Neuroscience
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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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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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Although gender differences in the response to stress have been reported, differences in stress-induced changes in feeding behavior have not been well studied. In this report, inhibition of food intake was compared in male and female rats following 1 h of restraint, electric footshock, or emotional stress induced by a communication box. Although the three stressors inhibited food intake in both genders, only emotional stress caused a gender difference, a greater inhibition of food intake in female rats (48%) than in male rats (22%). ⋯ Ovariectomy reduced the inhibition of food intake by emotional stress to the same level as that in male, and replacement with estradiol restored the inhibition to the level of the normal female rats. A corticotropin-releasing factor (CRF) type 1 receptor antagonist prevented emotional stress-induced inhibition of food intake, indicating the involvement of CRF type 1 receptor in emotional stress-induced inhibition of food intake. These results suggest that female rats show a greater inhibition of food intake in response to emotional stress than male rats and that estrogen plays a role in the gender difference.
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We have previously shown that voluntary exercise produces enhanced neurogenesis and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In the present experiments we show that rats given access to a running wheel (Runners) exhibit significantly more short-term potentiation and LTP with theta-patterned conditioning stimulation in vivo than do age-matched litter mates (Controls). This increase in LTP appears to reflect an alteration in the induction threshold for synaptic plasticity that accompanies voluntary exercise. ⋯ Consistent with these findings, we found that mRNA levels for NR2B subtype of NMDA receptor were increased specifically in the DG of Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF) and glutamate receptor 5 mRNA levels were also significantly elevated in the DG of Runners, but not in other areas of the hippocampus. Thus, alterations in the expression of BDNF, and specific glutamate receptor subtypes, may underlie the ability of exercise to enhance neurogenesis and reduce the threshold for LTP in the DG.