WIP 77 - Dissecting how maternal high fat diet disrupts somatosensory circuit development

Publication Number: WIP 77.7650

Clare Howard, Boston Children's Hospital, Boston, MA, United States; Emily R. Temple, Harvard Medical School, Stoughton, MA, United States; Lauren L.. Orefice, Massachusetts General Hospital / Harvard Medical School, Boston, MA, United States

Background: Epidemiological studies have shown a link between inflammatory states in pregnancy (whether caused by maternal obesity, infection, or exposure to pollutants) and neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). Features of this broad array of neurodevelopmental disorders are diverse, but many share a dysregulation of touch processing, which is often correlated with worse core symptoms of disease. Genetic mouse models have suggested a significant contribution of tactile hypersensitivity to the pathophysiology of a variety of neurodevelopmental disorders. However, little is known about how the in utero environment can disrupt the development of tactile circuitry.

Objective: Touch stimuli from the body skin are detected by a wide variety of specialized somatosensory neurons of the dorsal root ganglia (DRG) which then relay this information for further processing in the spinal cord and brain. This project will investigate the mechanisms through which maternal high fat diet may disrupt the development and function of somatosensory circuits in mice. Our central hypothesis is that maternal high fat diet disrupts DRG to spinal cord circuit development in neonatal mice, resulting in long term dysfunction and persistent tactile hypersensitivity in offspring.

Design/Methods: Using a well-characterized mouse model of maternal high fat diet exposure, we will assess offspring for tactile hypersensitivity using a validated battery of behavioral assays. Our preliminary data suggest that maternal high fat diet-exposed mice exhibit tactile hypersensitivity in adulthood. We will also assess whether maternal high fat diet disrupts DRG and/or spinal cord neuron responses to touch using in vivo electrophysiology approaches.