Neuroscience
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In the rodent, arcuate nucleus of the hypothalamus (ARH)-derived neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons have efferent projections throughout the hypothalamus that do not fully mature until the second and third postnatal weeks. Since this process is likely completed by birth in primates we characterized the ontogeny of NPY and melanocortin systems in the fetal Japanese macaque during the late second (G100), early third (G130) and late third trimesters (G170). NPY mRNA was expressed in the ARH, paraventricular nucleus (PVH), and dorsomedial nucleus of the hypothalamus (DMH) as early as G100. ⋯ In addition, cocaine and amphetamine-related transcript (CART) and alpha-melanocyte stimulating hormone (alphaMSH) were not colocalized in fibers or cell bodies. As a consequence of the prenatal development of these neuropeptide systems in the NHP, the maternal environment may critically influence these circuits. Additionally, because differences exist in the neuroanatomy of NPY and melanocortin circuitry the regulation of these systems may be different in primates than in rodents.
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In the present study we combined FM 1-43 imaging and electrophysiological recording of miniature end-plate currents (MEPCs) to determine the role of extracellular calcium in synaptic vesicle exo- and endocytosis at the frog motor nerve terminals. We replaced extracellular Ca2+ ions with other bivalent cations (Sr2+, Ba2+, Cd2+, Mg2+) or used a calcium-free solution and monitored fluorescent staining of the nerve terminals in the presence of caffeine, which promotes the release of Ca2+ from intracellular stores. Caffeine has induced FM1-43 internalization only in the presence of bivalent cations in the external solution. ⋯ This effect of a calcium-free solution was not due to a decrease in exocytosis, because caffeine-induced FM1-43 unloading from the previously loaded nerve terminals, as well as a degree of the MEPCs frequency increase, was unchanged. We conclude that the presence of Ca2+ or other bivalent cations in extracellular space is necessary for endocytosis but not for exocytosis of synaptic vesicles, while transmitter release is promoted by efflux of Ca2+ from intracellular stores. The effect of extracellular Ca2+ on endocytosis might be driven by the non-specific interactions with membrane lipids.
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Men are typically reported to have higher pain thresholds than women. Gonadal hormones, particularly testosterone for males, may contribute to this effect. This study tested whether changes in the male hormonal milieu early or late in development alter the inflammatory pain induced by carrageenan (CARR, 3%, intraarticular). ⋯ Both doses of morphine increased mechanical and thermal thresholds. However, compared with the control group, 1 mg/kg morphine was equally effective in reducing mechanical hyperalgesia among groups of animals gonadectomized as adults, but less effective in males gonadectomized neonatally. The results suggest that in males: 1. the antihyperalgesic effect of testosterone (or its metabolites) in CARR-induced inflammation is established during development and maintained by circulating levels of testosterone in adulthood; 2. the nociception-related interaction between the opioid and gonadal systems influences the sensitivity to mechanical stimuli and is likely established during the period of sexual differentiation.
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We investigated the contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus (VSP) following acute masseter muscle injury in male rats with or without temporomandibular joint (TMJ) inflammation persisting for 7 days. TMJ inflammation was evoked by an injection of complete Freund's adjuvant (CFA). Two hours after formalin injection into the masseter muscle produced Fos-like immunoreactivity (Fos-LI) in several regions of the VSP and upper cervical spinal cord (C2), such as ventrolateral (vl) area of the trigeminal subnucleus caudalis (Vc)/subnucleus interpolaris (Vi) transition (vl-Vi/Vc), paratrigeminal nucleus (dPa5), middle portion of the Vc (mid-Vc) and Vc/C2 transition (Vc/C2) regions in both groups. ⋯ The Fos-LI response was not affected by i.v. administration of ketanserin (0.01, 0.1 mg/rat) or tropisetron (0.01 mg/rat). In non-CFA group, these antagonists given locally did not reduce the Fos-LI response. These results suggest that peripheral 5-HT2A and 5-HT3 receptors contribute to nociceptive processing in the masseter muscle in TMJ inflammatory conditions.
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In the CNS, l-serine (l-Ser) plays an essential role in neuronal survival by evoking a variety of biological responses in glial cells. Initially, we examined whether glutamate, hydrogen peroxide (H(2)O(2)), interleukin-1 (IL-1) beta, and sodium nitroprusside (SNP) induce the secretion of l-Ser in astrocytes isolated from Wistar Kyoto rats (WKY). The secretion of l-Ser was significantly induced with glutamate and SNP in cultured astrocytes. ⋯ The results suggest that the attenuated secretion of l-Ser in astrocytes is involved in neuronal vulnerability and survival in SHRSP during the production of glutamate, as the secretion of l-Ser, which is stimulated by glutamate, is closely related to the protective effect against glutamate-mediated neurotoxicity. We conclude that glutamate and SNP up-regulate the secretion of l-Ser in primary astrocytes. Secretion of l-Ser is regulated in astrocytes in response to glutamate and nitric oxide and may correspond to the level of l-Ser needed for neuronal survival during brain insults such as ischemic stroke in SHRSP.