Neuroscience
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We previously reported that a permanent transection of adult rat sciatic and hypoglossal nerves resulted in distinct changes in the levels of both low-affinity nerve growth factor receptor (p75) and choline acetyltransferase in the corresponding motoneurons as determined by immunoreactivity. Permanent axotomy of hypoglossal motoneurons induced a progressive loss of choline acetyltransferase immunoreactivity and a persistent expression of p75 immunoreactivity, phenomena that were not observed in spinal motoneurons. These observations indicated that spinal and brainstem motoneurons respond to permanent axotomy with a differential immunoreactivity for p75 and choline acetyltransferase. ⋯ In addition, viable sciatic grafts decreased the number of p75 immunoreactive hypoglossal motoneurons both at seven and at 30 days. In conclusion, the effects of viable sciatic grafts on the number of choline acetyltransferase and p75-labelled hypoglossal motoneurons indicate that these adult neurons are able to respond to factors released from the sciatic nerve, and that the number of injured motoneurons positive for choline acetyltransferase and p75 can be influenced by the presence of factors that may reach their proximal stumps. Furthermore, we hypothesize that the differential expression patterns between hypoglossal and sciatic motoneurons may be due, at least in part, to factors released from the nerve trunks themselves.
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In order to elucidate the mechanism(s) of neuronal protection by hypothermia against ischemic damage, we examined the effect of lowering temperature on the microglial activation that is thought to cause the development of ischemia-induced neuronal damages. Cultured microglia from neonatal rats were measured for microglial activation by the following indices: production of superoxide and nitric oxide by the methods of acetyl-cytochrome c reduction and nitrite accumulation in the culture medium, respectively, and cell proliferation evaluated by [3H]thymidine uptake. At 30 degrees C, superoxide production induced by phorbol ester was approximately as low as 30% of the control at 37 degrees C, and nitric oxide production after addition of lipopolysaccharide was decreased to approximately 25% of the control. ⋯ In addition, the proliferation of microglia was remarkably inhibited at 30 degrees C. The level of proliferation in the hypothermic condition is much lower in microglia (14% of the control) than those in astrocytes cultured from brain cortices (96%) and fibroblasts cultured from brain meninges (53%), suggesting that the microglial activation is highly susceptible to lowering temperature. The present study indicates that hypothermia potently inhibits proliferation, superoxide and nitric oxide production of cultured microglia and that the hypothermic protection against postischemic neuronal damage might be, at least in part, due to the suppression of microglial activation.
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The expression of the transcription factor c-JUN was investigated in the rat fascia dentata under normal conditions and after entorhinal cortex lesion. As shown by immunocytochemistry and in situ hybridization histochemistry c-JUN and its messenger RNA are present in the principal cell layers of the dentate gyrus and Ammon's horn (except hippocampal region CA2). Pre-embedding immunogold electron microscopy revealed an almost exclusive nuclear localization of c-JUN, where it is associated with chromatin. ⋯ These results point to a specific role of c-JUN in the granule cells of the fascia dentata in the normal animal and in rats with entorhinal cortex lesions. The selective induction of c-JUN after entorhinal lesion could be one of the first molecular steps that regulate transneuronal changes within granule cells after their denervation. A different mechanism has to be assumed for GABAergic interneurons known to receive an entorhinal innervation as well.
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Nociceptin (a heptadecapeptide also known as orphanin FQ) is a potent endogenous agonist of the opioid receptor-like1 receptor and has a sequence similar to dynorphin A. It has been reported that intracerebroventricularly injected nociceptin produced hyperalgesia in mice and that intrathecal injection of nociceptin inhibits the spinal sensitization. In the present study, we investigated the effect of intrathecally administered nociceptin in the rat formalin test (a model of inflammatory pain) and the rat hot plate test. ⋯ These effects of nociceptin were not antagonized by the co-administration of naloxone. Intrathecal injection of nociceptin had no effect on the hot plate test. These data suggest that nociceptin plays an important role in spinal nociceptive transmission through the activation of a naloxone-insensitive receptor, and spinally administered nociceptin produces an analgesic effect during the rat formalin test, but not the hot plate test.
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Tight ligation of the fifth and sixth lumbar segmental nerves in the rat provides a model of neuropathic pain. We used this model to assess the changes in primary afferent input to the dorsal horn in neuropathic pain syndromes. Dorsal roots and ganglia were examined for up to 32 weeks following segmental nerve ligation. ⋯ These findings indicate that although there is a great loss of dorsal root ganglion cells, there is dramatic sprouting of myelinated fibres and possibly some sprouting of unmyelinated fibres in the dorsal roots. Additionally, a difference in the responses of unmyelinated and myelinated fibres to this peripheral nerve injury is revealed. These changes in dorsal root ganglion cells and their central axons may underlie certain aspects of abnormal pain syndromes because of changes in the types and quantity of input the dorsal horn receives.