The Journal of neuroscience : the official journal of the Society for Neuroscience
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Studies suggest that pain may play a major role in determining cortical rearrangements in the adult human somatosensory system. Most studies, however, have been performed under conditions whereby pain coexists with massive deafferentation (e.g., amputations). Moreover, no information is available on whether spinal and brainstem changes contribute to pain-related reorganizational processes in humans. ⋯ This right-left asymmetry was absent after stimulation of the patients' middle fingers and in control subjects. Results suggest that chronic cervical radicular pain is associated with changes in neural activity at multiple levels of the somatosensory system. The absence of correlation between the amplitude of spinal, brainstem, and cortical components of SEPs suggests that enhancement of cortical activity is not a simple amplification of subcortical enhancement.
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The transcription factor DeltaFosB is induced in the hippocampus and other brain regions by repeated electroconvulsive seizures (ECS), an effective antidepressant treatment. The unusually high stability of this protein makes it an attractive candidate to mediate some of the long-lasting changes in the brain caused by ECS treatment. To understand how DeltaFosB might alter brain function, we examined the gene expression profiles in the hippocampus of inducible transgenic mice that express DeltaFosB in this brain region by the use of cDNA expression arrays that contain 588 genes. ⋯ A 1.6 kb fragment of the cdk5 promoter was cloned, and activity of the promoter was found to be increased after overexpression of DeltaFosB in cell culture. Moreover, mutation of the single consensus activator protein-1 site contained within the cdk5 promoter fragment completely abolished activation of the promoter by DeltaFosB. Together, these results suggest that cdk5 is one target by which DeltaFosB produces some of its physiological effects in the hippocampus and thereby mediates certain long-term consequences of chronic ECS treatment.
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Experimental evidence supporting 1,1'-dimethyl-4,4'-bipyridinium [paraquat (PQ)] as a risk factor for Parkinson's disease (PD) is equivocal. Other agricultural chemicals, including dithiocarbamate fungicides such as manganese ethylenebisdithiocarbamate [maneb (MB)], are widely used in the same geographical regions as paraquat and also impact dopamine systems, suggesting that mixtures may be more relevant etiological models. This study therefore proposed that combined PQ and MB exposures would produce greater effects on dopamine (DA) systems than would either compound administered alone. ⋯ Reactive gliosis occurred only in response to combined PQ + MB in dorsal-medial but not ventral striatum. TH immunoreactivity and cell counts were reduced only by PQ + MB and in the substantia nigra but not ventral tegmental area. These synergistic effects of combined PQ + MB, preferentially expressed in the nigrostriatal DA system, suggest that such mixtures could play a role in the etiology of PD.
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The physiological actions of neurotransmitter receptors are intimately linked to their proper neuronal compartment localization. Here we studied the effect of the metabotropic glutamate receptor (mGluR)-interacting proteins, Homer1a, b, and c, in the targeting of mGluR5 in neurons. We found that mGluR5 was exclusively localized in cell bodies when transfected alone in cultured cerebellar granule cells. ⋯ Depolarization of the neurons with a mixture of ionotropic glutamate receptor agonists, NMDA and kainate, or potassium channel blockers, tetraethylammonium and 4-aminopyridine, induced transient expression of endogenous Homer1a and persistent neuritic localization of transfected mGluR5 even long after degradation of Homer1a. These results suggest that Homer1a/b/c proteins are involved in the targeting of mGluR5 to dendritic synaptic sites and/or axons and that this effect can be regulated by neuronal activity. Because the activity-dependent effect of endogenous Homer1a was also long-lasting, the axonal targeting of mGluR5 by this protein is likely to play an important role in synaptic plasticity.
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Although both pre- and postsynaptic mechanisms have been implicated in the analgesia produced by mu-opioids at the spinal cord, it is not known under what conditions these different controls come into play. Because the mu-opioid receptor (MOR) can be visualized in individual lamina II excitatory interneurons and internalizes into endosomes on ligand binding, we tested whether MOR internalization could be monitored and used to measure postsynaptic MOR signaling. To test whether endogenous opioids modulate these lamina II interneurons during noxious stimulation, we next assessed the magnitude of postsynaptic MOR internalization under a variety of nociceptive conditions. ⋯ We found, however, that noxious stimuli, under normal or inflammatory conditions, did not induce MOR internalization. Thus, endogenous enkephalins and endomorphins, thought to be released during noxious peripheral stimuli, do not modulate nociceptive messages via postsynaptic MORs on lamina II interneurons. We suggest that any endogenous opioids that are released by noxious stimuli target presynaptic MORs or delta-opioid receptors.