Journal of neuroscience research
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Acetylcholine (ACh) is synthesized by choline acetyltransferase (ChAT) in the cytoplasm of cholinergic nerve terminals and transported into synaptic vesicles by vesicular ACh transporter (VAChT). The genes encoding ChAT and VAChT are colocalized within the genome, and their products are known to be coregulated by various neurotrophic factors. In the present study, nerve growth factor (NGF; 100 ng/ml) was shown to enhance expression of VAChT and ChAT mRNA in primary cultured rat embryonic septal cells. ⋯ In contrast, the numbers of immunocytochemically positive cells were unaffected. Thus, NGF appears to augment ACh synthesis, its transport into synaptic vesicles, and its subsequent release. The data also suggest that NGF facilitates growth and development of cholinergic neurons, but not their survival.
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The expression of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B are both increased after global ischemia. Therefore, a protective action of BDNF against the delayed degeneration of vulnerable neurons has been suggested. We have investigated the neuroprotective action of BDNF in global ischemia induced by a four-vessel occlusion in the rat. ⋯ Additionally, astroglial activation and macrophage infiltration, which were observed in association with neuronal death, were inhibited by BDNF. This was paralleled by an inhibition of inducible nitric oxide synthase (iNOS) expression in the hippocampus. Thus, the observed neuroprotective effects of continuous BDNF administration after reperfusion suggest a therapeutic potential for BDNF in cerebral ischemia.
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Delayed Wallerian degeneration after neuronal injury is a feature of the C57BL/Wld(s) mouse mutant. In the present study, we examined the effect of unilateral controlled cortical impact (CCI) on motor and cognitive performance in C57BL/6 and C57BL/Wld(s) mice. Performance on a beam-walking task was impaired in both injured groups over the first 3 weeks; however, between 28 and 35 days post injury, C57BL/6 mice continued to improve whereas C57BL/Wld(s) mice showed increased footfaults. ⋯ C57BL/Wld(s) mice also demonstrated improved working memory performance as compared with C57BL/6 mice when trained on days 21-22 after injury; this effect was lost on days 23 and 24, and was not evident in other animals tested in the same task at 28-31 days following injury. These results indicate a marked delay in motor and cognitive impairment following CCI in C57BL/Wld(s) mice compared with injured C57BL/6 controls. This is consistent with previous work showing delayed temporal evolution of neuronal degeneration in C57BL/Wld(s) mice and suggests CCI may be a suitable model for examining the functional consequences of traumatic brain injury (TBI) in genetically altered mice.
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We have used an animal model of traumatic brain injury (TBI) that incorporates both the neurotransmitter toxicity of fluid percussion TBI and deafferentation of bilateral entorhinal cortical (BEC) lesion to explore whether administration of muscarinic cholinergic or N-methyl-D-aspartate glutamatergic antagonists prior to injury ameliorates cognitive morbidity. Fifteen minutes prior to moderate central fluid percussion TBI, rats were given intraperitoneal injections of either scopolamine (1.0 mg/kg) or MK-801 (0.3 mg/kg) and 24 hr later underwent BEC lesion. Body weight was followed for 5 days postinjury, as was beam balance and beam walk performance to assure motor recovery prior to spatial memory testing. ⋯ Interestingly, short-term cognitive deficits assessed on days 11-15 were differentially affected by the two drugs: MK-801 pretreatment enhanced the recovery of spatial memory performance, whereas scopolamine pretreatment did not. Long-term (days 60-64) deficits in spatial memory were not altered by pretreatment with either drug. Our results suggest that, unlike fluid percussion TBI alone, behavioral impairment may require more select intervention when deafferentation is part of the head trauma pathology.
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DA11 is the first fatty acid binding protein (FABP) for which gene expression has been shown to be upregulated following neuronal injury in the adult peripheral nervous system. To understand better the potential regulatory role(s) of this unique FABP in axonal growth and neuronal differentiation, we undertook a temporal and spatial study of DA11 gene expression in the developing rat central nervous system (CNS). Transient upregulation of DA11 mRNA and protein levels in CNS tissues were quantified by Northern blot hybridization and Western immunoblot analyses at different developmental ages. ⋯ Localization of DA11-like immunoreactivity to specific CNS tissues, cell types, and intracellular compartments at P9 revealed a spatial pattern of neuronal expression different than that reported for other FABPs. DA11 protein was detected in the nucleus, cytoplasm, axons, and dendrites of differentiating neurons in cerebral cortex, hippocampus, cerebellum, brain stem, spinal cord, and olfactory bulb. The strong association of DA11 gene expression with development throughout the CNS suggests that this unique FABP plays an important role in axonal growth and neuronal differentiation in many different neuronal populations.