Date of Award

Spring 2014

Degree Name

Bachelor of Science

Major

Neuroscience

First Advisor

Susan Masino

Second Advisor

David Ruskin

Abstract

BACKGROUND: A ketogenic diet (KD), which has restricted carbohydrates, sufficient protein, and a very high fat content, causes the body to switch from a glucose-based metabolism to a ketone-based metabolism. The KD has been effective at reducing seizures in epileptic patients. Autism is comorbid with epilepsy and characterized by restricted and repetitive behaviors, low sociability, and deficits in communication. A strict version of the long-chain triglyceride (LCT) KD has been effective at reducing autistic symptoms in BTBR T+tf/J, an autistic model of mice. However, a more moderate and clinically relevant version of the LCT KD has been shown to be ineffective in this model. Recent studies suggest that a KD derived primarily from medium chain triglycerides (MCTs) will effectively reduce the severity of autistic symptoms. A MCT KD has been shown to cause an increase in ketone bodies, acetyl-CoA, and ATP similar to a LCT KD. However, MCTs are hydrolyzed faster than LCTs and provide more kilocalories per gram of fat, allowing it to maintain clinical relevancy. Furthermore, only odd-numbered MCTs are anaplerotic substances, meaning that the metabolites of the Krebs cycle are refilled. Thus, the goal of the study was to determine a) if either even- or odd-numbered MCTs result in a beneficial alleviation of autistic symptoms in mice and b) the role of anaplerosis in modifying behavior and establishing ketosis.

METHODS: BTBR T+tf/J mice were given one of the following metabolic treatments for three weeks: pellet chow (control), pellet chow balanced with 17% cellulose, 17% heptanoic acid KD (odd-numbered MCTs), and 17% octanoic acid (even-numbered MCTs). A battery of behavioral tests was given in order to quantify the core symptoms of autism, including deficits in sociability, communication, and motor control as well as self-directed repetitive behaviors. Furthermore, glucose and ketone blood analysis were conducted in order to elucidate the mechanisms of the diet.

RESULTS: The mice in the pellet and cellulose control groups did not clearly exhibit autistic behaviors as expected, primarily in the three-chamber test for sociability and self-directed repetitive behavior. However, the heptanoic and octanoic treatment groups spent significantly more time engaged in frontal contact than the cellulose control.

CONCLUSION: The results of the current study are conflicting and inconclusive. The effects of even- and odd-numbered MCT KDs should be investigated and expanded further in order to understand the impact of this metabolic treatment on alleviating autistic symptoms.

Comments

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

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