Neuroscience
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Interactions of glutamatergic and purinergic actions in the medulla regulate important cardiovascular functions. The glutamatergic action in dorsal facial area (DFA) of the medulla increases blood flow of common carotid artery (CCA) in cats. We hypothesized that interactions of glutamatergic and purinergic actions in the DFA may regulate the CCA blood flow. ⋯ Nevertheless, P1 receptor agonist induced only mild and poorly reproducible increase in the CCA blood flow. In conclusion, prominent P2 and minor P1 purinergic receptors appear to be present in the DFA; the purinergic activation can mediate a release of glutamate that stimulates NMDA and AMPA to induce the increase of the CCA blood flows. These findings may provide important information for developing therapeutic strategy for diseases involving the CCA blood flow, such as hypertensive disease and cerebral ischemia.
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Human immunodeficiency virus-1 (HIV-1) infection may produce neurological deficits, such as cognitive decline, that may be worsened by concurrent ethanol (EtOH) abuse. Among the many biochemical cascades likely mediating HIV-1-associated neuronal injury is enhancement of N-methyl-d-aspartate (NMDA) receptor function and progression to excitotoxicity, an effect that may be directly or indirectly related to accumulation in brain of the HIV-1 trans-activator of transcription (Tat) factor. The present studies were designed to examine the hypothesis that binge-like EtOH pre-exposure would enhance effects of Tat on NMDA receptor function. ⋯ No changes in [(3)H]MK-801 binding were observed. Binding density of [(3)H]PK11195, a ligand for peripheral benzodiazepine receptors expressed on activated microglia, was elevated proximal to cannula tracks in all animals, but was not altered by EtOH or Tat exposure. These findings suggest that EtOH abuse and/or dependence in HIV-positive individuals may promote HIV-1-associated cognitive deficits by altering NMDA receptor function in the absence of microglial activation or neuroinflammation.
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Dysfunctions of the brain 5-HT system are often associated with affective disorders, such as depression. The raphe nuclei target the limbic system and most forebrain areas and constitute the main source of 5-HT in the brain. All 5-HT neurons express tryptophan hydroxylase-2 (TPH2), the brain specific, rate-limiting enzyme for 5-HT synthesis. ⋯ No behavioral differences were found in the OF or on the EPM. These data indicate that ER beta acts at the level of the rat DRN to modulate tph2 mRNA expression and thereby influence 5-HT synthesis in DRN subregions. Our results also suggest that local activation of ER beta neurons in the DRN may be sufficient to decrease despair-like behavior, but not anxiolytic behaviors.
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Little is known about the G protein-coupled receptor desensitization process during pregnancy. Wistar pregnant rats were treated with (-)N(6)-phenylisopropyladenosine (R-PIA), an adenosine A(1) receptor (A(1)R) agonist, in their drinking water during pregnancy, and the effect on A(1)R/adenylyl cyclase system was studied in both maternal and fetal brain. In maternal brain, binding assays revealed a significant decrease in total receptor numbers in plasma membranes (27%, P<0.05), with no significant changes in receptor affinity. ⋯ On the other hand, forskolin- and forskolin-plus guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S)-stimulated adenylyl cyclase activity was decreased in maternal (P<.01) and fetal brain (P<.001). Furthermore, adenylyl cyclase inhibition elicited by N(6)-cyclohexyladenosine (CHA), a selective A(1)R agonist, was significantly decreased in both maternal (P<0.05) and fetal brain (P<.01), suggesting a desensitization of the A(1)R/adenylyl cyclase pathway. Therefore, these results suggest that R-PIA intake during pregnancy causes desensitization of the A(1)R-mediated inhibitory transduction pathway in both maternal and fetal brain, probably due to the decreased density of A(1)R at the cell surface.
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Retinal bipolar cells relay visual information from photoreceptors to third-order retinal neurons. Bipolar cells, comprising multiple types, play an essential role in segregating visual information into multiple parallel pathways in the retina. The identification of molecular markers that can label specific retinal bipolar cells could facilitate the investigation of bipolar cell functions in the retina. ⋯ GFP expression in retinal cone bipolar cells was seen as early as postnatal day 5. In addition, despite severe retinal degeneration due to the presence of the rd1 mutation in this transgenic line, the density of GFP-labeled cone bipolar cells remained stable up to at least 6 months of age. This transgenic mouse line will be a useful tool for the study of type 4 cone bipolar cells in the retina under both normal and disease conditions.