The role of lipids in neuronal plasticity—a link to autism spectrum disorders

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by deficits in social communication and by restricted and repetitive behaviours. ASD impacts 1 in 66 children and is four times more likely to appear in males. Recent research provides evidence for the link between abnormal lipid (or fats) signalling in the brain and ASD. Lipids are critical for healthy brain development, including synaptic plasticity. Synaptic (or neuronal) plasticity involves the dynamic changes of connections formed in the brain between neurons (or brain cells). Previous studies demonstrated abnormal levels of prostaglandin E2 (PGE2), the major bioactive lipid in the brain, which can be influenced in pregnancy by environmental factors such as air pollution, aspirin, or inflammation and lead to ASD. Our lab investigates how molecular mechanisms of abnormal prenatal levels of PGE2 affect brain pathology and lead to ASD. The goal of this study is to determine if changes in the level of PGE2 can influence neuronal plasticity. We tested this in vivo in the mouse cerebellum through analysis of neuronal morphology and in vitro detection of nitric oxide (NO) production, an indicator of synaptic plasticity. We used Golgi-cox staining, confocal microscopy, and open-source software to analyze stage and sex differences of aspects of neuronal morphology. Additionally, the influence of PGE2 in regulating nitric oxide production in differentiating neurons was investigated, using time-lapse fluorescence microscopy. Our novel findings show that healthy brain development is influenced by sex and neurodevelopmental stage. Furthermore, we provide evidence that exposure to PGE2 leads to increased production of nitric oxide in differentiating neurons in vitro. Our study provides insight into the importance of PGE2 signalling in neuronal plasticity; abnormal levels may influence brain development and can lead to neurodevelopmental disorders such as ASD.