juvenile play affects later partner choice for play as well as for sex in female rats. PMID:21777597

  5. Development of closed-loop neural interface technology in a rat model: combining motor cortex operant conditioning with visual cortex microstimulation.

    PubMed

    Marzullo, Timothy Charles; Lehmkuhle, Mark J; Gage, Gregory J; Kipke, Daryl R

    2010-04-01

    Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices. PMID:20144922

  6. Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats

    PubMed Central

    Lozano, German; Elmaghrabi, Ayah; Salley, Jordan; Siddique, Khurrum; Gattineni, Jyothsna

    2014-01-01

    The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min−1·100 g body wt−1 in the 20% group (P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min−1·100 g body wt−1, which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min−1·100 g body wt−1). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing. PMID:25537745

  7. Neonatal Cystitis-Induced Colonic Hypersensitivity in Adult Rats: A Model of Viscero-Visceral Convergence

    PubMed Central

    Miranda, Adrian; Mickle, Aaron; Schmidt, Jamie; Zhang, Zhihong; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

    2011-01-01

    Background The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms. Methods Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days (postnatal days 14th–16th). The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissue. CRD or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-D-aspartic acid (NMDA) NR1 subunit in the L6-S1 spinal cord was examined using Western blot. Results The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan rats was significantly higher than the control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (p > 0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared to saline treated rats (p <0.05). Conclusion Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does results in overexpression of spinal NR1 subunit in adult rats. PMID:21592255

  8. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats

    PubMed Central

    Jessberger, Sebastian; Clark, Robert E.; Broadbent, Nicola J.; Clemenson, Gregory D.; Consiglio, Antonella; Lie, D. Chichung; Squire, Larry R.; Gage, Fred H.

    2009-01-01

    New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with hippocampal function used ablation strategies that were not exclusive to the hippocampus or that were associated with substantial side effects, such as inflammation. We here used a lentiviral approach to specifically block neurogenesis in the dentate gyrus of adult male rats by inhibiting WNT signaling, which is critically involved in the generation of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level-dependent effect of adult neurogenesis on the long-term retention of spatial memory in the water maze task, as rats with substantially reduced levels of newborn neurons showed less preference for the target zone in probe trials >2 wk after acquisition compared with control rats. Furthermore, animals with strongly reduced levels of neurogenesis were impaired in a hippocampus-dependent object recognition task. Social transmission of food preference, a behavioral test that also depends on hippocampal function, was not affected by knockdown of neurogenesis. Here we identified a role for newborn neurons in distinct aspects of hippocampal function that will set the ground to further elucidate, using experimental and computational strategies, the mechanism by which newborn neurons contribute to behavior. PMID:19181621

  9. Functional Myotube Formation from Adult Rat Satellite Cells in a Defined Serum-free System

    PubMed Central

    McAleer, Christopher W.; Rumsey, John W.; Stancescu, Maria; Hickman, James J.

    2016-01-01

    This manuscript describes the development of a culture system whereby mature contracting myotubes were formed from adult rat derived satellite cells. Satellite cells, extracted from the Tibialis Anterior (TA) of adult rats, were grown in defined serum-free growth and differentiation media, on a non-biological substrate, N-1[3-trimethoxysilyl propyl] diethylenetriamine. Myotubes were evaluated morphologically and immunocytochemically, using MyHC specific antibodies, as well as functionally using patch clamp electrophysiology to measure ion channel activity. Results indicated the establishment of the rapid expression of adult myosin isoforms that contrasts to their slow development in embryonic cultures. This culture system has applications in the understanding and treatment of age related muscle myopathy, muscular dystrophy, and for skeletal muscle engineering by providing a more relevant phenotype for both in vitro and in vivo applications. PMID:25683642

  10. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells.

    PubMed

    Pfenninger, Cosima V; Roschupkina, Teona; Hertwig, Falk; Kottwitz, Denise; Englund, Elisabet; Bengzon, Johan; Jacobsen, Sten Eirik; Nuber, Ulrike A

    2007-06-15

    Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133. PMID:17575139

  11. Repetitive Transcranial Magnetic Stimulation Promotes Neural Stem Cell Proliferation via the Regulation of MiR-25 in a Rat Model of Focal Cerebral Ischemia

    PubMed Central

    Zhang, Jinghui; Zhao, Xiuxiu; Lou, Jicheng; Chen, Hong; Huang, Xiaolin

    2014-01-01

    Repetitive transcranial magnetic stimulation (rTMS) has increasingly been studied over the past decade to determine whether it has a therapeutic benefit on focal cerebral ischemia. However, the underlying mechanism of rTMS in this process remains unclear. In the current study, we investigated the effects of rTMS on the proliferation of adult neural stem cells (NSCs) and explored microRNAs (miRNAs) that were affected by rTMS. Our data showed that 10 Hz rTMS significantly increased the proliferation of adult NSCs after focal cerebral ischemia in the subventricular zone (SVZ), and the expression of miR-25 was obviously up-regulated in the ischemic cortex after rTMS. p57, an identified miR-25 target gene that regulates factors linked to NSC proliferation, was also evaluated, and it exhibited down-regulation. To further verify the role of miR-25, rats were injected with a single dose of antagomir-25 and were subjected to focal cerebral ischemia followed by rTMS treatment. The results confirmed that miR-25 could be repressed specifically and could drive the up-regulation of its target gene (p57), which resulted in the inhibition of adult NSC proliferation in the SVZ after rTMS. Thus, our studies strongly indicated that 10 Hz rTMS can promote the proliferation of adult NSCs in the SVZ after focal cerebral ischemia by regulating the miR-25/p57 pathway. PMID:25302788

  12. Impairment of male reproduction in adult rats exposed to hydroxyprogesterone caproate in utero

    NASA Astrophysics Data System (ADS)

    Pushpalatha, T.; Ramachandra Reddy, P.; Sreenivasula Reddy, P.

    Hydroxyprogesterone caproate is one of the most effective and widely used drugs for the treatment of uterine bleeding and threatened miscarriage in women. Hydroxyprogesterone caproate was administered to pregnant rats in order to assess the effect of intraperitoneal exposure to supranormal levels of hydroxyprogesterone caproate on the male reproductive potential in the first generation. The cauda epididymal sperm count and motility decreased significantly in rats exposed to hydroxyprogesterone caproate during embryonic development, when compared with control rats. The levels of serum testosterone decreased with an increase in follicle stimulating hormone and luteinizing hormone in adult rats exposed to hydroxyprogesterone caproate during the embryonic stage. It was suggested that the impairment of male reproductive performance could be mediated through the inhibition of testosterone production.

  13. Effect of seven days of spaceflight on hindlimb muscle protein, RNA and DNA in adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Musacchia, X. J.

    1985-01-01

    Effects of seven days of spaceflight on skeletal muscle (soleus, gastrocnemius, EDL) content of protein, RNA and DNA were determined in adult rats. Whereas total protein contents were reduced in parallel with muscle weights, myofibrillar protein appeared to be more affected. There were no significant changes in absolute DNA contents, but a significant (P less than 0.05) increase in DNA concentration (microgram/milligram) in soleus muscles from flight rats. Absolute RNA contents were significantly (P less than 0.025) decreased in the soleus and gastrocnemius muscles of flight rats, with RNA concentrations reduced 15-30 percent. These results agree with previous ground-based observations on the suspended rat with unloaded hindlimbs and support continued use of this model.

  14. Host induction by transplanted neural stem cells in the spinal cord: further evidence for an adult spinal cord neurogenic niche

    PubMed Central

    Xu, Leyan; Mahairaki, Vasiliki; Koliatsos, Vassilis E

    2013-01-01

    Aim To explore the hypothesis that grafts of exogenous stem cells in the spinal cord of athymic rats or rats with transgenic motor neuron disease can induce endogenous stem cells and initiate intrinsic repair mechanisms that can be exploited in amyotrophic lateral sclerosis therapeutics. Materials & methods Human neural stem cells (NSCs) were transplanted into the lower lumbar spinal cord of healthy rats or rats with transgenic motor neuron disease to explore whether signals related to stem cells can initiate intrinsic repair mechanisms in normal and amyotrophic lateral sclerosis subjects. Patterns of migration and differentiation of NSCs in the gray and white matter, with emphasis on the central canal region and ependymal cell-driven neurogenesis, were analyzed. Results Findings suggest that there is extensive cross-signaling between transplanted NSCs and a putative neurogenic niche in the ependyma of the lower lumbar cord. The formation of a neuronal cord from NSC-derived cells next to ependyma suggests that this structure may serve a mediating or auxiliary role for ependymal induction. Conclusion These findings raise the possibility that NSCs may stimulate endogenous neurogenesis and initiate intrinsic repair mechanisms in the lower spinal cord. PMID:23164079

  15. Mechanism of Forelimb Motor Function Restoration after Cervical Spinal Cord Hemisection in Rats: A Comparison of Juveniles and Adults

    PubMed Central

    Hasegawa, Atsushi; Takahashi, Masahito; Satomi, Kazuhiko; Ohne, Hideaki; Takeuchi, Takumi; Sato, Shunsuke; Ichimura, Shoichi

    2016-01-01

    The aim of this study was to investigate forelimb motor function after cervical spinal cord injury in juvenile and adult rats. Both rats received a left segmental hemisection of the spinal cord after C3-C4 laminectomy. Behavioral evaluation of motor function was monitored and assessed using the New Rating Scale (NRS) and Forelimb Locomotor Scale (FLS) and by measuring the range of motion (ROM) of both the elbow and wrist. Complete left forelimb motor paralysis was observed in both rats. The NRS showed motor function recovery restored to 50.2 ± 24.7% in juvenile rats and 34.0 ± 19.8% in adult rats. FLS was 60.4 ± 26.8% in juvenile rats and 46.5 ± 26.9% in adult rats. ROM of the elbow and wrist were 88.9 ± 20.6% and 44.4 ± 24.1% in juvenile rats and 70.0 ± 29.2% and 40.0 ± 21.1% in adult rats. Thus, the NRS and ROM of the elbow showed a significant difference between age groups. These results indicate that left hemisection of the cervical spinal cord was not related to right-sided motor functions. Moreover, while motor paralysis of the left forelimb gradually recovered in both groups, the improvement was greater in juvenile rats. PMID:27065569

  16. Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia.

    PubMed

    Tan, S; Zhi, P K; Luo, Z K; Shi, J

    2015-09-10

    Accumulated evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to stroke outcome. However, it is unclear whether hyperglycemia, which is frequently tested positive in patients with acute ischemic stroke, influences stroke-induced neurogenesis. The aim of the present study is to examine the effect of hyperglycemia on stroke-induced neurogenesis in a rat model of transient focal cerebral ischemia. For this purpose, adult male Sprague-Dawley rats (220-250 g) were subjected to 90 min of middle cerebral artery occlusion (MCAO). Glucose was administered during ischemia to produce target blood levels ranging from 4.83 ± 0.94 mM (normoglycemia) to 20.76 ± 1.56 mM. To label proliferating cells in ischemic ipsilateral subventricular zone (SVZ) of lateral ventricles, 5'-bromo-2'-deoxyuridine (BrdU) was injected 24h after MCAO. Brains were harvested 2h post-BrdU to evaluate the effects of hyperglycemia on infarct volume and SVZ cell proliferation. Rats that were severely hyperglycemic (19.26 ± 1.48 mM to 20.76 ± 1.56 mM) during ischemia had 24.26% increase in infarct volume (P<0.05) and more serious neurological function deficits (P<0.05). The severe hyperglycemic rats also showed dramatically decreased proliferation of neural stem/progenitor cells (NSPCs) (P<0.05) and down-regulation of the phosphorylation of cyclic-AMP response element-binding protein (pCREB) (P<0.05)and brain-derived neurotrophic factor (BDNF) (P<0.05) in ipsilateral SVZ. But the above-mentioned detrimental effects were not observed in rats that were rendered with mild hyperglycemia (9.43 ± 1.39-10.13 ± 1.24 mM). Our findings indicate that severe instead of mild hyperglycemia exacerbates ischemic injury and inhibits stroke-induced SVZ neurogenesis by a mechanism involving suppression of CREB and BDNF signaling. PMID:26126927

  17. Low Dose Parathyroid Hormone Maintains Normal Bone Formation in Adult Male Rats During Rapid Weight Loss

    PubMed Central

    Turner, Russell T.; Iwaniec, Urszula T.

    2011-01-01

    A persistent negative energy balance results in bone loss. It is not clear whether the bone loss associated with chronic negative energy balance can be prevented. The objective of this study was to assess the efficacy of intermittent low dose parathyroid hormone (PTH) treatment in maintaining normal bone formation during severe energy restriction. Six-month-old male Fisher 344 rats were divided into 4 treatment groups: (1) baseline, (2) ad libitum (ad lib)-fed control, (3) energy-restricted (to consume 40% ad lib caloric intake), or (4) energy-restricted + low dose (1 μg/kg/d) PTH. Severe energy restriction for 14 days decreased body weight and serum leptin levels. Compared to ad lib-fed controls, energy-restricted rats had lower cancellous bone formation, higher osteoclast perimeter/bone perimeter and higher bone marrow adiposity in the proximal tibial metaphysis. Also, the energy-restricted rats had a lower periosteal bone formation rate at the tibia-fibula synostosis. Administration of PTH to energy-restricted rats had no effect on weight loss or osteoclast perimeter/bone perimeter. In contrast, energy-restricted rats treated with PTH had higher rates of cancellous and cortical bone formation compared to energy-restricted rats, and did not differ from the ad lib-fed control animals. Furthermore, PTH treatment maintained normal bone marrow adiposity. In conclusion, rapid weight loss in adult male rats was accompanied by decreased bone formation and increased bone marrow adiposity and these changes were prevented by low dose PTH treatment. Taken together, the results suggest that the energy cost of bone formation in adult rats is low and PTH therapy is effective in preventing the reduced bone formation associated with rapid weight loss. PMID:21215827

  18. Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats

    PubMed Central

    Boonnate, Piyanard; Waraasawapati, Sakda; Hipkaeo, Wiphawi; Pethlert, Supattra; Sharma, Amod; Selmi, Carlo; Prasongwattana, Vitoon; Cha’on, Ubon

    2015-01-01

    Background The amount of dietary monosodium glutamate (MSG) is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology. Methods Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group). All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT) were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets. Results MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated. Conclusion Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account. PMID:26121281

  19. Gene Expression Profile of Adult Human Olfactory Bulb and Embryonic Neural Stem Cell Suggests Distinct Signaling Pathways and Epigenetic Control

    PubMed Central

    Marei, Hany E. S.; Ahmed, Abd-Elmaksoud; Michetti, Fabrizio; Pescatori, Mario; Pallini, Roberto; Casalbore, Patricia; Cenciarelli, Carlo; Elhadidy, Mohamed

    2012-01-01

    Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults. PMID:22485144

  20. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity. PMID:18679812

  1. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression.

    PubMed

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V; Christiansen, Sofie; Christensen, Trine; Andreasen, Jesper T; Palme, Rupert; Lichota, Jacek; Wiborg, Ove

    2012-12-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant tendency towards higher total cytosine methylation in rats from low maternal care dams. Assessment of methylation in the resilient versus anhedonic-like rat phenotypes, revealed only minor differences. Thus, maternal care status seems to be a strong predictor or trait marker for the behavioural phenotype. PMID:23075705

  2. Comparison of skull and femur lead levels in adult rats

    SciTech Connect

    Denton, J.E.; Potter, G.D.; Santolucito, J.A.

    1980-12-01

    The purpose of the study was to elucidate the relationship between skull and femur lead levels in laboratory rats. Forty-eight female rats were given one of four lead chloride drinking water solutions: 0.05, 0.58, 17, or 352 ppM lead. Two animals from each group were sacrificed after 3, 6, 9, 12, 15, and 24 weeks of treatment. Both femurs and the frontal and parietal bones of the skull were removed from each animal and analyzed for lead concentration by atomic absorption spectroscopy. A significant accumulation of lead was observed in femurs and skull bones only from animals in the 352 ppM lead treatment group. The lead concentrations of the femurs were significantly higher than skull lead concentrations for all groups and this relationship was described using a linear regression equation.

  3. Experimental study of vein subvolution combined with neural stem cells to repair sciatic neurologic defects in rats

    PubMed Central

    Li, Kang; Jiang, Yan; Jiang, Dianming

    2015-01-01

    This study aims to explore the effects of vein subvolution combined with neural stem cells on nerve regeneration. Animal model of sciatic nerve defects was established with SD rats. A total of 63 SD rats were divided into control group, vein subvolution group (treatment 1 group) and vein subvolution combined with neural stem cells group (treatment 2 group). The recovery of neurological function after 12 weeks was evaluated by nerve electrophysiological technique, histological observation and other methods. The recovery degree of sciatic nerve defect in treatment 2 group was better than that of other groups; The SFI values significantly decreased in treatment 2 group after 8 weeks; the regenerative nerve fiber numbers in treatment 2 group were significant higher than that of other groups; the recovery rates of treatment 1 and 2 groups were significant higher than that of control group. The effects of vein subvolution combined with neural stem cells on repairing peripheral nerve defects were better than that of vein subvolution method. PMID:26617811

  4. Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task

    PubMed Central

    van Duuren, Esther; Escámez, Francisco A. Nieto; Joosten, Ruud N.J.M.A.; Visser, Rein; Mulder, Antonius B.; Pennartz, Cyriel M.A.

    2007-01-01

    The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory discrimination “go”/“no-go” task in which five different odor stimuli were predictive for various amounts of reward or an aversive reinforcer. Neural correlates related to both actual and expected reward magnitude were observed. Responses related to reward expectation occurred during the execution of the behavioral response toward the reward site and within a waiting period prior to reinforcement delivery. About one-half of these neurons demonstrated differential firing toward the different reward sizes. These data provide new and strong evidence that reward expectancy, regardless of reward magnitude, is coded by neurons of the rat OBFc, and are indicative for representation of quantitative information concerning expected reward. Moreover, neural correlates of reward expectancy appear to be distributed across both motor and nonmotor phases of the task. PMID:17562896

  5. 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.

  6. Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation

    SciTech Connect

    Norton, S.

    1986-04-01

    Seven behavioral tests were used to evaluate the postnatal behavior of rats after exposure on gestational Day 15 to 0, 25, 50, 75, or 125 r, whole body irradiation of the pregnant rat. Three tests were administered in the first 2 postnatal weeks (righting reflex, negative geotaxis, and reflex suspension); three tests were administered on postnatal Day 21 (modified open field, spatial maze, and continuous corridor). As adults, the rats were retested with the same tests as at 21 days and also in the running wheel. Dose-response decreases in body weight were greater in the younger rats. Some behavioral tests were not altered by irradiation, while others showed clear dose-response relationships, starting as low as 25 r. The early changes were characterized by light body weight, delays in behavioral development and hypoactivity, followed by recovery of some parameters with maturation. Eventually hyperactivity developed in adult rats after gestational irradiation. However, it cannot be concluded that either morphological or behavioral tests are more sensitive than neonatal body weight change for detection of damage from gestational irradiation.

  7. Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

    PubMed

    Slamberová, Romana; Schutová, Barbora; Hrubá, Lenka; Pometlová, Marie

    2011-10-10

    Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test. PMID:21645557

  8. Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification

    PubMed Central

    Stergiopoulos, Athanasios; Elkouris, Maximilianos; Politis, Panagiotis K.

    2015-01-01

    Over the last decades, adult neurogenesis in the central nervous system (CNS) has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG) of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation vs. differentiation decisions of neural stem cells (NSCs), promoting cell cycle exit and neuronal differentiation, while inhibiting astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs), differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis. PMID:25674048

  9. Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification.

    PubMed

    Stergiopoulos, Athanasios; Elkouris, Maximilianos; Politis, Panagiotis K

    2014-01-01

    Over the last decades, adult neurogenesis in the central nervous system (CNS) has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG) of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation vs. differentiation decisions of neural stem cells (NSCs), promoting cell cycle exit and neuronal differentiation, while inhibiting astrogliogenesis. During the complex differentiation events in adult hippocampal neurogenesis, Prox1 is required for maintenance of intermediate progenitors (IPs), differentiation and maturation of glutamatergic interneurons, as well as specification of DG cell identity over CA3 pyramidal fate. The mechanism by which Prox1 exerts multiple functions involves distinct signaling pathways currently not fully highlighted. In this mini-review, we thoroughly discuss the Prox1-dependent phenotypes and molecular pathways in adult neurogenesis in relation to different upstream signaling cues and cell fate determinants. In addition, we discuss the possibility that Prox1 may act as a cross-talk point between diverse signaling cascades to achieve specific outcomes during adult neurogenesis. PMID:25674048

  10. Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats.

    PubMed

    Bourke, Chase H; Stowe, Zachary N; Neigh, Gretchen N; Olson, Darin E; Owens, Michael J

    2013-01-01

    Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague-Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10-20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication. PMID:23906943

  11. TESTOSTERONE AND SOCIAL ISOLATION INFLUENCE ADULT NEUROGENESIS IN THE DENTATE GYRUS OF MALE RATS

    PubMed Central

    Spritzer, Mark D.; Ibler, Erin; Inglis, William; Curtis, Molly G.

    2011-01-01

    Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): 1) sham/pair-housed, 2) sham/isolated, 3) castrate/pair-housed, and 4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n =8/group): 1) oil/pair-housed, 2) oil/isolated, 3) testosterone/pair-housed, and 4) testosterone/isolated. All rats were injected with 5-Bromo-2’-deoxyuridine (BrdU, 200 mg/kg body mass) and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and sub-granular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating levels of

  12. Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats.

    PubMed

    Spritzer, M D; Ibler, E; Inglis, W; Curtis, M G

    2011-11-10

    Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): (1) sham/pair-housed, (2) sham/isolated, (3) castrate/pair-housed, and (4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated, and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n=8/group): (1) oil/pair-housed, (2) oil/isolated, (3) testosterone/pair-housed, and (4) testosterone/isolated. All rats were injected with 5-bromo-2'-deoxyuridine (BrdU, 200 mg/kg body mass), and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and subgranular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating

  13. Sensory Neural Responses to Ozone Exposure during Early Postnatal Development in Rat Airways

    PubMed Central

    Hunter, Dawn D.; Wu, Zhongxin; Dey, Richard D.

    2010-01-01

    Airway infections or irritant exposures during early postnatal periods may contribute to the onset of childhood asthma. The purpose of this study was to examine critical periods of postnatal airway development during which ozone (O3) exposure leads to heightened neural responses. Rats were exposed to O3 (2 ppm) or filtered air for 1 hour on specific postnatal days (PDs) between PD1 and PD29, and killed 24 hours after exposure. In a second experiment, rats were exposed to O3 on PD2–PD6, inside a proposed critical period of development, or on PD19–PD23, outside the critical period. Both groups were re-exposed to O3 on PD28, and killed 24 hours later. Airways were removed, fixed, and prepared for substance P (SP) immunocytochemistry. SP nerve fiber density (NFD) in control extrapulmonary (EXP) epithelium/lamina propria (EPLP) increased threefold, from 1% to 3.3% from PD1–PD3 through PD13–PD15, and maintained through PD29. Upon O3 exposure, SP-NFD in EXP–smooth muscle (SM) and intrapulmonary (INT)-SM increased at least twofold at PD1–PD3 through PD13–PD15 in comparison to air exposure. No change was observed at PD21–PD22 or PD28–PD29. In critical period studies, SP-NFD in the INT-SM and EXP-SM of the PD2–PD6 O3 group re-exposed to O3 on PD28 was significantly higher than that of the group exposed at PD19–PD23 and re-exposed at PD28. These findings suggest that O3-mediated changes in sensory innervation of SM are more responsive during earlier postnatal development. Enhanced responsiveness of airway sensory nerves may be a contributing mechanism of increased susceptibility to environmental exposures observed in human infants and children. PMID:20118220

  14. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    PubMed

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

  15. Peri-pubertal exposure to testicular hormones organizes response to novel environments and social behaviour in adult male rats

    PubMed Central

    Brown, Gillian R.; Kulbarsh, Kyle D.; Spencer, Karen A.; Duval, Camille

    2015-01-01

    Previous research has shown that exposure to testicular hormones during the peri-pubertal period of life has long-term, organizational effects on adult sexual behaviour and underlying neural mechanisms in laboratory rodents. However, the organizational effects of peri-pubertal testicular hormones on other aspects of behaviour and brain function are less well understood. Here, we investigated the effects of manipulating peri-pubertal testicular hormone exposure on later behavioural responses to novel environments and on hormone receptors in various brain regions that are involved in response to novelty. Male rodents generally spend less time in the exposed areas of novel environments than females, and this sex difference emerges during the peri-pubertal period. Male Lister-hooded rats (Rattus norvegicus) were castrated either before puberty or after puberty, then tested in three novel environments (elevated plus-maze, light–dark box, open field) and in an object/social novelty task in adulthood. Androgen receptor (AR), oestrogen receptor (ER1) and corticotropin-releasing factor receptor (CRF-R2) mRNA expression were quantified in the hypothalamus, hippocampus and medial amygdala. The results showed that pre-pubertally castrated males spent more time in the exposed areas of the elevated-plus maze and light–dark box than post-pubertally castrated males, and also confirmed that peri-pubertal hormone exposure influences later response to an opposite-sex conspecific. Hormone receptor gene expression levels did not differ between pre-pubertally and post-pubertally castrated males in any of the brain regions examined. This study therefore demonstrates that testicular hormone exposure during the peri-pubertal period masculinizes later response to novel environments, although the neural mechanisms remain to be fully elucidated. PMID:26159287

  16. Neural pathways that mediate the effects of afferent stimuli on paraventricular nucleus multiunit activity in freely moving rats.

    PubMed

    Mor, G; Saphier, D; Feldman, S

    1987-01-01

    The direct involvement of the hypothalamic paraventricular nucleus (PVN) in the control of adrenocortical secretion is now generally accepted. In order to contribute to our understanding of the electrical activity of cells in this region during adrenocortical activation, we have recorded multiunit electrical activity (MUA) in response to acute neural stimuli in freely moving male rats and have examined the pathways involved. Photic, acoustic, olfactory, and sciatic nerve stimulation all increased PVN MUA by between 130% and 250%. These responses were selectively blocked, according to the stimulus modality tested, by radiofrequency lesions of central neural structures. Thus PVN responses to photic stimulation were blocked by lesions of the suprachiasmatic nuclei and reduced by mammillary peduncle lesions but were unaffected by lesions of the bed nuclei of the stria terminalis. Responses to acoustic stimulation were blocked by lesions of the mammillary peduncles but not by those placed in the suprachiasmatic nuclei, the septum, or the bed nuclei of the stria terminalis. Lesions of the septum blocked the response to sciatic nerve stimulation but did not affect the response to olfactory stimulation with amyl acetate fumes, which was blocked by lesions of the bed nuclei of the stria terminalis. The data confirm those obtained in endocrine studies concerning the neural pathways involved in the transmission of neural stimuli that produce adrenocortical activation. PMID:3625806

  17. Testosterone influences spatial strategy preferences among adult male rats

    PubMed Central

    Spritzer, Mark D.; Fox, Elliott C.; Larsen, Gregory D.; Batson, Christopher G.; Wagner, Benjamin A.; Maher, Jack

    2013-01-01

    Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats’ strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent. PMID:23597827

  18. B-cell production and differentiation in adult rats.

    PubMed Central

    Bazin, H; Platteau, B; Maclennan, I C; Johnson, G D

    1985-01-01

    The B-cell development in a group of rats was suppressed for the first 45 days of life by serial administration of rabbit anti-rat IgM and IgD antibody. Total or near total suppression of B lymphopoiesis was achieved. At 45 days, suppression was stopped by injection of IgM and IgD rat paraproteins. The sequence of B-cell and plasma cell development following suppression was assessed by immunohistological analysis of spleen lymph nodes and small intestinal lamina propria. The main findings are listed below. Complete reconstitution of B-cell numbers occurs within 8 days, at which stage germinal centres are also present. B lymphopoiesis in the red pulp of the spleen differs from that reported for bone marrow. Cells develop expressing surface sIgM and sIgM with IgA, but not sIgD. sIgD-positive cells first appear in splenic follicles 2 days after stopping suppression, but their appearance in lymph nodes is delayed until after 3 days. At this stage, sIgD-positive cells become apparent in the splenic red pulp. IgM plasma cells appear from day 4. IgA plasma cells in the gut appear in small numbers at day 6, and gradually increase to normal numbers by day 14. sIgG2c expression in the splenic marginal zone did not approach normal levels, even 2 weeks after suppression was stopped. Images Figure 4 Figure 2 Figure 3 PMID:3871730

  19. Neural correlates of time-varying functional connectivity in the rat

    PubMed Central

    Thompson, Garth John; Merritt, Michael Donelyn; Pan, Wen-Ju; Magnuson, Matthew Evan; Grooms, Joshua Koehler; Jaeger, Dieter; Keilholz, Shella Dawn

    2013-01-01

    Functional connectivity between brain regions, measured with resting state functional magnetic resonance imaging, holds great potential for understanding the basis of behavior and neuropsychiatric diseases. Recently it has become clear that correlations between the blood oxygenation level dependent (BOLD) signals from different areas vary over the course of a typical scan (6–10 minutes in length), though the changes are obscured by standard methods of analysis that assume the relationships are stationary. Unfortunately, because similar variability is observed in signals that share no temporal information, it is unclear which dynamic changes are related to underlying neural events. To examine this question, BOLD data were recorded simultaneously with local field potentials (LFP) from interhemispheric primary somatosensory cortex (SI) in anesthetized rats. LFP signals were converted into band-limited power (BLP) signals including delta, theta, alpha, beta and gamma. Correlation between signals from interhemispheric SI was performed in sliding windows to produce signals of correlation over time for BOLD and each BLP band. Both BOLD and BLP signals showed large changes in correlation over time and the changes in BOLD were significantly correlated to the changes in BLP. The strongest relationship was seen when using the theta, beta and gamma bands. Interestingly, while steady-state BOLD and BLP correlate with the global fMRI signal, dynamic BOLD becomes more like dynamic BLP after the global signal is regressed. As BOLD sliding window connectivity is partially reflecting underlying LFP changes, the present study suggests it may be a valuable method of studying dynamic changes in brain states. PMID:23876248

  20. Pulsed infrared light alters neural activity in rat somatosensory cortex in vivo.

    PubMed

    Cayce, Jonathan M; Friedman, Robert M; Jansen, E Duco; Mahavaden-Jansen, Anita; Roe, Anna W

    2011-07-01

    Pulsed infrared light has shown promise as an alternative to electrical stimulation in applications where contact free or high spatial precision stimulation is desired. Infrared neural stimulation (INS) is well characterized in the peripheral nervous system; however, to date, research has been limited in the central nervous system. In this study, pulsed infrared light (λ=1.875 μm, pulse width=250 μs, radiant exposure=0.01-0.55 J/cm(2), fiber size=400 μm, repetition rate=50-200 Hz) was used to stimulate the somatosensory cortex of anesthetized rats, and its efficacy was assessed using intrinsic optical imaging and electrophysiology techniques. INS was found to evoke an intrinsic response of similar magnitude to that evoked by tactile stimulation (0.3-0.4% change in intrinsic signal magnitude). A maximum deflection in the intrinsic signal was measured to range from 0.05% to 0.4% in response to INS, and the activated region of cortex measured approximately 2mm in diameter. The intrinsic signal magnitude increased with faster laser repetition rates and increasing radiant exposures. Single unit recordings indicated a statistically significant decrease in neuronal firing that was observed at the onset of INS stimulation (0.5s stimulus) and continued up to 1s after stimulation onset. The pattern of neuronal firing differed from that observed during tactile stimulation, potentially due to a different spatial integration field of the pulsed infrared light compared to tactile stimulation. The results demonstrate that INS can be used safely and effectively to manipulate neuronal firing. PMID:21513806

  1. Developmental features of rat cerebellar neural cells cultured in a chemically defined medium

    SciTech Connect

    Gallo, V.; Ciotti, M.T.; Aloisi, F.; Levi, G.

    1986-01-01

    We studied some aspects of the differentiation of rat cerebellar neural cells obtained from 8-day postnatal animals and cultured in a serum-free, chemically defined medium (CDM). The ability of the cells to take up radioactive transmitter amino acids was analyzed autoradiographically. The L-glutamate analogue /sup 3/H-D-aspartate was taken up by astroglial cells, but not by granule neurons, even in late cultures (20 days in vitro). This is in agreement with the lack of depolarization-induced release of /sup 3/H-D-aspartate previously observed in this type of culture. In contrast, /sup 3/H-(GABA) was scarcely accumulated by glial-fibrillary-acidic-protein (GFAP)-positive astrocytes, but taken up by glutamate-decarboxylase-positive inhibitory interneurons and was released in a Ca2+-dependent way upon depolarization: /sup 3/H-GABA evoked release progressively increased with time in culture. Interestingly, the expression of the vesicle-associated protein synapsin I was much reduced in granule cells cultured in CDM as compared to those maintained in the presence of serum. These data would indicate that in CDM the differentiation of granule neurons is not complete, while that of GABAergic neurons is not greatly affected. Whether the diminished differentiation of granule cells must be attributed only to serum deprivation or also to other differences in the composition of the culture medium remains to be established. /sup 3/H-GABA was avidly taken up also by a population of cells which were not recognized by antibodies raised against GFAP, glutamate decarboxylase, and microtubule-associated protein 2. These cells have been characterized as bipotential precursors of oligodendrocytes and of a subpopulation of astrocytes bearing a stellate shape and capable of high-affinity /sup 3/H-GABA uptake.

  2. Programming Hippocampal Neural Stem/Progenitor Cells into Oligodendrocytes Enhances Remyelination in the Adult Brain after Injury.

    PubMed

    Braun, Simon M G; Pilz, Gregor-Alexander; Machado, Raquel A C; Moss, Jonathan; Becher, Burkhard; Toni, Nicolas; Jessberger, Sebastian

    2015-06-23

    Demyelinating diseases are characterized by a loss of oligodendrocytes leading to axonal degeneration and impaired brain function. Current strategies used for the treatment of demyelinating disease such as multiple sclerosis largely rely on modulation of the immune system. Only limited treatment options are available for treating the later stages of the disease, and these treatments require regenerative therapies to ameliorate the consequences of oligodendrocyte loss and axonal impairment. Directed differentiation of adult hippocampal neural stem/progenitor cells (NSPCs) into oligodendrocytes may represent an endogenous source of glial cells for cell-replacement strategies aiming to treat demyelinating disease. Here, we show that Ascl1-mediated conversion of hippocampal NSPCs into mature oligodendrocytes enhances remyelination in a diphtheria-toxin (DT)-inducible, genetic model for demyelination. These findings highlight the potential of targeting hippocampal NSPCs for the treatment of demyelinated lesions in the adult brain. PMID:26074082

  3. Maternal Undernutrition Induces Premature Reproductive Senescence in Adult Female Rat Offspring

    PubMed Central

    Khorram, Omid; Keen-Rinehart, Erin; Chuang, Tsai-Der; Ross, Michael G.; Desai, Mina

    2014-01-01

    Objective To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring. Design Animal (rat) study. Setting Research Laboratory. Animals Female Sprague-Dawley rats. Intervention(s) Food restriction during the second half of pregnancy in rats. Main Outcome Measures Circulating gonadotropins, Anti-Mullerian Hormone (AMH), ovarian morphology, estrous cyclicity and gene expression studies in the hypothalamus and ovary in 1 day old (P1) and aging adult offspring. Results Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating testosterone (T), increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma Leuteinizing (LH/)/Follicle Stimulating hormone (FSH) levels, reduced estradiol (E2) levels and no changes in AMH in adult LBW offspring compared to control offspring. Hypothalamic expression of leptin receptor (OBRb), estrogen receptor-α (ER-α) and Gonadotropin Releasing hormone (GnRH) protein were altered in an age-dependent manner with increased ObRb, ER-α expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami. Conclusion Our data indicates that the maternal nutritional environment programs reproductive potential of the offspring through alteration of the hypothalamic-pituitary-gonadal axis. The premature reproductive senescence in LBW offspring could be secondary to development of obesity and hyperleptinemia in these animals in adult life. PMID:25439841

  4. Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats.

    PubMed

    Gellner, Candice A; Belluzzi, James D; Leslie, Frances M

    2016-10-01

    Although smoking initiation typically occurs during adolescence, most preclinical studies of tobacco use involve adult animals. Furthermore, their focus is largely on nicotine alone, even though cigarette smoke contains thousands of constituents. The present study therefore aimed to determine whether aqueous constituents in cigarette smoke affect acquisition of nicotine self-administration during adolescence in rats. Adolescent and adult male rats, aged postnatal day (P) 25 and 85, respectively, were food trained on a fixed ratio 1 (FR1) schedule, then allowed to self-administer one of 5 doses of nicotine (0, 3.75, 7.5, 15, or 30 μg/kg) or aqueous cigarette smoke extract (CSE) with equivalent nicotine content. Three progressively more difficult schedules of reinforcement, FR1, FR2, and FR5, were used. Both adolescent and adult rats acquired self-administration of nicotine and CSE. Nicotine and CSE similarly increased non-reinforced responding in adolescents, leading to enhanced overall drug intake as compared to adults. When data were corrected for age-dependent alterations in non-reinforced responding, adolescents responded more for low doses of nicotine and CSE than adults at the FR1 reinforcement schedule. No differences in adolescent responding for the two drugs were seen at this schedule, whereas adults had fewer responses for CSE than for nicotine. However, when the reinforcement schedule was increased to FR5, animals dose-dependently self-administered both nicotine and CSE, but no drug or age differences were observed. These data suggest that non-nicotine tobacco smoke constituents do not influence the reinforcing effect of nicotine in adolescents. PMID:27346207

  5. DISTRIBUTION OF [14C]ETHANE DIMENTHANESULFONATE IN IMMATURE AND ADULT MALE RATS FOLLOWING AN ACUTE EXPOSURE

    EPA Science Inventory

    In the adult rat, ethane dimethanesulphonate (EDS) reduces testosterone (T) production by killing Leydig cells. Studies have also shown that acute EDS administration produces transient infertility and epididymal effects. Although these later effects were believed to be indirect r...

  6. Resveratrol improves reproductive parameters of adult rats varicocelized in peripuberty.

    PubMed

    Mendes, Talita Biude; Paccola, Camila Cicconi; de Oliveira Neves, Flávia Macedo; Simas, Joana Noguères; da Costa Vaz, André; Cabral, Regina Elisabeth L; Vendramini, Vanessa; Miraglia, Sandra Maria

    2016-07-01

    The aim of this study was to investigate the protective action of resveratrol against the reproductive damage caused by left-sided experimental varicocele. There was a reduction of testicular major axis in the varicocele group when compared with the other groups; the testicular volume was reduced in varicocele group in comparison to the sham-control and resveratrol groups. The frequency of morphologically abnormal sperm was higher in varicocele and varicocele treated with resveratrol groups than in sham-control and resveratrol groups. The frequency of sperm with 100% of mitochondrial activity and normal acrosome integrity were lower in varicocele group than in varicocele treated with resveratrol, sham-control and resveratrol groups. Sperm motility was also reduced in varicocele group than in other groups. The sperm DNA fragmentation was higher in varicocele group than in other groups. Testicular levels of malondialdehyde were higher in varicocele and varicocele treated with resveratrol groups. The varicocele and varicocele treated with resveratrol groups had a significantly higher frequency of TUNEL-positive cells than sham-control and resveratrol groups; however, immunolabeling of the testes from varicocele treated with resveratrol group showed a lower number of apoptotic germ cells in comparison with the left testis of rats of the varicocele group. Reproductive alterations produced by varicocele from peripuberty were reduced by resveratrol in adulthood. Resveratrol should be better investigated as an adjuvant in the treatment of varicocele. Daily administration of resveratrol to rats with varicocele from peripuberty improves sperm quality in the adulthood. PMID:27069006

  7. Effect of dietary caffeine and theophylline on urinary calcium excretion in the adult rat.

    PubMed

    Whiting, S J; Whitney, H L

    1987-07-01

    The chronic effects of dietary caffeine or theophylline on urinary calcium excretion were investigated in the adult male rat. When caffeine was added at two concentrations, 0.75 and 1.50 g/kg diet, 24-h urinary calcium excretion rose 300 and 450% on d 7, and 200 and 330% on d 14, respectively. There were no changes in the 24-h urinary excretion of phosphate, sulfate, sodium and cAMP nor did urine volume change. The high dose of caffeine was compared to an equimolar dose of theophylline (1.39 g/kg diet) in both Wistar and Sprague-Dawley rats. Urinary calcium excretion in theophylline-treated rats was significantly greater than in caffeine-treated rats on all sampling days and in both strains of rat; the calciuric effect lasted at least 22 d. When rats were given indomethacin (3.3 mg/kg diet) the calciuria induced by caffeine and theophylline was abolished, and sodium excretion in all groups was reduced by 35-50%, but urine volume was unchanged. The calciuria of methylxanthine feeding may result from a prostaglandin-mediated process distinct from diuresis. PMID:3612301

  8. Horizontal Ladder Task-Specific Re-training in Adult Rats with Contusive Thoracic Spinal Cord Injury

    PubMed Central

    Onifer, Stephen M.; Zhang, Oliver; Whitnel-Smith, Laura K.; Raza, Kashif; O'Dell, Christopher R.; Lyttle, Travis S.; Rabchevsky, Alexander G.; Kitzman, Patrick H.; Burke, Darlene A.

    2012-01-01

    Purpose Using the horizontal ladder task, we examined some issues that need to be resolved before task-specific rehabilitative training can be employed clinically for the frequent contusive spinal cord injury (SCI). We hypothesized that improving recovery in task performance after contusive thoracic SCI requires frequent re-training and initiating the re-training early during spontaneous recovery. Methods Contusive SCI was produced at the adult female Sprague Dawley rat T10 vertebra. Task re-training was initiated one week later when occasional weight-supported plantar steps were taken overground (n=8). It consisted of 2 repetitions each day, 5 days each week, for 3 weeks. Task performance and overground locomotion were assessed weekly. Neurotransmission through the SCI ventrolateral funiculus was examined. SCI morphometry was determined. Results Re-training did not improve task performance recovery compared to untrained Controls (n=7). Untrained overground locomotion and neurotransmission through the SCI did not change. Lesion area at the injury epicenter as a percentage of the total spinal cord area as well as total tissue, lesion, and spared tissue, white matter, or gray matter volumes did not differ. Conclusions For the horizontal ladder task after contusive thoracic SCI, earlier re-training sessions with more repetitions and critical neural circuitry may be necessary to engender a rehabilitation effect. PMID:21697591

  9. As Working Memory Grows: A Developmental Account of Neural Bases of Working Memory Capacity in 5- to 8-Year Old Children and Adults.

    PubMed

    Kharitonova, Maria; Winter, Warren; Sheridan, Margaret A

    2015-09-01

    Working memory develops slowly: Even by age 8, children are able to maintain only half the number of items that adults can remember. Neural substrates that support performance on working memory tasks also have a slow developmental trajectory and typically activate to a lesser extent in children, relative to adults. Little is known about why younger participants elicit less neural activation. This may be due to maturational differences, differences in behavioral performance, or both. Here we investigate the neural correlates of working memory capacity in children (ages 5-8) and adults using a visual working memory task with parametrically increasing loads (from one to four items) using fMRI. This task allowed us to estimate working memory capacity limit for each group. We found that both age groups increased the activation of frontoparietal networks with increasing working memory loads, until working memory capacity was reached. Because children's working memory capacity limit was half of that for adults, the plateau occurred at lower loads for children. Had a parametric increase in load not been used, this would have given an impression of less activation overall and less load-dependent activation for children relative to adults. Our findings suggest that young children and adults recruit similar frontoparietal networks at working memory loads that do not exceed capacity and highlight the need to consider behavioral performance differences when interpreting developmental differences in neural activation. PMID:25961641

  10. Effect of the antioxidant dibunol on adrenocortical, thyroid, and adenohypopyseal function in adult and old rats

    SciTech Connect

    Gorban', E.N.

    1986-04-01

    This paper studies the effect of dibunol (4-methyl-2,6-di-tert-butylphenol) (D) on the function of the adrenal cortex, thyroid gland, and adenhypophysis, which produces trophic hormones for the other two glands. Experiments were carried out on adult rats. After injection of D concentrations of corticosterone (CS), triodothyronine (T/sub 3/), ACTH, and thyrotrophin (TSH) in the blood plasma and the CS concentration in tssue of the adenohypophysis were determined. It is shown that injection of D caused biphasic changes in the CS concentration in both tissues studied in adult and old animals.

  11. Effects of 4-Vinylcyclohexene Diepoxide on Peripubertal and Adult Sprague–Dawley Rats: Ovarian, Clinical, and Pathologic Outcomes

    PubMed Central

    Muhammad, F Salih; Goode, Amanda K; Kock, Nancy D; Arifin, Esther A; Cline, J Mark; Adams, Michael R; Hoyer, Patricia B; Christian, Patricia J; Isom, Scott; Kaplan, Jay R; Appt, Susan E

    2009-01-01

    Young rats treated daily with intraperitoneal 4-vinylcyclohexene diepoxide (VCD) undergo selective destruction of primordial follicles, resulting in gradual ovarian failure resembling the menopausal transition in women. To determine whether VCD has similar effects on ovaries of older rats, adult and peripubertal Sprague–Dawley rats were injected intraperitoneally daily for 30 d with vehicle or VCD at 40 or 80 mg/kg. Body weight, food intake, complete blood counts, and markers of liver injury and renal function were measured during VCD treatment. Complete gross necropsy and microscopic observations were performed on day 31, and ovarian follicles were counted. At 80 mg/kg, VCD destroyed primordial and primary follicles to a similar extent in both adult and peripubertal animals, although adult rats likely started with fewer follicles and therefore approached follicle depletion. Treatment with VCD did not affect body weight, but food intake was reduced in both adult and peripubertal rats treated with 80 mg/kg VCD. Adult rats treated with 80 mg/kg VCD had neutrophilia and increased BUN and creatinine; in addition, 4 of these rats were euthanized on days 25 or 26 due to peritonitis. VCD treatment did not increase alanine aminotransferase levels, a marker of liver injury, although the 80-mg/kg dose increased liver weights. In conclusion, VCD effectively destroys small preantral follicles in adult Sprague–Dawley rats, making them a suitable model of the menopausal transition of women. However, because adult rats were more sensitive to the irritant properties of VCD, the use of a lower dose should be considered. PMID:19295054

  12. Effects of 4-vinylcyclohexene diepoxide on peripubertal and adult Sprague-Dawley rats: ovarian, clinical, and pathologic outcomes.

    PubMed

    Muhammad, F Salih; Goode, Amanda K; Kock, Nancy D; Arifin, Esther A; Cline, J Mark; Adams, Michael R; Hoyer, Patricia B; Christian, Patricia J; Isom, Scott; Kaplan, Jay R; Appt, Susan E

    2009-02-01

    Young rats treated daily with intraperitoneal 4-vinylcyclohexene diepoxide (VCD) undergo selective destruction of primordial follicles, resulting in gradual ovarian failure resembling the menopausal transition in women. To determine whether VCD has similar effects on ovaries of older rats, adult and peripubertal Sprague-Dawley rats were injected intraperitoneally daily for 30 d with vehicle or VCD at 40 or 80 mg/kg. Body weight, food intake, complete blood counts, and markers of liver injury and renal function were measured during VCD treatment. Complete gross necropsy and microscopic observations were performed on day 31, and ovarian follicles were counted. At 80 mg/kg, VCD destroyed primordial and primary follicles to a similar extent in both adult and peripubertal animals, although adult rats likely started with fewer follicles and therefore approached follicle depletion. Treatment with VCD did not affect body weight, but food intake was reduced in both adult and peripubertal rats treated with 80 mg/kg VCD. Adult rats treated with 80 mg/kg VCD had neutrophilia and increased BUN and creatinine; in addition, 4 of these rats were euthanized on days 25 or 26 due to peritonitis. VCD treatment did not increase alanine aminotransferase levels, a marker of liver injury, although the 80-mg/kg dose increased liver weights. In conclusion, VCD effectively destroys small preantral follicles in adult Sprague-Dawley rats, making them a suitable model of the menopausal transition of women. However, because adult rats were more sensitive to the irritant properties of VCD, the use of a lower dose should be considered. PMID:19295054

  13. Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors.

    PubMed

    Tang, Xihe; Wang, Shuyan; Bai, Yunfei; Wu, Jianyu; Fu, Linlin; Li, Mo; Xu, Qunyuan; Xu, Zhi-Qing David; Alex Zhang, Y; Chen, Zhiguo

    2016-03-01

    Human neural stem cells (NSCs) hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB) is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs) by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs) can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine. PMID:26826927

  14. Mediation of Autophagic Cell Death by Type 3 Ryanodine Receptor (RyR3) in Adult Hippocampal Neural Stem Cells

    PubMed Central

    Chung, Kyung Min; Jeong, Eun-Ji; Park, Hyunhee; An, Hyun-Kyu; Yu, Seong-Woon

    2016-01-01

    Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+ levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs) and inositol 1,4,5-triphosphate receptors (IP3Rs), the main Ca2+ release channels located in endoplasmic reticulum (ER) membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN) cells utilizing an insulin withdrawal model of autophagic cell death (ACD). Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs—especially RyR3—were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished ACD of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+ regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology. PMID:27199668

  15. Unlike adults, children and adolescents show predominantly increased neural activation to social exclusion by members of the opposite gender.

    PubMed

    Bolling, Danielle Z; Pelphrey, Kevin A; Vander Wyk, Brent C

    2016-10-01

    The effects of group membership on brain responses to social exclusion have been investigated in adults, revealing greater anterior cingulate responses to exclusion by members of one's in-group (e.g., same-gender). However, social exclusion is a critical aspect of peer relations in youth and reaches heightened salience during adolescence, a time when social anxiety disorders are also emergent. While the behavioral and neural correlates of social exclusion in adolescence have been extensively explored, the effects of group membership on peer rejection are less clear. The current study used functional magnetic resonance imaging (fMRI) to investigate the differential neural correlates of being excluded by peers of one's same- versus opposite-gender during an online ball-toss game. Participants were a group of typically developing children and adolescents (7-17 years). As predicted, anterior cingulate cortex showed a main effect of social exclusion versus fair play. However, unlike a previous adult study, this region did not show increased activation to same-gender exclusion. Instead, several regions differentiating same- versus opposite-gender exclusion were exclusively more sensitive to exclusion by one's opposite gender. These results are discussed in the context of adolescent socio-emotional development. PMID:26592311

  16. Increased Neural Responses to Reward in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder and Their Unaffected Siblings

    PubMed Central

    von Rhein, Daniel; Cools, Roshan; Zwiers, Marcel P.; van der Schaaf, Marieke; Franke, Barbara; Luman, Marjolein; Oosterlaan, Jaap; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Hartman, Catharina A.; Faraone, Stephen V.; van Rooij, Daan; van Dongen, Eelco V.; Lojowska, Maria; Mennes, Maarten; Buitelaar, Jan

    2015-01-01

    Objective Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is unknown whether reward processing is abnormal in unaffected siblings of participants with ADHD. Method We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n=150), their unaffected siblings (n=92), and control participants (n=108), all of the same age. Results Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex, and ventral striatum during reward receipt. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and the orbitofrontal cortex during receipt. Conclusion ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters have to replicate our findings. PMID:25901776

  17. Airborne particles of the california central valley alter the lungs of healthy adult rats.

    PubMed Central

    Smith, Kevin R; Kim, Seongheon; Recendez, Julian J; Teague, Stephen V; Ménache, Margaret G; Grubbs, David E; Sioutas, Constantinos; Pinkerton, Kent E

    2003-01-01

    Epidemiologic studies have shown that airborne particulate matter (PM) with a mass median aerodynamic diameter < 10 microm (PM10) is associated with an increase in respiratory-related disease. However, there is a growing consensus that particles < 2.5 microm (PM2.5), including many in the ultrafine (< 0.1 microm) size range, may elicit greater adverse effects. PM is a complex mixture of organic and inorganic compounds; however, those components or properties responsible for biologic effects on the respiratory system have yet to be determined. During the fall and winter of 2000-2001, healthy adult Sprague-Dawley rats were exposed in six separate experiments to filtered air or combined fine (PM2.5) and ultrafine portions of ambient PM in Fresno, California, enhanced approximately 20-fold above outdoor levels. The intent of these studies was to determine if concentrated fine/ultrafine fractions of PM are cytotoxic and/or proinflammatory in the lungs of healthy adult rats. Exposures were for 4 hr/day for 3 consecutive days. The mean mass concentration of particles ranged from 190 to 847 microg/m3. PM was enriched primarily with ammonium nitrate, organic and elemental carbon, and metals. Viability of cells recovered by bronchoalveolar lavage (BAL) from rats exposed to concentrated PM was significantly decreased during 4 of 6 weeks, compared with rats exposed to filtered air (p< 0.05). Total numbers of BAL cells were increased during 1 week, and neutrophil numbers were increased during 2 weeks. These observations strongly suggest exposure to enhanced concentrations of ambient fine/ultrafine particles in Fresno is associated with mild, but significant, cellular effects in the lungs of healthy adult rats. PMID:12782490

  18. Novel Dynamics Observed in a Spiking Neural Network Model of the NTS in the Rat Hind-brain

    NASA Astrophysics Data System (ADS)

    Zhou, Jingyi; Schaffer, J. David; Dilorenzo, Patricia; Laramee, Craig

    2012-02-01

    The Nucleus of the Solitary Tract (NTS) is a hind-brain structure in the rat that is the first way-station in taste processing. Its structure and function are poorly understood. Recently our group produced a model, implemented as a spiking neural network (SNN), that successfully replicated experimental data. The model's topology was manually devised and the parameters were set by a genetic algorithm. In order to better understand its information processing capabilities, we probed the model with a variety of input spike patterns and observed a striking winner-take-all decision-making dynamic. We show how the topology and tuned parameters enable this decision to depend on precise spike timing events. It is curious that the experimental data upon which the model was originally evolved did not include winner-take-all examples; this was an emergent capability. It remains for additional experiments on rats to confirm or reject this model prediction.

  19. Axonal Elongation into Peripheral Nervous System ``Bridges'' after Central Nervous System Injury in Adult Rats

    NASA Astrophysics Data System (ADS)

    David, Samuel; Aguayo, Albert J.

    1981-11-01

    The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as ``bridges'' between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

  20. Neural correlates of the age-related changes in motor sequence learning and motor adaptation in older adults

    PubMed Central

    King, Bradley R.; Fogel, Stuart M.; Albouy, Geneviève; Doyon, Julien

    2013-01-01

    As the world's population ages, a deeper understanding of the relationship between aging and motor learning will become increasingly relevant in basic research and applied settings. In this context, this review aims to address the effects of age on motor sequence learning (MSL) and motor adaptation (MA) with respect to behavioral, neurological, and neuroimaging findings. Previous behavioral research investigating the influence of aging on motor learning has consistently reported the following results. First, the initial acquisition of motor sequences is not altered, except under conditions of increased task complexity. Second, older adults demonstrate deficits in motor sequence memory consolidation. And, third, although older adults demonstrate deficits during the exposure phase of MA paradigms, the aftereffects following removal of the sensorimotor perturbation are similar to young adults, suggesting that the adaptive ability of older adults is relatively intact. This paper will review the potential neural underpinnings of these behavioral results, with a particular emphasis on the influence of age-related dysfunctions in the cortico-striatal system on motor learning. PMID:23616757

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

    PubMed

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

    2010-07-01

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

  2. REPRODUCTIVE TOXICITY OF A SINGLE DOSE OF 1,3-DINITROBENZENE IN TWO AGES OF YOUNG ADULT MALE RATS

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-Dinitrobenzene (M-DNB). oung adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24, ...

  3. EFFECTS OF ETHANE DIMETHANESULFONATE (EDS) ON ADULT AND IMMATURE RABBIT LEYDIG CELLS: COMPARISON WITH EDS-TREATED RAT LEYDIG CELLS

    EPA Science Inventory

    Ethane-dimethanesulfonate (EDS) has been shown to selectively kill Leydig cells and depress testosterone production in adult rats. ecent study has shown that immature rat leydig cells are less sensitive to EDS exposure. here is evidence that the rabbit metabolizes EDS to methane ...

  4. Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

    EPA Science Inventory

    These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24,...

  5. Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring.

    PubMed

    Ferreira-Vieira, Talita Hélen; de Freitas-Silva, Danielle Marra; Ribeiro, Andrea Frozino; Pereira, Sílvia Rejane Castanheira; Ribeiro, Ângela Maria

    2016-03-23

    The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID:26836141

  6. Higher white adipocyte area and lower leptin production in adult rats overfed during lactation.

    PubMed

    Conceição, E P S; Trevenzoli, I H; Oliveira, E; Franco, J G; Carlos, A S; Nascimento-Saba, C C A; Moura, E G; Lisboa, P C

    2011-06-01

    Litter size reduction during lactation is a good model for childhood obesity since it induces overnutrition and programming for obesity at adulthood. Adult offspring develop higher fat mass content, hyperinsulinemia and insulin resistance, hypertension, lower HDL cholesterol, hyperphagia, and leptin resistance. Leptin resistance is often associated with hyperleptinemia. Although we observed higher SOCS3 and lower STAT3 in the hypothalamus of rats raised in small litters featuring a central leptin resistance, they showed unexpected normoleptinemia at 180 days old. Then, to clarify why early overfed rats did not develop hyperleptinemia when adult, we studied the leptin production by the visceral and subcutaneous adipose tissue and skeletal muscle as well as the morphology in the 2 different fat depots. To induce EO, litter size was reduced to 3 pups/litter (SL group) on the 3 (rd) day of life. In controls (NL group), litter size was adjusted to 10 pups/litter. Rats were killed at 180 days old. The programming of adipose tissue morphology by early overnutrition is specific between the different fat depots with hypertrophy only in the visceral compartment. In addition, the visceral adipocyte showed lower leptin content that may indicate a reduced leptin synthesis. These data suggest that adipocytes from SL rats are dysfunctional, since a higher leptin production in larger adipose cells is expected. In conclusion, postnatal nutrition is determinant for future leptin production by different fat depots as well as adipocyte morphology. These changes seem to be related to the severity of obesity and its metabolic consequences. PMID:21512961

  7. Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate.

    PubMed

    Lecca, Davide; Fumagalli, Marta; Ceruti, Stefania; Abbracchio, Maria P

    2016-08-01

    In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific 'neurogenic' areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells. Once CNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuron-to-glia communication and also control the behaviour of adult NSCs. After development, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and self-repair also via the reactivation of adult NSCs. In this respect, at least three different types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular-subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injury-activated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on how and to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377726

  8. AGE-DEPENDENT MDPV-INDUCED TASTE AVERSIONS AND THERMOREGULATION IN ADOLESCENT AND ADULT RATS

    PubMed Central

    Merluzzi, Andrew P.; Hurwitz, Zachary E.; Briscione, Maria A.; Cobuzzi, Jennifer L.; Wetzell, Bradley; Rice, Kenner C.; Riley, Anthony L.

    2013-01-01

    Adolescent rats are more sensitive to the rewarding and less sensitive to the aversive properties of various drugs of abuse than their adult counterparts. Given a nationwide increase in use of “bath salts,” the present experiment employed the conditioned taste aversion procedure to assess the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8 or 3.2 mg/kg), a common constituent in “bath salts,” in adult and adolescent rats. As similar drugs induce thermoregulatory changes in rats, temperature was recorded following MDPV administration to assess if thermoregulatory changes were related to taste aversion conditioning. Both age groups acquired taste aversions, although these aversions were weaker and developed at a slower rate in the adolescent subjects. Adolescents increased and adults decreased body temperature following MDPV administration with no correlation to aversions. The relative insensitivity of adolescents to the aversive effects of MDPV suggests that MDPV may confer an increased risk in this population. PMID:24122728

  9. A spaceflight study of synaptic plasticity in adult rat vestibular maculas

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    1994-01-01

    Behavioral signs of vestibular perturbation in altered gravity have not been well correlated with structural modifications in neurovestibular centers. This ultrastructural research investigated synaptic plasticity in hair cells of adult rat utricular maculas exposed to microgravity for nine days on a space shuttle. The hypothesis was that synaptic plasticity would be more evident in type II hair cells because they are part of a distributed modifying macular circuitry. All rats were shared with other investigators and were subjected to treatments unrelated to this experiment. Maculas were obtained from flight and control rats after shuttle return (R + 0) and nine days post-flight (R + 9). R + 9 rats had chromodacryorrhea, a sign of acute stress. Tissues were prepared for ultrastructural study by conventional methods. Ribbon synapses were counted in fifty serial sections from medial utricular macular regions of three rats of each flight and control group. Counts in fifty additional consecutive sections from one sample in each group established method reliability. All synapses were photographed and located to specific cells on mosaics of entire sections. Pooled data were analyzed statistically. Flown rats showed abnormal posture and movement at R + 0. They had statistically significant increases in total ribbon synapses and in sphere-like ribbons in both kinds of hair cells; in type II cells, pairs of synapses nearly doubled and clusters of 3 to 6 synapses increased twelve-fold. At R + 9, behavioral signs were normal. However, synapse counts remained high in both kinds of hair cells of flight maculas and were elevated in control type II cells. Only counts in type I cells showed statistically significant differences at R + 9. High synaptic counts at R + 9 may have resulted from stress due to experimental treatments. The results nevertheless demonstrate that adult maculas retain the potential for synaptic plasticity. Type II cells exhibited more synaptic plasticity, but

  10. 6-gingerol ameliorates gentamicin induced renal cortex oxidative stress and apoptosis in adult male albino rats.

    PubMed

    Hegazy, Ahmed M S; Mosaed, Mohammed M; Elshafey, Saad H; Bayomy, Naglaa A

    2016-06-01

    Ginger or Zingiber officinale which is used in traditional medicine has been found to possess antioxidant effect that can control the generation of free radicals. Free radicals are the causes of renal cell degeneration that leads to renal failure in case of gentamicin induced toxicity. This study was done to evaluate the possible protective effects of 6-gingerol as natural antioxidant on gentamicin-induced renal cortical oxidative stress and apoptosis in adult male albino rats. Forty adult male albino rats were used in this study and were randomly divided into four groups, control group; 6-gingerol treated group; gentamicin treated group and protected group (given simultaneous 6-gingerol and gentamicin). At the end of the study, blood samples were drawn for biochemical study. Kidney sections were processed for histological, and immunohistochemical examination for caspase-3 to detect apoptosis and anti heat shock protein 47 (HSP47) to detect oxidative damage. Gentamicin treated rats revealed a highly significant increase in renal function tests, tubular dilatation with marked vacuolar degeneration and desquamation of cells, interstitial hemorrhage and cellular infiltration. Immunohistochemically, gentamicin treated rats showed a strong positive immunoreaction for caspase-3 and anti heat shock protein 47 (HSP47). Protected rats showed more or less normal biochemical, histological, and immunohistochemical pictures. In conclusion, co-administration of 6-gingerol during gentamicin 'therapy' has a significant reno-protective effect in a rat model of gentamicin-induced renal damage. It is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections. PMID:27036327

  11. Neural activation in arousal and reward areas of the brain in day-active and night-active grass rats.

    PubMed

    Castillo-Ruiz, A; Nixon, J P; Smale, L; Nunez, A A

    2010-01-20

    In the diurnal unstriped Nile grass rat (Arvicanthis niloticus) access to a running wheel can trigger a shift in active phase preference, with some individuals becoming night-active (NA), while others continue to be day-active (DA). To investigate the contributions of different neural systems to the support of this shift in locomotor activity, we investigated the association between chronotype and Fos expression during the day and night in three major nuclei in the basal forebrain (BF) cholinergic (ACh) arousal system - medial septum (MS), vertical and horizontal diagonal band of Broca (VDB and HDB respectively) -, and whether neural activation in these areas was related to neural activity in the orexinergic system. We also measured Fos expression in dopaminergic and non-dopaminergic cells of two components of the reward system that also participate in arousal - the ventral tegmental area (VTA) and supramammillary nucleus (SUM). NAs and DAs were compared to animals with no wheels. NAs had elevated Fos expression at night in ACh cells, but only in the HDB. In the non-cholinergic cells of the BF of NAs, enhanced nocturnal Fos expression was almost universally seen, but only associated with activation of the orexinergic system for the MS/VDB region. For some of the areas and cell types of the BF, the patterns of Fos expression of DAs appeared similar to those of NAs, but were never associated with activation of the orexinergic system. Also common to DAs and NAs was a general increase in Fos expression in non-dopaminergic cells of the SUM and anterior VTA. Thus, in this diurnal species, voluntary exercise and a shift to a nocturnal chronotype changes neural activity in arousal and reward areas of the brain known to regulate a broad range of neural functions and behaviors, which may be also affected in human shift workers. PMID:19837140

  12. Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats.

    PubMed

    Kaplan, Kara; Echert, Ashley E; Massat, Ben; Puissant, Madeleine M; Palygin, Oleg; Geurts, Aron M; Hodges, Matthew R

    2016-05-01

    Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (∼50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4°C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5-hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID:26869713

  13. Neural responses to others' pain vary with psychopathic traits in healthy adult males.

    PubMed

    Seara-Cardoso, Ana; Viding, Essi; Lickley, Rachael A; Sebastian, Catherine L

    2015-09-01

    Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested that individuals with high levels of psychopathic traits show atypical responses to others' pain in a network of brain regions typically recruited during empathic processing (anterior insula, inferior frontal gyrus, and mid- and anterior cingulate cortex). Here, we investigated whether neural responses to others' pain vary with psychopathic traits within the general population in a similar manner to that found in individuals at the extreme end of the continuum. As predicted, variation in psychopathic traits was associated with variation in neural responses to others' pain in the network of brain regions typically engaged during empathic processing. Consistent with previous research, our findings indicated the presence of suppressor effects in the association of levels of the affective-interpersonal and lifestyle-antisocial dimensions of psychopathy with neural responses to others' pain. That is, after controlling for the influence of the other dimension, higher affective-interpersonal psychopathic traits were associated with reduced neural responses to others' pain, whilst higher lifestyle-antisocial psychopathic traits were associated with increased neural responses to others' pain. Our findings provide further evidence that atypical function in this network might represent neural markers of disrupted emotional and empathic processing; that the two dimensions of psychopathy might tap into distinct underlying vulnerabilities; and, most importantly, that the relationships observed at the extreme end of the psychopathy spectrum apply to the nonclinical distribution of these traits, providing further evidence for continuities in the mechanisms underlying psychopathic traits across the general population. PMID:25776930

  14. GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat

    PubMed Central

    Gao, Xiaoqing; Deng, Li; Wang, Yun; Yin, Ling; Yang, Chaoxian; Du, Jie; Yuan, Qionglan

    2016-01-01

    Multiple sclerosis (MS) is an autoimmune disease in the CNS. The current immunomodulating drugs for MS do not effectively prevent the progressive neurological decline. Neural stem cells (NSCs) transplantation has been proven to promote repair and functional recovery of experimental allergic encephalomyelitis (EAE) animal model for MS, and glial cell line-derived neurotrophic factor (GDNF) has also been found to have capability of promoting axonal regeneration and remyelination of regenerating axons. In the present study, to assess whether GDNF would enhance therapeutic effect of NSCs for EAE, GDNF gene-modified NSCs (GDNF/NSCs) and native NSCs were transplanted into each lateral ventricle of rats at 10 days and rats were sacrificed at 60 days after EAE immunization. We found that NSCs significantly reduced the clinical signs, and GDNF gene-modification further promoted functional recovery. GDNF/NSCs more profoundly suppressed brain inflammation and improved density of myelin compared with NSCs. The survival of GDNF/NSCs was significantly higher than that of transplanted NSCs. Transplanted GDNF/NSCs, in contrast to NSCs, differentiated into more neurons and oligodendrocytes. Moreover, the mRNA expression of oligodendrocyte lineage cells in rats with GDNF/NSCs was significantly increased compared to rats with NSCs. These results suggest that GDNF enhances therapeutic efficiency of NSCs-based therapy for EAE. PMID:27212951

  15. Properties of ionic currents from isolated adult rat carotid body chemoreceptor cells: effect of hypoxia.

    PubMed Central

    López-López, J R; González, C; Pérez-García, M T

    1997-01-01

    1. The electrical properties of chemoreceptor cells from neonatal rat and adult rabbit carotid bodies (CBs) are strikingly different. These differences have been suggested to be developmental and/or species related. To distinguish between the two possibilities, the whole-cell configuration of the patch-clamp technique was used to characterize the ionic currents present in isolated chemoreceptor cells from adult rat CBs. Since hypoxia-induced inhibition of O2-sensitive K+ currents is considered a crucial step in O2 chemoreception, the effect of hypoxia on the adult rat chemoreceptor cell currents was also studied. 2. Outward currents were carried mainly by K+, and two different components could be distinguished: a Ca(2+)-dependent K+ current (IK(Ca)) sensitive to Cd2+ and charybdotoxin (CTX), and a Ca(2+)-insensitive, voltage-dependent K+ current (IK(V)). IK(V) showed a slow voltage-dependent activation (time constant (tau) of 87.4 ms at -20 mV and 8.8 ms at +60 mV) and a very slow inactivation, described by the sum of two exponentials (tau 1 = 684 +/- 150 ms and tau 2 = 4.96 +/- 0.76 s at + 30 mV), that was almost voltage insensitive. The kinetic and pharmacological properties of IK(V) are typical of a delayed rectifier K+ channel. 3. Voltage-dependent Ca2+ currents (ICa) were present in nineteen of twenty-seven cells. TTX-sensitive Na+ currents were also observed in about 10% of the cells. 4. Low PO2 (< 10 mmHg) reduced the whole outward current amplitude by 22.17 +/- 1.96% (n = 27) at +20 mV. This effect was absent in the presence of Cd2+. Since low PO2 did not affect ICa, we conclude that hypoxia selectively blocks IK(Ca). 5. The properties of the currents recorded in adult rat chemoreceptor cells, including the specific inhibition of IK(Ca) by hypoxia, are similar to those reported in neonatal rat CB cells, implying that the differences between rat and rabbit chemoreceptor cells are species related. PMID:9080372

  16. Sympathectomy alters bone architecture in adult growing rats.

    PubMed

    Pagani, F; Sibilia, V; Cavani, F; Ferretti, M; Bertoni, L; Palumbo, C; Lattuada, N; De Luca, E; Rubinacci, A; Guidobono, F

    2008-08-15

    Sympathetic nervous system (SNS) fibres and alpha- and beta-receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine-induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone. PMID:18449939

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

    PubMed

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

    2015-11-01

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

  18. Early deprivation reduced anxiety and enhanced memory in adult male rats.

    PubMed

    Zhang, Xuliang; Wang, Bo; Jin, Jing; An, Shuming; Zeng, Qingwen; Duan, Yanhong; Yang, Liguo; Ma, Jing; Cao, Xiaohua

    2014-09-01

    The effects of early deprivation (ED, which involves both dam and littermate deprivation) on anxiety and memory are less investigated in comparison with maternal separation (MS), and it is not yet clear how ED affects long-term potentiation (LTP) in the hippocampal Schaffer collateral pathway. By using a series of behavioral tests, enzyme-linked immunosorbent assay and field potential recording, we explored the effect of pre-weaning daily 3-h ED on anxiety, memory and potential mechanisms in adult male rats. Compared with control, ED rats spent longer time in open arms of elevated plus maze and in light compartment of light-dark transition box. Consistently, stress-induced blood plasma corticosterone level was also lower in ED rats. Moreover, ED rats showed better performance in social recognition and Morris water maze test. In accordance with results in memory tests, the threshold of LTP induction in hippocampal CA3-CA1 pathway of ED rats was also reduced. Our results indicate ED reduced anxiety, but enhanced social recognition and spatial reference memory. We suggest the diminished hypothalamic-pituitary-adrenal axis response and facilitated hippocampal LTP may contribute to the anxiety-reducing and memory-enhancing effects of ED, respectively. PMID:25157962

  19. Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

    PubMed

    Asker, M E; Hassan, W A; El-Kashlan, A M

    2015-08-01

    The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 μg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress. PMID:25220112

  20. Effect of restraint and copper deficiency on blood pressure and mortality of adult rats

    SciTech Connect

    Klevay, L.M.; Halas, E.S. )

    1989-02-01

    The etiology of most hypertension is unknown; stress is thought to elevate blood pressure. Male, weanling Sprague-Dawley rats were fed a purified diet plus a drinking solution containing 10{mu}g Zn and 2{mu}g Cu/ml (acetate sulfate, respectively). Systolic blood pressure was measured without anesthesia. After being matched by mean weight (280g) and blood pressure into 4 groups of 15, groups 1 and 2 received a drinking solution without copper. After 24 days rats in groups 2 and 4 were restrained for 45 min. daily (A.M.) for 23 days in a small plastic cage (19{times}6{times}6 cm). Final pressures were affected both by stress and dietary Cu: group 1, 119; group 2, 131; group 3, 114; group 4, 123 mm Hg. One rat in each of groups 1, 3, 4 and 10 rats in group 2, died. Among these latter hemorrhage was prominent, blood being found in bladder (2), gut (2), peritoneum (2) and scrotum (1). Copper deficiency decreased cooper in both adrenal gland and liver by 58% and in heart by 29% restraint was without effect. Cardiac sodium was increased 6% only by deficiency. Results confirm the hypertensive effect of copper deficiency in adult rats and reveal that the stress of restraint increases blood pressure. Copper deficiency plus stress is harmful.

  1. Differential expression of TRPM7 in rat hepatoma and embryonic and adult hepatocytes.

    PubMed

    Lam, D Hung; Grant, Caroline E; Hill, Ceredwyn E

    2012-04-01

    TRPM7 channels are implicated in cellular survival, proliferation, and differentiation. However, a profile of TRPM7 activity in a specific cell type has not been determined from embryonic to terminally differentiated state. Here, we characterized TRPM7 expression in a spectrum of rat liver cells at different developmental stages. Using the whole-cell patch clamp technique, TRPM7-like Na(+) currents were identified in RLC-18 cells, a differentiated, proliferating hepatocellular line derived from day 17 embryonic rat liver. Currents were outwardly rectifying, enhanced in divalent-free solutions, and inhibited by intracellular Mg(2+). Reverse transcription - polymerase chain reaction (RT-PCR) revealed that RLC-18 cells express both TRPM6 and TRPM7. However, mean currents were reduced almost 80% by 1 mmol/L 2-aminoethoxyphenylborate (2-APB) and were abolished in RLC-18 cells heterologously expressing a dominant negative TRPM7 construct, suggesting that TRPM7 is the major current carrier in these cells. Functional comparison showed that relative to terminally differentiated adult rat hepatocytes, currents were 1.8 and 3.9 times higher in, respectively, RLC-18 and WIF-B cells, a rat hepatoma - human fibroblast cross. Our results demonstrate that plasma membrane TRPM7 channels are more highly expressed in proliferating cells as compared with terminally differentiated and nondividing rat hepatocytes and suggest that downregulation of this channel is associated with hepatocellular differentiation. PMID:22429021

  2. Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

    PubMed

    Klein, R M; Clancy, J; Stuart, S

    1982-11-01

    The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate. PMID:7172201

  3. Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats

    PubMed Central

    Lotan, Dafna; Benhar, Itai; Alvarez, Kathy; Mascaro-Blanco, Adita; Brimberg, Lior; Frenkel, Dan; Cunningham, Madeleine W.; Joel, Daphna

    2014-01-01

    Group A β-hemolytic streptococcal (GAS) infection is associated with a spectrum of neuropsychiatric disorders. The leading hypothesis regarding this association proposes that a GAS infection induces the production of auto-antibodies, which cross-react with neuronal determinants in the brain through the process of molecular mimicry. We have recently shown that exposure of rats to GAS antigen leads to the production of anti-neuronal antibodies concomitant with the development of behavioral alterations. The present study tested the causal role of the antibodies by assessing the behavior of naïve rats following passive transfer of purified antibodies from GAS-exposed rats. Immunoglobulin G (IgG) purified from the sera of GAS-exposed rats was infused directly into the striatum of naïve rats over a 21-day period. Their behavior in the induced-grooming, marble burying, food manipulation and beam walking assays was compared to that of naïve rats infused with IgG purified from adjuvant-exposed rats as well as of naïve rats. The pattern of in vivo antibody deposition in rat brain was evaluated using immunofluorescence and colocalization. Infusion of IgG from GAS-exposed rats to naïve rats led to behavioral and motor alterations partially mimicking those seen in GAS-exposed rats. IgG from GAS-exposed rats reacted with D1 and D2 dopamine receptors and 5HT-2A and 5HT-2C serotonin receptors in vitro. In vivo, IgG deposits in the striatum of infused rats colocalized with specific brain proteins such as dopamine receptors, the serotonin transporter and other neuronal proteins. Our results demonstrate the potential pathogenic role of autoantibodies produced following exposure to GAS in the induction of behavioral and motor alterations, and support a causal role for autoantibodies in GAS-related neuropsychiatric disorders. PMID:24561489

  4. Early-life stress induces anxiety-like behaviors and activity imbalances in the medial prefrontal cortex and amygdala in adult rats.

    PubMed

    Ishikawa, Junko; Nishimura, Ryoichi; Ishikawa, Akinori

    2015-02-01

    Early-life stress increases the prevalence of psychiatric diseases associated with emotional dysregulation. Emotional regulation requires the inhibitory influence of the medial prefrontal cortex (mPFC) on amygdalar activity, and dysfunction of this system is believed to induce anxiety. Because mPFC and amygdala have dense reciprocal connections and projections between them continue to develop until adolescence, early-life stress may impair the function of this circuit and cause emotional dysregulation. We examined the effects of stress during circuit development on anxiety-like behaviors, neural activities in the mPFC and amygdala, and impulse transmission in the mPFC-amygdala circuit in adult rats. Early-life stress, unpredictable stress twice a day for 12 days following early weaning, increased anxiety-like behaviors in the open-field and elevated plus-maze tests. In the open-field test, stress altered Fos expression in the mPFC and amygdala. Compared to non-stressed rats, which were exposed to neither unpredictable stress nor early weaning, stressed rats exhibited decreased Fos expression in the right superficial layers of the infralimbic cortex and increased Fos expression in the right basolateral amygdala and both sides of the central amygdala. Electrophysiological analysis revealed that excitatory latencies of mPFC neurons to amygdalar stimulation in stressed rats were significantly longer than control rats in the right, but not left, hemisphere. Stress had no effect on excitatory latencies of amygdalar neurons to mPFC stimulation in the mPFC-amygdala circuits in the both hemisphere. These data suggest that early-life stress impairs the mPFC-amygdala circuit development, resulting in imbalanced mPFC and amygdala activities and anxiety-like behaviors. PMID:25581710

  5. Differential Effects of Inhaled Toluene on Locomotor Activity in Adolescent and Adult Rats

    PubMed Central

    Batis, Jeffery C.; Hannigan, John H.; Bowen, Scott E.

    2010-01-01

    Inhalant abuse is a world-wide public health concern among adolescents. Most preclinical studies have assessed inhalant effects in adult animals leaving unclear how behavioral effects differ in younger animals. We exposed adolescent (postnatal day [PN] 28) and adult (PN90) male rats to toluene using 1 of 3 exposure patterns. These patterns modeled those reported in toluene abuse in teens and varied concentration, number and length of exposures, as well as the inter-exposure interval. Animals were exposed repeatedly over 12 days to toluene concentrations of 0, 8,000 or 16,000 parts per million (ppm). Locomotor activity was quantified during toluene exposures and for 30 min following completion of the final daily toluene exposure. For each exposure pattern, there were significant toluene concentration-related increases and decreases in locomotor activity compared to the 0-ppm “air” controls at both ages. These changes depended upon when activity was measured – during or following exposure. Compared to adults, adolescents displayed greater locomotor activity on the first day and generally greater increases in activity over days than adults during toluene exposure. Adults displayed g