Date of Award

Spring 2015

Degree Name

Bachelor of Science

Major

Neuroscience

First Advisor

David Ruskin, PhD

Abstract

Autism spectrum disorder (ASD) is a neurological disorder characterized by decreased sociability, deficits in communication, and restricted and repetitive behaviors. The ketogenic diet (KD), a high-fat, low-carbohydrate, and moderate-protein diet has been shown to improve these three behavioral symptoms in the BTBR mouse model of autism. However, further research is required to strengthen the body of knowledge surrounding the potential of KD as diet therapy for autism. Epidemiological observations have shown that maternal immune activation (MIA) during pregnancy increases the risk of autism in offspring. Based on these observations, the polyinosinic:polycytidylic acid (poly(IC)) mouse model was developed as an animal model to study autism. Poly(IC) is a synthetic analog of double stranded RNA and acts as a viral mimic. It is injected into a pregnant dam, activating an immune response without causing an infection. The offspring of this protocol are the poly(IC) MIA mouse model. They have been shown to have the autistic symptoms of deficits in sociability and communication as well as increased repetitive behaviors. In this study, pregnant dams were injected with poly(IC) or the saline vehicle during the late first trimester. The offspring were separated into control and test groups. At 5 weeks of age, the test group was placed on a 6:1 fat:(carbohydrates + protein) KD while the control groups remained on standard chow. After three weeks on the diet, we assessed sociability, repetitive behavior, and communication. Our results showed that KD reversed increased self-grooming in poly(IC) mice. Results did not indicate autistic-like behavior in our poly(IC) mice for social contact, sociability, grooming during the 3-chamber test, or repetitive behavior in the marble-burying test. However, KD increased social contact in poly(IC) mice. It also increased sociability and decreased 3-chamber grooming in poly(IC) males. Poly(IC) mice did not have a deficit in the social transmission of food preference task, a previously unused assessment of the poly(IC) mouse model. While our study did not succeed in replicating several autistic behaviors in the poly(IC) mouse model, KD had influence on behavior in multiple measures, increasing sociability and decreasing grooming. This suggests that KD may be an effective diet therapy for autism.

Comments

Senior thesis completed at Trinity College for the degree of Bachelor of Science in Neuroscience.

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