Maternal exposure to prostaglandin e2 results in abnormal dendritic morphology in the cerebellum and related motor behaviour in mouse offspring

Abstract

AbstractThe lipid signalling molecule prostaglandin E2 (PGE2) is important in healthy brain development. Abnormal PGE2 levels during prenatal development, which can be influenced by genetic causes and exposure to various environmental risk factors, have been linked to increased prevalence of Autism Spectrum Disorders (ASDs). Growing research in animal models aims to provide evidence for the mechanisms by which increased or reduced PGE2 levels influence brain development. In this study, we show that maternal exposure to PGE2 in mice at gestational day 11 (G11) results in molecular changes within the cerebellum and associated behaviours in offspring. We observed a decrease in cerebellar cell density originating at G11 (in males and females) and at G16 (in females only). In Golgi-COX-stained cerebellar slices from PGE2-exposed offspring at the postnatal day 30 (PN30), we found an increase in dendritic arborization, the odds of observing dendritic loops, dendritic spine density, and the odds of observing mature (mushroom-shaped) spines. We also observed a decrease in the expression level of the cytoskeletal protein β-actin, the actin associated protein spinophilin, and the cell adhesion protein N-Cadherin. In addition, we found that specifically PGE2-exposed male offspring exhibited abnormal cerebellar related motor function. This study adds further evidence that changes in the PGE2 levels during critical times may impact the developing brain differently in males and females. These findings also emphasize the importance of examining sex differences in research relevant to neurodevelopmental disorders.