Neuroscience
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Ionotropic glutamate receptors are ligand-gated ion channels that help mediate rapid excitatory neurotransmission in the CNS. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are critical for synaptic plasticity in central nociceptive transmission. The current study was designed to investigate the role of the AMPA receptor subunit, GluR1, and its phosphorylated forms (at Ser-831 and Ser-845) in central sensitization in rat spinal cord. Western blots and immunohistochemistry were performed to examine the expression and localization of GluR1 and the phosphorylated forms of GluR1 (phospho-GluR1) at Ser-831 and Ser-845 with specific antibodies. ⋯ A significant upregulation of phospho-GluR1 both at Ser-831 and Ser-845 was found by 5 min after capsaicin treatment, and this increase lasted at least 60 min. Immunostaining showed that GluR1 and its phosphorylated forms were localized in the superficial laminae of dorsal horn and quantitative image analysis supported the immunoblotting results. Our findings are consistent with the suggestions that AMPA receptors show increased responsiveness because of their phosphorylation and that this may contribute to central sensitization following intradermal injection of capsaicin.
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In the present study, the expression of the HuC/D RNA-binding proteins, a marker of neurons that have left the mitotic cycle, in cells migrating from the olfactory neuroepithelium toward the telencephalon in the chick embryo was investigated by means of immunofluorescence and confocal laser microscopy. Results showed that this migratory cell population is early and massively labeled by the a-HuC/D antibody starting from the first olfactory pit stage. At this developmental stage, olfactory migratory cells appeared to be the only neuronal population that expressed the HuC/D antigens in the whole embryo. ⋯ HuC/D immunopositivity persisted until stage 30 HH (about 6.5 days), the later developmental stage investigated in this study, when colocalization with GnRH was detected. Negativity to the anti-proliferating cell nuclear antigen (anti-PCNA) immunostaining, a marker of S-phase, showed that migratory olfactory cells have left the mitotic cycle. Altogether, these results suggest that we have identified the first population of post-mitotic neurons in the developing nervous system of the chick embryo.
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Comparative Study
Brain afferents to the lateral caudal ventrolateral medulla: a retrograde and anterograde tracing study in the rat.
The ventrolateral medulla (VLM) modulates autonomic functions, motor reactions and pain responses. The lateralmost part of the caudal VLM (VLMlat) was recently shown to be the VLM area responsible for pain modulation. In the present study, the brain sources of VLMlat afferent fibers were determined by tract-tracing techniques. ⋯ The present study gives an account of the brain regions putatively involved in triggering the modulatory actions elicited from the VLMlat. These include areas committed to somatosensory processing, autonomic control, somatic and visceral motor activity and affective reactions. The findings suggest that the VLMlat may play a major homeostatic role in the integration of nociception with other brain functions.
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Comparative Study
Sexual dimorphism in the contribution of protein kinase C isoforms to nociception in the streptozotocin diabetic rat.
The contribution of second messenger signaling, glucose level and sex hormones to sexual dimorphism in the streptozotocin model of diabetic painful peripheral neuropathy was evaluated. Streptozotocin induced elevation of blood glucose and mechanical hyperalgesia (measured by the Randall-Selitto paw-withdrawal test) were both greater in female rats. Ovariectomy abolished and estrogen implants reconstituted this sexual dimorphism; gonadectomy in males had no effect. ⋯ Inhibitors of protein kinase A, protein kinase C (non-selective), protein kinase G and nitric oxide synthase attenuated hyperalgesia equally in both sexes. Higher blood glucose levels in diabetic females were also sex hormone dependent, and magnitude of hyperalgesia correlated with blood glucose level in diabetic male and female rats. These results demonstrate sexual dimorphism in diabetic hyperalgesia, mediated by sex hormone dependent differences in protein kinase Cepsilon and protein kinase Cdelta signaling and blood glucose levels and suggest that sex may be an important factor to be considered in the treatment of symptomatic diabetic neuropathy.
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Comparative Study
Neuroprotective activity of antazoline against neuronal damage induced by limbic status epilepticus.
Imidazoline drugs exert neuroprotective effects in cerebral ischaemia models. They also have effects against mouse cerebellar and striatal neuronal death induced by N-methyl-D-aspartate (NMDA) through the blockade of NMDA currents. Here, we investigated the effects of antazoline on NMDA toxicity and current in rat hippocampal neuronal cultures, and on an in vivo model of status epilepticus. ⋯ On the contralateral side to the pilocarpine injection, only the hippocampal CA3 area was significantly protected in the low-dose group, but all investigated structures were in the high-dose group. In conclusion, antazoline is a potent neuroprotective drug in different models of neuronal primary culture, as previously shown in striatal and cerebellar granule neurons [Neuropharmacology 39 (2000) 2244], and here in hippocampal neurons. Antazoline is also neuroprotective in vivo in the intra-pyriform pilocarpine-induced status epilepticus model.