S-050
Cerebellar Involvement in Sociability: Focus on Inflammatory Mechanisms
Veronica Murta1,2, Cecilia Mariel Zappala1, Florencia Alejandra Kloster1, Amaicha Depino1,3
  1. Laboratory of Neurobiology of Autism and Social Behaviors (IFIByNE - UBA, CONICET)
  2. Department of of Physiology, Molecular Biology and Cell Biology, Faculty of Exact and Natural Sciences, UBA
  3. Department of Biodiversity and Experimental Biology, Faculty of Exact and Natural Sciences, UBA
Presenting Author:
Veronica Murta
vmurta.fmed@gmail.com
Sociability, defined as the tendency to interact with conspecifics, is frequently disrupted in psychiatric and neurodevelopmental disorders, including autism spectrum disorder (ASD). Although the cerebellum has been traditionally associated with motor control, increasing evidence points to its involvement in cognition, affective regulation, and the neuropathology of ASD. Here, we examined the contribution of cerebellar lobule VI/VII to sociability, with a focus on neuroinflammatory mechanisms. Using the prenatal valproic acid (VPA) mouse model, we confirmed that male offspring exhibit reduced sociability and early postnatal alterations in Purkinje cell density, although these structural differences were not observed in adulthood. Furthermore, induction of neuroinflammation in lobule VI/VII of adult males led to pronounced social deficits, which were completely prevented by systemic dexamethasone and only partially prevented by ibuprofen. Consistent with these behavioral results, microglial activation was reduced in dexamethasone-treated animals. Together, these findings implicate NFκB-dependent microglial activation in cerebellar regulation of social behavior and highlight pharmacological modulation of neuroinflammation as a potential therapeutic avenue for ASD-related sociability impairments.