Morphological Correlates of Behavioral Variation in Autism Spectrum Disorder Groups in A Maternal Immune Activation Model.

Abstract

Clinical heterogeneity is one of the biggest challenges for researchers studying underlying neurobiological mechanisms in Autism Spectrum Disorder (ASD). We aimed to use polyinosinic-polycytidylic acid [Poly (I:C)] induced maternal immune activation mice model to investigate the behavioral variation and the role of brain circuits related to symptom clusters in ASD. For this purpose, behavioral tests were applied to offsprings and regional thickness was measured from histological brain sections in medial prefrontal cortex, hippocampus and striatum. Pups of intraperitoneal Poly (I:C)-applied mothers (n: 14) and phosphate buffered saline-applied mothers (n: 6) were used for this study. We used three chamber socialization test and social memory test to evaluate social behavior deficit in mice. Marble burying test was used for assessing stereotypic behavior and new object recognition test for learning and cognitive flexibility. Three subgroups (n: 4 for each) were determined according to behavioral test parameters. Regional thickness was measured in medial prefrontal cortex, hippocampus and striatum and compared between subgroups. We detected that the behavioral differences were distributed in a spectrum as expected in the clinic and also detected increased hippocampus thickness in the stereotypic behavior dominant Poly (I:C) subgroup. Poly (I:C) induced maternal immune activation model creates the behavioral variation and cortical development differences that are seen in relation with symptom groups in ASD.