ASSESSMENT OF DIFFERENTIAL MICROGLIAL REACTIVITY IN THE VPA RAT MODEL OF AUTISM

TRAETTA ME; MALLEVILLE CORPA MJ; UCCELLI NA; REINÉS A; CODAGNONE M; ZÁRATE S

Buenos Aires

Conferencia; The role of glia in health and disease of the nervous system: Clinic and basic research walking together; 2017

Sociedad Argentina de Investigación en Neurociencias (SAN)

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 an increase 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 characterize in vitro the morphological and functional profile of microglia from 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 cortical synaptosomes. While microglia from VPA animals showed an increased circularity index compared to control ones; either control or VPA group showed conserved response to LPS inflammatory stimulus by further increasing cellular circularity. When exposed to synaptosomes, only the microglia from control animals were capable of activation. Our results indicate a higher basal microglial reactivity and suggest a distinctive pattern of activation in the VPA group. Our finding highlights the importance of neuro-glia interaction in the pathogenesis of ASD.