McNair/Gateway Scholars Program USC

Brandyn Castro

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Major and Classification

Neuroscience/Business Administration, May 2010

Faculty Mentor

  • Michael Jakowec, Ph.D.

Department

  • Neurology

McNair Project

Molecular Differences in Striatum of Fischer 344 Rats, A New Animal Model of Autism

Abstract
The purpose of this study is to examine the neurological differences in protein levels and concentrations in Autism. The following are two aspects that will be introduced to the field: (1) the utilization of the Fischer 344 rat as an animal model of Autism and (2) the evaluation of the protein tyrosine hyroxylase (TH). TH is the enzyme that catalyzes the conformation of L-tyrosine into L-DOPA, the precursor to dopamine. Dopamine is a vital neurotransmitter for normal function within the brain and serves as a precursor for norenephrine (noradrenaline) and epinephrine (adrenaline). Dopamine is produced in the striatum which leads us to perform immunocytochemistry and western blots to determine that there are lower levels of TH in the striatal area of Fischer 344 as compared to Sprague Dawley controls. This could lead to a variety of outcomes such as: lower levels of dopamine or higher levels of TH phosphorylation in the striatum in Autism. Future studies comparing additional proteins will give more insight into the proper analysis of these findings. Such proteins that merit further study include: dopamine transporter (DAT), glutamate receptor-1 (GluR1), glutamate receptor-2 (GluR2), metabotropic glutamate receptor-1 (mGluR1), and metabotropic glutamate receptor-5 (mGluR5). DAT is a protein spanning the membrane that binds dopamine and transports it from the intersynaptic space into the post-synaptic neuron. The glutamatergic system is necessary for normal brain function and has been compromised in other neurological disorders such as Parkinson's Disease. This study (and future studies that stem from it) will lead to better insight as to the mechanisms behind the Autistic disorder and possibly lead to a cure.