CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model.

Microglia are central to pathogenesis in many neurological conditions. Drugs targeting colony-stimulating factor-1 receptor (CSF1R) to block microglial proliferation in preclinical disease models have shown mixed outcomes, thus the therapeutic potential of this approach remains unclear. Here, we show that CSF1R inhibitors given by multiple dosing paradigms in the Tg2541 tauopathy mouse model cause a sex-independent reduction in pathogenic tau and reversion of non-microglial gene expression patterns toward a normal wild type signature. Despite greater drug exposure in male mice, only female mice have functional rescue and extended survival. A dose-dependent upregulation of immediate early genes and neurotransmitter dysregulation are observed in the brains of male mice only, indicating that excitotoxicity may preclude functional benefits. Drug-resilient microglia in male mice exhibit morphological and gene expression patterns consistent with increased neuroinflammatory signaling, suggesting a mechanistic basis for sex-specific excitotoxicity. Complete microglial ablation is neither required nor desirable for neuroprotection and therapeutics targeting microglia must consider sex-dependent effects.

Dynamic Eye Tracking as a Predictor and Outcome Measure of Social Skills Intervention in Adolescents and Adults with Autism Spectrum Disorder.

To evaluate an eye tracking task as a predictor and outcome measure of treatment response for autism spectrum disorder (ASD) social skills interventions, adolescents and young adults with ASD completed the eye tracking task before, immediately after, and two months after completing Social Cognition and Interaction Training for Autism (SCIT-A). The study compared SCIT-A participants (n = 20) to participants with ASD who received treatment as usual (TAU; n = 21). Overall, increased visual attention to faces and background objects and decreased attention to hands playing with toys at baseline were associated with improved social functioning immediately following intervention, suggesting this eye tracking task may reliably predict ASD social intervention outcomes.