Neuroscience
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AMPA receptor GluA2 subunits are strongly implicated in cognition, and prior work suggests that these subunits may be regulated by atypical protein kinase C (aPKC) isoforms. The present study assessed whether hippocampal and cortical AMPA receptor GluA2 subunit regulation may be an underlying factor in known age-related differences to cognitive-impairing doses of ethanol, and if aPKC isoforms modulate such responses. Hippocampal AMPA receptor GluA2 subunit, protein kinase Mζ (PKMζ), and PKCι/λ expression were elevated during adolescence compared to adults. 1 h following a low-dose (1.0-g/kg) ethanol exposure, hippocampal AMPA receptor GluA2 subunit serine 880 phosphorylation was decreased in adolescents, but was increased in adults. ⋯ However, no demonstrable effects were found following a low-dose ethanol exposure at either age. High-dose ethanol exposure reduced adolescent GluA2 subunit phosphorylation and aPKC isoform expression that were again accompanied by delayed reductions in synaptosomal GluA2 subunit expression. Together, these results suggest that GluA2-containing AMPA receptor modulation by aPKC isoforms is age-, region- and dose-dependently regulated, and may potentially be involved in developmentally regulated ethanol-induced cognitive impairment and other ethanol behaviors.
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GABAB receptors associate with Gi/o-proteins that regulate voltage-gated Ca(2+) channels and thus the intracellular Ca(2+) concentration ([Ca(2+)]i), there is also reported cross-regulation of phospholipase C. These associations have been studied extensively in the brain and also shown to occur in non-neural cells (e.g. human airway smooth muscle). More recently GABAB receptors have been observed in chick retinal pigment epithelium (RPE). ⋯ Baclofen-induced increases in the [Ca(2+)]i were attenuated by pre-treatment with CGP46381, pertussis toxin, and U73122. GABAB1 and GABAB2 are co-expressed in cell cultures of human RPE. GABAB receptors in RPE regulate the [Ca(2+)]i via a Gi/o-protein and phospholipase C pathway.
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Lipoprotein lipase (LPL) is expressed at high levels in hippocampal neurons, although its function is unclear. We previously reported that LPL-deficient mice have learning and memory impairment and fewer synaptic vesicles in hippocampal neurons, but properties of synaptic activity in LPL-deficient neurons remain unexplored. ⋯ Moreover, lipid assay revealed deficient docosahexaenoic acid (DHA) and arachidonic acid (AA) in the hippocampus of LPL-deficient mice; exogenous DHA or AA supplement partially restored synaptic vesicle recycling capability. These results suggest that impaired synaptic vesicle recycling results from deficient DHA and AA and contributes to the presynaptic dysfunction and plasticity impairment in LPL-deficient neurons.
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Previous work has shown a reduction of apical dendritic length and spine density in neurons from the CA1 hippocampus subfield of spontaneously hypertensive rats (SHRs). These abnormalities are prevented by treatment for 2 weeks with 17β-estradiol. In view of the fact that diabetes and hypertension are comorbid diseases, we have now studied the effect of Streptozotocin-induced diabetes on the dendritic tree and spines of CA1 hippocampus neurons, and also compared the regulation of these parameters by 17β-estradiol in diabetic and normoglycemic SHR. ⋯ Treatment with 17β-estradiol of diabetic SHR enhanced dendritic length, increased dendritic spine density and further decreased BP. Thus, changes of cytoarchitecture of CA1 neurons due to 17β-estradiol treatment of normoglycemic SHR persisted after diabetes induction. A decrease of BP may also contribute to the central effects of 17β-estradiol in SHR diabetic rats.
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Binding of bacterial lipopolysaccharides (LPS) to toll-like receptor 4 (TLR4) triggers an innate immunoresponse associated with pain and inflammation. The expression, and to a greater extent the regulation of TLR4 and its auxiliary proteins (myeloid differentiation protein 1 (MD1), myeloid differentiation protein 2 (MD2) and cluster of differentiation 14 (CD14)), are both poorly understood in trigeminal and nodose neurons. We used a combination of Western blotting, semi-quantitative polymerase chain reaction (PCR), pharmacological manipulation and immunohistochemistry. ⋯ Also we observed that in both neuronal types LPS acutely (within 20 min) down-regulated CD14 and MD2 mRNAs. In addition, LPS increased significantly the proportion of trigeminal and nodose neurons expressing nociceptin/orphanin FQ in culture probably acting via TLR4/MD2. Although the exact mechanisms underlying the regulation by trophic factors and LPS require further elucidation, the findings of this study indicate that LPS acts through its archetypical receptor in trigeminal and nodose neurons.