Neuroscience
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Age-related testosterone depletion in men is a risk factor for Alzheimer's disease (AD). How testosterone modulates AD risk remains to be fully elucidated, although regulation of tau phosphorylation has been suggested as a contributing protective action. To investigate the relationship between testosterone and tau phosphorylation, we first evaluated the effect of androgen status on tau phosphorylation in 3xTg-AD mice. ⋯ Additional experiments demonstrated androgen-induced changes in Akt, GSK3β and tau phosphorylation in AR-expressing PC12 cells but not in AR-negative PC12 cells. Together, these results suggest an AR-dependent pathway involving PI3K-Akt-GSK3β signaling through which androgens can reduce tau phosphorylation. These findings identify an additional protective mechanism of androgens that can improve neural health and inhibit development of AD.
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Sepsis-associated encephalopathy (SAE) has close association with long-term cognitive deficits, resulting in increased mortality. The mechanism of SAE is complicated, including excessive microglial activation and neuroinflammation. Cannabinoid type 2 receptor (CB2R) has been proved to be effective in neuronal protection and survival promotion. ⋯ Conclusion from these results, we conclude that CLP could induce microglia hyperactivation and neuronal pyroptosis, aggravating brain tissue destruction and cognitive dysfunction. The CB2R-specific agonist HU308 could have protective effects against SAE by inhibiting microglia activity and neuronal pyroptosis. This study provides a new therapeutic option for the treatment of SAE.
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There is a high level of comorbidity between depression and alcohol use disorder. Subanesthetic doses of ketamine induce short-acting and enduring antidepressant effects after a single or a few administrations. Considering such comorbidity, we assessed, in Swiss male mice, if ketamine-induced antidepressant-like effects would alter ethanol's rewarding effects; and, if ethanol pretreatment would alter the rewarding and antidepressant effects of ketamine. ⋯ Ketamine (50 mg/kg) induced hippocampal downregulation of 145 kDa TrkB may contribute to ketamine-induced antidepressant tolerance. Likewise, a relationship between low hippocampal levels of p75NTR in the Ethanol-Ketamine (50 mg/kg) and ketamine-induced CPP blockade may be considered. The findings underscore potential ethanol-ketamine interactions likely to undermine ketamine putative antidepressant effects.
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The palatability and concentration of sweet foods promote hedonic feeding beyond homeostatic need. Understanding how neurons respond to sweet taste is thus of great importance. The dorsomedial nucleus accumbens shell (dNAcMed) is considered a "sensory sentinel," promoting hedonic feeding. ⋯ Importantly, in a Brief Access Taste Task, calcium responses for D1 and D2 exhibit much more heterogeneity than during a freely licking task. Specifically, D1 and D2 neurons form distinct ensembles: some ramp up in anticipation of the first lick, some respond at the end of the taste-access period, and some categorize sucrose concentrations as low or high. Collectively, NAcLat D1 and D2 neurons are organized in ensembles that adapt to the behavioral context to monitor task-relevant events and sucrose concentrations.