Modelling an autism risk factor in rats. The impact of perinatal immune challenges on gastrointestinal inflammation and integrity

Abstract

A growing subset of Autism Spectrum Disorder (ASD) sufferers present with comorbid gastrointestinal (GI) abnormalities. Research suggests these abnormalities may be involved in the aetiology, pathogenesis and pathophysiology of ASD, however, the biological pathways involved are unknown. As human prenatal infection has been associated with an increased risk of ASD in offspring, animal models of maternal immune activation (MIA) have provided researchers a translational tool to investigate the biological abnormalities underlying neurodevelopmental disorders such as ASD. The current study aimed to determine if MIA would produce ASD-like GI inflammation and integrity disruptions. Pregnant rats were exposed to Poly-I:C (MIA) at gestational day (GD) 10 and 19. A segment of distal large intestine was extracted from offspring on postnatal days (P) 7, 21 and 84. Tissue was examined for expression of tight junction protein and proinflammatory cytokine mRNA. Adult offspring were examined for anxiety-related behaviour. P7 MIA offspring exhibited alterations in tight junction proteins as well as proinflammatory immune markers. P21 and P84 offspring exhibited subtle alterations in tight junction proteins however no alterations in inflammatory markers were observed. Adult MIA offspring exhibited increased anxiety-related behaviour. MIA alters expression of pro-inflammatory cytokines and GI tight junction proteins during early development, with alterations diminishing throughout adulthood. Early changes in GI integrity may impact the trajectory of brain development leading to ASD.