A Preliminary Study of Mild Heat Stress on Inflammasome Activation in Murine Macrophages.

Inflammation and mitochondrial-dependent oxidative stress are interrelated processes implicated in multiple neuroinflammatory disorders, including Alzheimer's disease (AD) and depression. Exposure to elevated temperature (hyperthermia) is proposed as a non-pharmacological, anti-inflammatory treatment for these disorders; however, the underlying mechanisms are not fully understood. Here we asked if the inflammasome, a protein complex essential for orchestrating the inflammatory response and linked to mitochondrial stress, might be modulated by elevated temperatures. To test this, in preliminary studies, immortalized bone-marrow-derived murine macrophages (iBMM) were primed with inflammatory stimuli, exposed to a range of temperatures (37-41.5 °C), and examined for markers of inflammasome and mitochondrial activity. We found that exposure to mild heat stress (39 °C for 15 min) rapidly inhibited iBMM inflammasome activity. Furthermore, heat exposure led to decreased ASC speck formation and increased numbers of polarized mitochondria. These results suggest that mild hyperthermia inhibits inflammasome activity in the iBMM, limiting potentially harmful inflammation and mitigating mitochondrial stress. Our findings suggest an additional potential mechanism by which hyperthermia may exert its beneficial effects on inflammatory diseases.

Neurocognitive Mechanisms of Social Inferences in Typical and Autistic Adolescents.

BACKGROUND: Many of our efforts in social interactions are dedicated to learning about others. Adolescents with autism have core deficits in social learning, but a mechanistic understanding of these deficits and how they relate to neural development is lacking. The present study aimed to specify how adolescents with and without autism represent and acquire social knowledge and how these processes are implemented in neural activity. METHODS: Typically developing adolescents (n = 26) and adolescents with autism spectrum disorder (ASD) (n = 20) rated in the magnetic resonance scanner how much 3 peers liked a variety of items and received trial-by-trial feedback about the peers' actual preference ratings. In a separate study, we established the preferences of a new sample of adolescents (N = 99), used to examine population preference structures. Using computational models, we tested whether participants in the magnetic resonance study relied on preference structures during learning and how model predictions were implemented in brain activity. RESULTS: Typically developing adolescents relied on average population preferences and prediction error updating. Importantly, prediction error updating was scaled by the similarity between items. In contrast, preferences of adolescents with ASD were best described by a No-Learning model that relied only on the participant's own preferences for each item. Model predictions were encoded in neural activity. Typically developing adolescents encoded prediction errors in the putamen, and adolescents with ASD showed greater encoding of own preferences in the angular gyrus. CONCLUSIONS: We specified how adolescents represent and update social knowledge during learning. Our findings indicate that adolescents with ASD rely only on their own preferences when making social inferences.