Neuroscience
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The expression of c-jun, mitogen-activated protein kinase phosphatase-1 (mkp-1), caspase-3 and glial fibrillary acidic protein (gfap) was examined at 1, 3 and 7 days after cortical cold injury in rats by in situ hybridisation and immunocytochemistry. Alterations of gene expression were related to metabolic disturbances and delayed cell death, as revealed by cerebral protein synthesis autoradiography, ATP bioluminescence, pH fluorescence and terminal transferase biotinylated dUTP nick end labelling (TUNEL). Protein synthesis autoradiographies depicted sharply demarcated cortex lesions, which were almost congruent with areas exhibiting ATP depletion (lesion volume: 16.9+/-11.8 mm(3) after 7 days). ⋯ Gfap mRNA was elevated in all regions exhibiting tissue alkalosis. Our data suggest that delayed cell injury after cortex trauma may be apoptotic in the ventrobasal thalamus, but not the peri-lesion rim. The dissociated responses of c-jun, mkp-1 and caspase-3 mRNAs may represent important factors influencing tissue viability.
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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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In the lamprey, spinal locomotor activity can be initiated by pharmacological microstimulation in several brain areas: rostrolateral rhombencephalon (RLR); dorsolateral mesencephalon (DLM); ventromedial diencephalon (VMD); and reticular nuclei. During DLM- or VMD-initiated locomotor activity in in vitro brain/spinal cord preparations, application of a solution that focally depressed neuronal activity in reticular nuclei often attenuated or abolished the locomotor rhythm. Electrical microstimulation in the DLM or VMD elicited synaptic responses in reticulospinal (RS) neurons, and close temporal stimulation in both areas evoked responses that summated and could elicit action potentials when neither input alone was sufficient. ⋯ These new results suggest that neurons in the RLR project rostrally to locomotor areas in the DLM and VMD. These latter areas then appear to project caudally to RS neurons, which probably integrate the synaptic inputs from both areas and activate the spinal locomotor networks. These pathways are likely to be important components of the brain neural networks for the initiation of locomotion and have parallels to locomotor command systems in higher vertebrates.