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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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.
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Mild cognitive impairment occurs in rats during the early remodeling phase of myocardial infarction.
Cognitive impairment is a common health problem among people with heart failure (HF). Increases in oxidative stress, brain inflammation, and microglial hyperactivity have been reported in preclinical models of myocardial infarction (MI)-induced HF. We tested the hypothesis that oxidative stress, brain inflammation, mitochondrial dysfunction, and cell death participate in cognitive impairment in the early remodeling phase of MI. ⋯ However, brain inflammation and AD proteins did not change. In conclusion, during the early remodeling phase of MI, a high level of oxidative stress appears to be a major contributor of cellular damage which is associated with mild cognitive impairment. However, the severity of MI, as evidenced by the %LVEF, was not associated with the degree of cognitive impairment.
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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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Characterizing the functional involvement of specific brain regions has long been a central challenge in cognitive neuroscience. Functional magnetic resonance imaging (fMRI) techniques have offered solutions for mapping functional neural networks. The complex nature of structure-function correspondence makes an elaborate task design difficult to fully capture higher-order cognitive function. ⋯ Just like looking up a "coordinate-based cognition dictionary", researchers can receive a plethora of related tb-fMRI activation information characterized by cognitive domains, specific cognitive functions, cognitive task paradigms, and related publications. Surprisingly, we found that only less than 1% of brain-behavior association or between-group comparison studies have utilized this dictionary approach. We encourage the community to further engage with the existing databases for specific and comprehensive interpretation of neuroimaging as well as guidance of future experimental tb-fMRI design.