Molecular Differences in the Fischer 344 Rat, A New Animal Model of Autism

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 LDOPA, 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 substantia nigra which sends projections to the striatum. Immunocytochemistry (ICC) was performed at the level of the midstriatum, prefrontal cortex, and caudal end of the temporal lobe. It was determined that there are lower levels of TH in the striatal area of Fischer 344 as compared to Sprague Dawley controls. This shows that there are lower levels of dopamine in the striatum in the Fischer 344 which correspond with the dysfunction in the dopaminergic system seen in Autism. No difference was seen in the TH levels of the prefrontal cortex and amygdala. Ongoing studies are further analyzing the Fischer 344 rat as an animal model of Autism. Western blot analysis will be performed with the hope of validating these present findings. ICC and western blots will be assess dopamine transporter to hopefully confirm that the TH levels do in fact correlate with dopamine levels. The glutamatergic system will also be examined in the Fischer 344 because dysfunction in this pathway has been seen in Autism. In conclusion, the Fischer 344 strain may be a useful animal model for identifying neurobiological pathways involved in Autism-related phenotypes. INTRODUCTION Autism is a condition that was first described over 50 years ago. Later in 1998, Rapin et al. defined Autism as a developmental disorder that can be characterized by behavioral symptoms across three general areas: social reciprocity, communication, and restricted and repetitive interests and