Assesment of differential microglial reactivity in the VPA rat model of autism

TRAETTA MARIANELA; CODAGNONE MARTIN; UCCELLI NONTHUE; MALLEVILLE CORPA MARÍA JOSÉ; ZÁRATE SANDRA; REINÉS ANALÍA

Simposio; The role of Glia in Health and Disease of the Nervous System: Clinical and Basic Science Walking Together; 2017

Autism spectrum disorders (ASD) are characterized by impairments in social interaction and repetitive-stereotyped behaviours. A well validated ASD animal model, based on prenatal exposure to valproic acid (VPA), mimics the main behavioural and neuroanatomical alterations found in these disorders. We previously reported anincrease in synaptic protein synaptophysin (SYN) accompanied with reactive gliosis in the medial prefrontal cortex (mPFC) of juvenile VPA rats. The aim of this study was to characterizein vitrothe morphological and functional profile of microgliafrom VPA animals.Microglia cells were isolated and purified from P3-P5 male rat pups after in utero (E10.5) VPA (500 mg/kg) or saline exposure.Tomato lectin labelling was assessed to study microglia morphology either under basal condition or LPS stimulus. Besides, morphological characterization by IBA-1 immunostaining was evaluated after incubation with corticalsynaptosomes. While microglia from VPA animals showed an increasedcircularity index compared to control ones;either control or VPA group showed conserved response to LPS inflammatory stimulus by further increasingcellular circularity. When exposed to synaptosomes, only the microglia from control animals were capable of activation. Our resultsindicate ahigher basal microglial reactivity and suggest a distinctive pattern of activation in the VPA group.Our finding highlights the importance ofneuro-glia interaction in the pathogenesis of ASD.