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Developing Rat Brain (developing + rat_brain)
Selected AbstractsFas/CD95/APO-1 Can Function as a Death Receptor for Neuronal Cells in Vitro and in Vivo and is Upregulated Following Cerebral Hypoxic-Ischemic Injury to the Developing Rat BrainBRAIN PATHOLOGY, Issue 1 2000Ursula Felderhoff-Mueser Fas/CD95/Apo-1 is a cell surface receptor that transduces apoptotic death signals following activation and has been implicated in triggering apoptosis in infected or damaged cells in disease states. Apoptosis is a major mechanism of neuronal loss following hypoxic-ischemic injury to the developing brain, although the role of Fas in this process has not been studied in detail. In the present study, we have investigated the expression and function of Fas in neuronal cells in vitro and in vivo. Fas was found to be expressed in the 14 day old rat brain, with strongest expression in the cortex, hippocampus and cerebellum. Cross-linking of Fas induced neuronal apoptosis both in neuronal PC12 cells in culture and following intracerebral injection in vivo, indicating that neuronal Fas was functional as a death receptor. This death was shown to be caspase dependent in primary neuronal cultures and was blocked by the selective caspase 8 inhibitor IETD. Finally, cerebral hypoxia-ischemia resulted in a strong lateralised upregulation of Fas in the hippocampus, that peaked six to twelve hours after the insult and was greater on the side of injury. These results suggest that Fas may be involved in neuronal apoptosis following hypoxic-ischemic injury to the developing brain. [source] A Genomic Analysis of Subclinical Hypothyroidism in Hippocampus and Neocortex of the Developing rat BrainJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2009J. E. Royland No abstract is available for this article. [source] Isolation and expression of a novel mitochondrial septin that interacts with CRMP/CRAM in the developing neuronesGENES TO CELLS, Issue 2 2003Shusuke Takahashi Background: Collapsin response mediator proteins (CRMPs) and CRAM belong to the unc-33 gene family which is implicated in axon guidance and outgrowth during neural development. However, their exact roles remain largely unknown. To understand the molecular basis of CRMP/CRAM function, we have undertaken to identify CRMP/CRAM interacting proteins. Results: We have identified a novel mitochondrial septin (M-septin) as one of the CRMP/CRAM interacting proteins from the developing rat brain. M-septin is a major, alternatively spliced variant of the H5 gene in developing mouse brain and its expression is up-regulated during the neuronal differentiation of embryonal carcinoma P19 cells. In COS-7 cells, M-septin is specifically localized to mitochondria whereas H5 is diffusely distributed to the perinuclear cytoplasm and plasma membranes. In contrast to H5, M-septin induces the mitochondrial translocation of CRAM but not CRMP2. Finally, M-Septin is found to be transiently translocated to mitochondria before the induction of the neurites and then dissociates from the mitochondria after neurite extension in P19 cells. Conclusions: Our results suggest that M-septin has a role which is distinct from H5, and together with CRMP/CRAM, may play an important role in the neuronal differentiation and axon guidance through the control of mitochondrial function. [source] Transient expression of endothelins in the amoeboid microglial cells in the developing rat brainGLIA, Issue 6 2006Chun-Yun Wu Abstract Amoeboid microglial cells (AMC) which transiently exist in the corpus callosum in the postnatal rat brain expressed endothelins (ETs), specifically endothelin-1 (ET-1) and ET3 as revealed by real time RT-PCR. ET immunoreactive AMC occurred in large numbers at birth, but were progressively reduced with age and were undetected in 14 days. In rats subjected to hypoxia exposure, ET immunoexpression in AMC was reduced but the incidence of apoptotic cells was not increased when compared with the control suggesting that this was due to its downregulation that may help regulate the constriction of blood vessels bearing ET-A receptor. AMC were endowed ET-B receptor indicating that ET released by the cells may also act via an autocrine manner. In microglia activated by lipopolysaccharide (LPS), ET-1 mNA expression coupled with that of monocyte chemoattractant protein (MCP-1) and stromal derived factor-1 (SDF-1) was markedly increased; ET-3 mRNA, however, remained unaffected. AMC exposed to oxygen glucose deprivation (OGD) in vitro resulted in increase in both ET-1 and ET-3 mRNA expression. It is suggested that the downregulated ETs expression in vivo of AMC subjected to hypoxia as opposed to its upregulated expression in vitro may be due to the complexity of the brain tissue. Furthermore, the differential ET-1 and ET-3 mRNA expression in LPS and OGD treatments may be due to different signaling pathways independently regulating the two isoforms. The present novel finding has added microglia as a new cellular source of ET that may take part in multiple functions including regulating vascular constriction and chemokines release. © 2006 Wiley-Liss, Inc. [source] Translationally distinct populations of NMDA receptor subunit NR1 mRNA in the developing rat brainJOURNAL OF NEUROCHEMISTRY, Issue 5 2003Marc Awobuluyi Abstract The translational activity of the NMDA subunit 1 (NR1) mRNA was examined in the developing rat brain by sucrose gradient fractionation. One translationally-active pool of NR1 mRNA was associated with large polyribosomes (polysomes) over the entire developmental period examined. A second NR1 mRNA pool, approximately half of the NR1 mRNA at post-natal day 4, sedimented only within the two to three ribosome range, indicating that it was translationally blocked during early brain development despite active translation of mRNAs coding for the NR2 subunits of the receptor. At post-natal day 4, both NR1 mRNA pools were distributed throughout the brain and contained similar profiles of NR1 mRNA splice variants, except that NR1-3 appeared to be present only in the translationally-blocked NR1 pool. After post-natal day 8, the translationally-blocked NR1 mRNA pool became progressively active within a background of globally-decreasing brain translational activity. [source] Potential of umbilical cord blood cells for brain repairJOURNAL OF NEUROCHEMISTRY, Issue 2002P. R. Sanberg Our laboratory is characterizing the mononuclear cells from human umbilical cord blood (HUCB) for possible therapeutic value. Studies on HUCB cells demonstrated their ability to respond to growth factors by increased expression of neural markers and down regulation of several genes associated with development of blood lines. HUCB cells were also transplanted into the subventricular zone of the developing rat brain. It was found that some of the HUCB cells responded to external factors and were able to adopt neural fates similar to endogenous stem cells. We also tested whether intravenously infused HUCB cells enter brain, survive, differentiate and improve neurological functional recovery after stroke or traumatic brain injury (TBI) in rats. HUCB cells were injected into the tail vein at least 24 h after stroke or TBI. Behavioral impairments were significantly improved as early as 14 days in both TBI and stroke animals, compared to controls. Injected cells entered brain and migrated into the parenchyma of the injured brain. Some of these expressed neuronal, astrocytic, or endothelial markers. Our data suggest that intravenous administration of HUCB cells can provide neural stem cells, and may be a useful treatment for brain repair. Acknowledgements:, Supported by Saneron CCEL Therapeutics, Inc. and a FL Hi-Tech Corridor Grant. [source] AUF1 and Hu proteins in the developing rat brain: Implication in the proliferation and differentiation of neural progenitorsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2009Dolores Hambardzumyan Abstract Posttranscriptional events such as RNA stabilization are important for cell differentiation, but little is known about the impact of AU-rich binding proteins (AUBPs) on the fate of neural cells. Expression of destabilizing AUBPs such as AUF1 and neuronal-specific stabilizing proteins such as HuB, HuC and HuD was therefore analyzed in the developing central nervous system. Real-time RT-PCR indicated a specific developmental pattern in the postnatal cerebellum, with a progressive down-regulation of AUF1 from P1, whereas HuB was strongly up-regulated at about P7. These changes were accompanied by a progressive increase in AUF1p45 and the disappearance of one HuB isoform from P15, suggesting particular roles for these AUBPs in the developing cerebellum. AUF1 was detected in the three main cerebellar layers, whereas Hu proteins were found only in postmitotic neurons. A role for Hu proteins in the early stages of neuronal differentiation is further supported by arrest of cell proliferation following induction of HuB or HuD expression in a neural stem cell line. The decrease in nestin expression suggest that HuD, but not HuB, favors the transition of neural progenitors into early neuroblasts, but other factors are most probably required for their full differentiation into neurons, insofar as GAP-43 was not detected in HuD-transfected cells. These data suggest critical roles for HuB at the very earliest stages of neuronal differentiation, such as cell cycle exit, and HuD might also be involved in the transition of neural progenitors into early neuroblasts. Taken together, the present results strengthen the importance of AUBPs in brain ontogenesis. © 2008 Wiley-Liss, Inc. [source] Dock4 regulates dendritic development in hippocampal neuronsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2008Shuhei Ueda Abstract Dendrite development is required for establishing proper neuronal connectivity. Rho-family small GTPases have been reported to play important roles in the regulation of dendritic growth and morphology. However, the molecular mechanisms that control the activities of Rho GTPases in developing dendrites are not well understood. In the present study we found Dock4, an activator of the small GTPase Rac, to have a role in regulating dendritic growth and branching in rat hippocampal neurons. Dock4 is highly expressed in the developing rat brain, predominantly in hippocampal neurons. In dissociated cultured hippocampal neurons, the expression of Dock4 protein is up-regulated after between 3 and 8 days in culture, when dendrites begin to grow. Knockdown of endogenous Dock4 results in reduced dendritic growth and branching. Conversely, overexpression of Dock4 with its binding partner ELMO2 enhances the numbers of dendrites and dendritic branches. These morphological effects elicited by Dock4 and ELMO2 require Rac activation and the C-terminal Crk-binding region of Dock4. Indeed, Dock4 forms a complex with ELMO2 and CrkII in hippocampal neurons. These findings demonstrate a new function of the Rac activator Dock4 in dendritic morphogenesis in hippocampal neurons. © 2008 Wiley-Liss, Inc. [source] Characterization of thromboxane A2 receptor signaling in developing rat oligodendrocytes: Nuclear receptor localization and stimulation of myelin basic protein expressionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2006Santosh Ramamurthy Abstract The present work investigates the role of thromboxane A2 (TXA2) receptors in the development of oligodendrocytes (OLGs). The results demonstrate that the proteins of the TXA2 signaling pathway, i.e., cyclooxygenase (COX-1), TXA2 synthase (TS), and TXA2 receptor (TPR) are expressed in the developing rat brain during myelination. Furthermore, culture of OLG progenitor cells (OPCs) revealed that the expression levels of these proteins as well as TXA2 synthesis increase during OLG maturation. Separate studies established that activation of TPRs by the agonist U46619 increases intracellular calcium in both OPCs and OLGs as visualized by digital fluorescence imaging. Immunocytochemical staining demonstrated that TPRs are localized in the plasma membrane and perinuclear compartments in OPCs. However, during OLG differentiation, TPRs shift their localization pattern and also become associated with the nuclear compartment. This shift to nuclear localization was confirmed by biochemical analysis in cultured cells and by immunocytochemical analysis in developing rat brain. Finally, it was found that U46619 activation of TPRs in maturing OLGs resulted in enhanced myelin basic protein (MBP) expression. Alternatively, inhibition of endogenous TPR signaling led to reduced MBP expression. Furthermore, TPR-mediated MBP expression was found to be associated with increased transcription from the MBP promoter using a MBP-luciferase reporter. Collectively, these findings suggest a novel TPR signaling pathway in OLGs and a potential role for this signaling during OLG maturation and myelin production. © 2006 Wiley-Liss, Inc. [source] Thyroid hormone stimulates ,-glutamyl transpeptidase in the developing rat cerebra and in astroglial culturesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Asmita Dasgupta Abstract Hypothyroidism in the developing rat brain is associated with enhanced oxidative stress, one of the earliest manifestations of which is a decline in the level of glutathione (GSH). To investigate the role of thyroid hormone (TH) on GSH homeostasis, the effect of TH on ,-glutamyl transpeptidase (,GT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral ,GT at all postnatal ages examined (postnatal day 1,20) with a maximum inhibition of 42% at postnatal day 10. Intraperitoneal injection of TH to 15-day-old rat pups increased the specific activity of ,GT by 25-30% within 4,6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of ,GT by 30,40% within 4,6 hr. The induction of ,GT by TH was blocked by actinomycin D or cycloheximide. ,GT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the ,GT-inhibitor, acivicin, GSH released in the culture medium of astrocytes increased linearly for at least 6 hr and TH had no effect on this accumulation pattern. In the absence of acivicin, GSH content of the medium from TH-treated cells was significantly lower than that of untreated controls due to activation of ,GT by TH and a faster processing of GSH. Because the products of ,GT reaction are putative precursors for neuronal GSH, the activation of ,GT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||