Early behavioral and physiological alterations in a mouse model of autism

NADIA KAZLAUSKAS; LUCIANA LUCCHINA; MARCOS CAMPOLONGO; LUIS BOERO; MARÍA EUGENIA GOMEZ CASATI; AMAICHA DEPINO

Congreso; XXX Annual Meeting of Argentinean Society for Neuroscience; 2015

Autism is a neurodevelopmental disorder characterized by impaired sociability andstereotypic behaviors. Individuals also have auditory symptoms, i.e. hypersensitivity toloudness of sound with abnormal behavioral reactions to environmental sounds. Wehypothesized that there is a developmental critical window in which maturation andconsolidation of the neural systems responsible for these symptoms typically occur.The administration of VPA at GD 12.5 results in autism-related behaviors in adulthood. Theaim of this work is to characterize early alterations in this model. We found a delay in theapparition of the righting reflex and in the acoustic startle response. To furthercharacterize this last deficit, we measured the auditory brainstem response (ABRs), whichreflect synchronized discharges from neurons along the auditory pathway and found anelevated threshold profile at P14-P16 and P21-P23 in VPA mice. This shows that thematuration delay observed leads to a lasting alteration in hearing function.We observed other alterations in the brain at P21: VPA animals show higher GFAP+ densityand activated microglia in the hippocampus, but fewer activated microglial cells in thecerebellum.In summary, we found that mice prenatally exposed to VPA show altered physiologicalresponses at the third postnatal week. Current experiments are testing whether this periodis a critical period for autism related behaviors.