Neuroscience
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Human obesity is associated with increased leptin levels and pain, but the specific brain regions and neurochemical mechanisms underlying this association remain poorly understood. This study used adult male C57BL/6J (B6, n=14) mice and leptin-deficient, obese B6. Cg-Lep(ob)/J (obese, n=10) mice to evaluate the hypothesis that nociception is altered by systemic leptin levels and by adenosine A₁ receptors in the pontine reticular formation. ⋯ Microinjection of SMLA into the pontine reticular formation before SPA did not alter PWL. The results show for the first time that pontine reticular formation administration of the adenosine A₁ receptor agonist SPA produced antinociception only in the presence of systemic leptin. The concentration-response data support the interpretation that adenosine A₁ receptors localized to the pontine reticular formation significantly alter nociception.
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State-dependent neuronal firing patterns reflect changes in ongoing information processing and cortical function. A disruption of neuronal coordination has been suggested as the neural correlate of anesthesia. Here, we studied the temporal correlation patterns of ongoing spike activity, during a stepwise reduction of the volatile anesthetic desflurane, in the cerebral cortex of freely moving rats. ⋯ Paradoxically, in 4 of 8 animals, HI correlation was also high at the deepest level of anesthesia (8%) when local field potentials (LFP) were burst-suppressed. We conclude that recovery from desflurane anesthesia is accompanied by a graded defragmentation of neuronal activity in the cerebral cortex. Hypersynchrony during deep anesthesia is an exception that occurs only with LFP burst suppression.
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The latest advancements in neurobiological research provide increasing evidence that inflammatory and neurodegenerative pathways play an important role in depression. According to the cytokine hypothesis, depression could be due to the increased production of pro-inflammatory cytokines by microglia activation. Thus, using the BV-2 microglial cell line, the aim of the present study was to investigate whether fluoxetine (FLX) or acetylsalicylic acid (ASA) could inhibit this microglia activation and could achieve better results in combination. ⋯ Moreover, FLX could inhibit phosphorylation of nuclear factor-κB (NF-κB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK), and the combined use with ASA could enhance these effects. Notably, the adjunctive agent ASA could also inhibit phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2). Taken together, our results suggest that FLX may have some anti-inflammatory effects by modulating microglia activation and that ASA served as an effective adjunctive agent by enhancing these therapeutic effects.
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The heterozygous reeler mouse (HRM), haploinsufficient for reelin, shares several neurochemical and behavioral similarities with patients suffering from schizophrenia. It has been shown that defective reelin signaling influences the mesolimbic dopaminergic pathways in a specific manner. However, there is only little information about the impact of reelin haploinsufficiency on the monoaminergic innervation of different brain areas, known to be involved in the pathophysiology of schizophrenia. ⋯ Overall, no genotype differences were found in the 5-HT-IR fiber densities. In conclusion, these results support the view that reelin haploinsufficiency differentially influences the catecholaminergic (esp. dopaminergic) systems in brain areas associated with schizophrenia. The reelin haploinsufficient mouse may provide a useful model for studying the role of reelin in hippocampal dysfunction and its effect on the dopaminergic system as related to schizophrenia.
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Depression is among the most debilitating diseases worldwide. Long-term exposure to stressors plays a major role in development of human depression. Chronic mild stress (CMS) seems to be a valid animal model for depression. ⋯ The results also suggest a possible role of edema or inflammation concerning the brain morphology in CMS rats. The overall finding using DTI suggests there might be a major role of loss of myelin sheath, which leads to disrupted connectivity between the limbic area and the prefrontal cortex during the onset of depression. Our findings indicate that interpretation of these indices may provide crucial information about the type and severity of mood disorders.