In search of the role of microglia in the sex-dependent behavioral profile in autism spectrum disorder

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

Congreso; Reunión Conjunta SAIC, SAI, AAFE, NANOMED; 2021

Autism spectrum disorder (ASD) is characterized by impairments in social interaction and repetitive-stereotyped behaviors. The incidence is higher in boys, and girls present different type and grade of symptoms. As microglia show sex-dependent features and reactive microgliosis has been reported both in patients and animal models of ASD, they are proposed to play a key role in ASD sex-differences. The experimental model of ASD by prenatal exposure to valproic acid (VPA) mimics the main behavioral and neuroanatomical alterations found in patients. The aim of this work was to study microglia features in male and female VPA rats in the prefrontal cortex (PFC) and the hippocampus (HP). Microglia were immunostained for Iba1 on tissue slices of juvenile control and VPA rats of both sexes. The PFC of both male and female VPA rats showed microgliosis characterized by a higher proportion of iba1 (+) unramified cells. However, in the HP, microgliosis was only evident in female VPA rats. To evaluate microglia reactivity and response to different stimuli we performed microglia primary cultures from control and VPA neonates. Microglia were immunolabeled for Iba1 to study morphology under basal conditions and after exposure either to a pro-inflammatory (lipopolysaccharide) or a phagocytic (synaptosomes) stimulus. While cortical microglia from male VPA animals showed a pro-inflammatory profile and an intrinsic resistance to phagocytic stimuli, hippocampal microglia from male VPA animals matched microglia from controls under basal condition and showed a preserved response to pro-inflammatory and phagocytic stimuli. In the case of microglia isolated from females, both cortical and hippocampal microglia from VPA rats evidenced morphological changes under basal conditions but both were able to respond to pro-inflammatory and phagocytic stimuli. To sum up, microglia from male and female VPA rats show sex-dependent changes which may contribute to sex-differences in ASD.