Neuroscience
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Comparative Study
Age-related changes in brain-derived neurotrophic factor and tyrosine kinase receptor isoforms in the hippocampus and hypothalamus in male rats.
A large amount of aging individuals show diminished cognitive and endocrine capabilities. The main brain areas involved in these changes are the hippocampus and hypothalamus, two regions possessing high plasticity and implicated in cognitive and endocrine functions, respectively. Among neurotrophins (considered as genuine molecular mediators of synaptic plasticity), brain-derived neurotrophic factor (BDNF) exhibits in adult rats, the highest concentrations in the hippocampus and hypothalamus. ⋯ FL has a neuronal localization also gradually decreased in the hippocampus and in the hypothalamus throughout lifespan. These reductions were significant at 21 and 30 days old, respectively. All the changes reported here could contribute to the reduced plasticity of these regions observed in old rats.
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The subcellular distributions and co-associations of the gap junction-forming proteins connexin 47 and connexin 32 were investigated in oligodendrocytes of adult mouse and rat CNS. By confocal immunofluorescence light microscopy, abundant connexin 47 was co-localized with astrocytic connexin 43 on oligodendrocyte somata, and along myelinated fibers, whereas connexin 32 without connexin 47 was co-localized with contactin-associated protein (caspr) in paranodes. By thin-section transmission electron microscopy, connexin 47 immunolabeling was on the oligodendrocyte side of gap junctions between oligodendrocyte somata and astrocytes. ⋯ These results clarify the locations and connexin compositions of heterologous and autologous oligodendrocyte gap junctions, identify autologous gap junctions at paranodes as potential sites for modulating paranodal electrical properties, and reveal connexin 47-containing and connexin 32-containing gap junctions as conduits for long-distance intracellular and intercellular movement of ions and associated osmotic water. The autologous gap junctions may regulate paranodal electrical properties during saltatory conduction. Acting in series and in parallel, autologous and heterologous oligodendrocyte gap junctions provide essential pathways for intra- and intercellular ionic homeostasis.
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Comparative Study
Spinal phospholipase A2 in inflammatory hyperalgesia: role of the small, secretory phospholipase A2.
Current work emphasizes that peripheral tissue injury and inflammation results in a heightened sensitivity to subsequent noxious input (hyperalgesia) that is mediated in large part by the spinal synthesis and release of eicosanoids, in particular prostaglandins. Secreted phospholipase A(2)s (sPLA(2)s) form a class of structurally related enzymes that release arachidonic acid from cell membranes that is further processed to produce eicosanoids. We hypothesized that spinal sPLA(2)s may contribute to inflammation-induced hyperalgesia. ⋯ IT LY311727 also suppressed thermal hyperalgesia induced by IT injection of substance P (30 nmol). Using in vivo spinal microdialysis, we found that IT injection of LY311727 attenuated prostaglandin E(2) release into spinal dialysate otherwise evoked by the IT injection of substance P. Taken together, this work points to a role for constitutive sPLA(2)s in spinal nociceptive processing.
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Nitric oxide (NO) is a neurotransmitter of the autonomic nerves in the urogenital tract, in particular the release of NO in the cavernous tissue is of importance for maintaining erection. However, the regulation of NO formation in neurons of the corpus cavernosum is poorly understood. Here, we report, that upon electrical stimulation of isolated rabbit corpus cavernosum, NO/NO(2-) was formed and released in a reproducible fashion. ⋯ The effect of the phosphodiesterase inhibitor zaprinast (10(-4) M), was not significant (209+/-53%, n.s). In contrast, inhibition of sGC by 1-H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (10(-5) M) decreased the release of NO/NO(2-) to 64+/-14% (P<0.05). Our results suggest that NO/NO(2-) is released by nitrergic neurons within the rabbit corpus cavernosum and that the release is subject to modulation by the sGC/cGMP pathway, but not to modulation by acetylcholine or noradrenaline.
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We used the hot plate test and the formalin test to evaluate the antinociception of choline after i.c.v. or i.v. administration. The analgesic mechanism of choline was also studied. The response latency of mice was significantly prolonged in the hot plate test after choline (90-120 mug/animals) i.c.v. administration in a dose-dependent manner. ⋯ Similarly, coadministration of choline (2 mg/kg) with morphine (0.165 mg/kg) significantly increased the antinociception of morphine in the late phase, but had no effect in the early phase. These results demonstrate that activation of alpha7 nicotinic receptors by choline elicits antinociceptive effects both in an acute thermal pain model and in an inflammatory pain model. Choline holds promise for development as a non-addictive analgesic drug and in reducing the regular dose of aspirin or morphine in inflammatory pain.