Neuroscience
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Comparative Study
A 14-day period of hindpaw sensory deprivation enhances the responsiveness of rat cortical neurons.
Hypodynamia-hypokinesia (HH) is a model of hindpaw sensory deprivation. It is obtained by unloading of the hindquarters during 14 days. In this situation, the feet are not in contact with the ground and as a consequence, the cutaneous receptors are not activated; the sensory input to the primary somatosensory cortex (SmI) is thus reduced. ⋯ Thin-spike cells were less frequently encountered in HH than in control rats. The analysis of regular cells revealed that after HH (1) spontaneous activity was unchanged and (2) cortical somatosensory neurons were more responsive: the cutaneous threshold was reduced and the response magnitude increased. Taken together, these results suggest a down-regulation of GABAergic function.
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Comparative Study
Association of gephyrin and glycine receptors in the human brainstem and spinal cord: an immunohistochemical analysis.
Gephyrin is a postsynaptic clustering molecule that forms a protein scaffold to anchor inhibitory neurotransmitter receptors at the postsynaptic membrane of neurons. Gephyrin was first identified as a protein component of the glycine receptor complex and is also colocalized with several GABAA receptor subunits in rodent brain. We have studied the distribution of gephyrin and glycine receptor subunits in the human brainstem and spinal cord using immunohistochemistry at light and confocal laser scanning microscopy levels. ⋯ Colocalization of immunoreactivities for gephyrin and glycine receptor subunits was detected in the dorsal and ventral horns of the spinal cord, the hypoglossal nucleus and the medial vestibular nucleus of the medulla. The results clearly establish that gephyrin is ubiquitously distributed and is colocalized, with a large proportion of glycine receptor subunits in the human brainstem and spinal cord. We therefore suggest that gephyrin functions as a clustering molecule for major subtypes of glycine receptors in the human CNS.
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It is known that the level of activity in nociceptive primary afferent nerve fibers increases in neuropathic conditions that produce pain, but changes in the temporal patterning of action potentials have not been analyzed in any detail. Because the patterning of action potentials in sensory nerve fibers might play a role in the development of pathological pain states, we studied patterning of mechanical stimulus-evoked action potential trains in nociceptive primary afferents in a rat model of vincristine-induced painful peripheral neuropathy. Systemic administration of vincristine (100 microg/kg) caused approximately half the C-fiber nociceptors to become markedly hyperresponsive to mechanical stimulation. ⋯ Variability in the temporal pattern of action potential firing was quantified by determining the coefficient of variability (CV2) for adjacent interspike intervals. This analysis revealed that vincristine altered the pattern of action-potential timing, so that combinations of higher firing frequency and higher variability occurred that were not observed in control fibers. The abnormal temporal structure of nociceptor responses induced by vincristine in some C-fiber nociceptors could contribute to the pathogenesis of chemotherapy-induced neuropathic pain, perhaps by inducing activity-dependent post-synaptic effects in sensory pathways.
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Comparative Study
N-methyl-D-aspartate-induced excitation and sensitization of normal and inflamed nociceptors.
The present study investigates the contribution of peripheral N-methyl-D-aspartate (NMDA) receptors to acute nociception and persistent inflammatory pain in the rat. Immunohistochemical localization of the NMDA receptor one (NMDAR1) subunit demonstrates that 47% of unmyelinated axons in the normal digital nerve are positively labeled. In concert with the overall progression of inflammation following injection of complete Freund's adjuvant (CFA) in the hind paw, a significant increase in the proportion of NMDAR1-labeled unmyelinated digital axons occurs at 2 and 7, but not 14 days following hind-paw inflammation. ⋯ Exposure of nociceptors in normal skin to 1 mM NMDA sensitizes the units to reapplication of NMDA and to heat. Nociceptors that demonstrate sensitization to heat in persistent inflammation show an enhanced sensitization when exposed to exogenous NMDA. Thus, peripheral NMDA receptors not only play an important role in modulating the responses of nociceptors in normal skin, but their upregulation and activation on peripheral nociceptors contributes significantly to the mechanical sensitivity and heat sensitization that accompanies persistent inflammation.
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Comparative Study
Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer's disease patients.
Dendritic spines are postsynaptic sites of excitatory input in the mammalian nervous system. Apolipoprotein (apo) E participates in the transport of plasma lipids and in the redistribution of lipids among cells. A role for apoE is implicated in regeneration of synaptic circuitry after neural injury. ⋯ These age dependent differences in the effects of apoE isoforms on neuronal integrity may relate to the increased risk of dementia in aged individuals with the apoE4 allele. Significantly in human brain, apoE4 dose correlated inversely with dendritic spine density of DG neurons cell in the hippocampus of both AD (P=0.0008) and aged normal controls (P=0.0015). Our findings provide one potential explanation for the increased cognitive decline seen in aged and AD patients expressing apoE4.