Neuroscience
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The primary visual (V1), auditory (AI), and somatosensory (SI) cortices are reciprocally connected with their respective sensory association cortices. In the rat, we have previously demonstrated that some of the connections arising from the secondary somatosensory (SII) and parietal insular (PA) cortices and terminating in the SI, are characterized by the expression of latexin, a candidate protein of carboxypeptidase A inhibitor. Here, by using retrograde tracing and latexin-immunohistochemistry, we show that latexin-expressing neurons in other association cortices of different sensory modalities also contribute to the feedback projections to the corresponding primary sensory cortices. ⋯ In contrast to feedback connections, far fewer latexin-expressing neurons participate in callosal or intrahemispheric feedforward connections. The latexin-expressing neurons constitute a virtually completely different population from corticothalamic neurons within the infragranular layers. Given that latexin might participate in the modulation of neuronal activity by controlling the protease activity, latexin-expressing feedback pathways would play a unique role in the modulation of sensory perception.
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Tg2576 transgenic mice (mice overexpressing the "Swedish" mutation in the human amyloid precursor protein 695) demonstrated a decreased capacity for cell proliferation in the dentate gyrus of the hippocampus compared with non-transgenic littermates at 3 months, 6 months and 9 months of age. Isolation stress induced by individually housing each mouse from the time of weaning further decreased hippocampal cell proliferation in Tg2576 mice as well as in non-transgenic littermates at 6 months of age. Decreases in hippocampal cell proliferation in isolated Tg2576 mice were associated with impairments in contextual but not cued memory. ⋯ These results suggest that Tg2576 mice, a mouse model of Alzheimer disease, have an impaired ability to generate new cells in the dentate gyrus of the hippocampus and that the magnitude of this impairment can be modulated by behavioral interventions and drugs known to have effects on hippocampal neurogenesis in normal rodents. Unexpectedly, isolation stress also appeared to accelerate the underlying process of beta-amyloid plaque deposition in Tg2576 mice. These results suggest that stress may have an impact on the underlying disease process associated with Alzheimer's disease.
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The expression of mRNA encoding for the 67 kilodalton isoform of glutamate decarboxylase (GAD67) was examined by in situ hybridization histochemistry in the entopeduncular nucleus (EP) of adult rats with a 6-hydroxydopamine unilaterally lesion of dopamine neurons. Our results provide original evidence that continuous or intermittent levodopa administration is equally effective at reversing the lesion-induced increase in GAD67 mRNA expression in the EP when compared with vehicle controls. To characterize the GABAergic interactions that may mediate levodopa-induced alterations in the EP, double-labeling in situ hybridization was conducted with a combination of GAD67 radioactive and preproenkephalin or preprotachykinin digoxigenin-labeled complementary RNA probes in the striatum. ⋯ Continuous levodopa failed to alter striatal GAD67 mRNA levels, or the number or affinity of GABA(A) receptors when compared with vehicle-treated controls. These results suggest the normalization of GAD gene expression in the EP by intermittent levodopa involves an increase in GABAergic inhibition by striatonigral/EP neurons of the direct pathway. Conversely, the effects of continuous levodopa on GAD mRNA levels in the EP do not appear to be mediated by GABA.
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Stress and stress-related hormones induce structural changes in neurons of the adult CNS. Neurons in the hippocampus, the amygdala and the prefrontal cortex undergo neurite remodeling after chronic stress. In the hippocampus some of these effects can be mimicked with chronic administration of adrenal steroids. ⋯ While chronic stress increases the number of PSA-NCAM- and DCX-immunoreactive cells in the piriform cortex layer II, chronic corticosterone administration decreases these numbers. These findings indicate that stress and adrenal steroids affect the piriform cortex and suggest that in this region, as in the hippocampus, they may induce structural changes. This is a potential mechanism by which stress and corticosterone modulate functions of this limbic region, such as its participation in olfactory memory.
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Long-term GABA(A) receptor alterations occur in hippocampal dentate granule neurons of rats that develop epilepsy after status epilepticus in adulthood. Hippocampal GABA(A) receptor expression undergoes marked reorganization during the postnatal period, however, and the effects of neonatal status epilepticus on subsequent GABA(A) receptor development are unknown. ⋯ Further, unlike adult rats, postnatal day 10 rats subjected to status epilepticus do not become epileptic. These findings suggest age-dependent differences in the effects of status epilepticus on hippocampal GABA(A) receptors that could contribute to the selective resistance of the immature brain to epileptogenesis.