Neuroscience
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The mechanisms initiating post-spinal cord injury (SCI) apoptotic cell death remain incompletely understood. The p75 neurotrophin receptor (p75(NTR)) has been shown to exert both pro-survival and pro-apoptotic effects on neural cells in vitro. While a previous study had shown that there is decreased oligodendrocyte apoptosis distal to a clean partial transection injury of the cord in mice with nonfunctional p75(NTR), most human spinal cord injuries do not involve partial transections but are rather due to compression/contusion injuries with significant perilesional ischemia. ⋯ Furthermore, the wild-type animals had dramatically improved survival and enhanced locomotor recovery at 8 weeks after SCI when compared with the p75(NTR) null mice. Also at 8 weeks, there were significantly more neurons present at the injury site of wild-type mice when compared with p75 null mice. We conclude that the p75(NTR) receptor is integral to neuronal cell survival and endogenous reparative mechanisms after compressive/contusive SCI.
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A high soy diet reduces programmed cell death and enhances bcl-xL expression in experimental stroke.
Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. We have shown that a high soy diet significantly reduces infarct size following permanent middle cerebral artery occlusion (MCAO). Here, we tested the hypothesis that a high soy diet would attenuate programmed cell death after stroke. ⋯ Immunohistochemistry revealed increased neuronal expression of bcl-2 and bcl-x(L) in the ischemic cortex of both IFP and SP rats following tMCAO. These results suggest that a high soy diet decreases both caspase-dependent and caspase-independent programmed cell death following tMCAO. Further, a high soy diet enhances expression of the cell survival factor bcl-x(L) following tMCAO, contributing to the neuroprotective effects of soy in the ischemic cortex.
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This study investigated whether somatostatin (SST) modulates the excitability of nociceptive trigeminal ganglion (TRG) neurons that innervate the nasal mucosa and project to the upper cervical (C(1)) dorsal horn by using perforated-patch clamping, retrograde-labeling, and immunohistochemistry. Fluorogold (FG) retrograde labeling was used to identify the rat TRG neurons innervating the nasal mucosa, while microbeads (MB) were used to label neurons projected onto the superficial layer of the C(1) dorsal horn. FG-labeled small-diameter TRG neurons exhibited SST(2A) receptor immunoreactivity (19%) and half of these neurons were also labeled with MB. ⋯ Under voltage-clamp conditions, SST (1 microM) significantly increased the voltage-gated K(+) transient (I(A)) and sustained (I(K)) currents and these increases were abolished by coapplication of CYN154806 (1 microM). In the presence of both 4-aminopyridine (6 mM) and tetraethylammonium (10 mM), no significant changes in the membrane potential in response to SST application were found. These results suggest that modulation of trigeminal nociceptive transmission in the C(1) dorsal horn by activation of SST(2A) receptors occurs at the level of small-diameter TRG cell bodies and/or their afferent terminals, and that this may be related to regulation of protective upper-airway reflexes.
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Dynorphins are endogenous opioid peptide products of the prodynorphin gene. An extensive literature suggests that dynorphins have deleterious effects on CNS injury outcome. We thus examined whether a deficiency of dynorphin would protect against tissue damage after spinal cord injury (SCI), and if individual cell types would be specifically affected. ⋯ Our results indicate that dynorphin peptides affect the extent of post-injury caspase-3 activation, and that glia are especially sensitive to these effects. By promoting caspase-3 activation, dynorphin peptides likely increase the probability of glial apoptosis after SCI. While normally beneficial, our findings suggest that prodynorphin or its peptide products become maladaptive following SCI and contribute to secondary injury.
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Hippocampal granule cells (GCs) are continuously generated in the subgranular zone of the dentate gyrus (DG) and functionally incorporated to dentate neural circuits even in adulthood. This raises a question about the fate of neonatally born GCs in adult DG. Do they exist until adulthood or are they largely superseded by adult-born GCs? To investigate this question, we examined the contributions of postnatally born GCs to the adult mouse DG. ⋯ We defined BrdU- and Prox1-double positive cells as newborn GCs and analyzed their density and distribution in the granule cell layer (gcl), revealing that newborn GCs of each group still existed 6 months after BrdU injections and that the density of GCs born during P0-2 (group 1) was significantly higher compared with the other groups. Although the density of newborn GCs in the each group did not differ between male and female, the radial distribution of them in gcl showed some differences, that is, male newborn GCs localized toward the molecular layer compared with female ones in group 1, while to the hilus in group 2. These results suggest that GCs born in early postnatal days numerically dominate adult DG and that there exist sex differences in GC localizations which depend on the time when they were born.