Date of Award

Summer 5-22-2016

Document Type

Undergraduate Honors Thesis

Degree Name

Bachelor of Arts in Behavioral Neuroscience

Department

Psychological Sciences

Advisor

Peter W Vanderklish

Abstract

Fragile X Syndrome--the most common inherited form of intellectual disability--is characterized by low IQ, impaired social interaction, hyperactivity and impulsivity, and abnormal physical traits including an elongated face and protruding ears. Nearly half of all children with Fragile X also meet diagnostic criteria for autism spectrum disorder. Fragile X is caused by a trinucleotide repeat expansion on the X chromosome, leading to silencing of the Fragile X mental retardation gene (FMR1) and thus lack of expression of Fragile X mental retardation protein (FMRP). As a key translational suppressor, FMRP is crucial for normal neural development and synaptic function. The current study investigates a group of synaptic proteins implicated in both autism and Fragile X that may be over-expressed in Fragile X glutamatergic synapses. Additionally, previous research has shown that these proteins likely participate in a common signaling cascade that functions abnormally in Fragile X. Using the FRM1 knockout (KO) mouse, the study validated that this set of proteins was up-regulated in KO mice compared to wild-type (WT) and discovered that the downstream signaling molecules in this complex of proteins are modulated by the same neurotransmitter receptor systems that lead to exaggerated long-term depression in Fragile X. Current research on this project involves conduct functional assays of the final product of this protein complex (ADP-ribosylation factor 6) utilizing synaptoneurosomes.

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