Determination of the Role of Synapse Associated Protein 97 (SAP97) in the Normal and Parkinsonian Striatum By

Parkinson’s disease (PD) is a debilitating movement disorder associated with the death of dopaminergic nigrostriatal neurons. In addition to dopamine deficiency, abnormalities in glutamate and other receptors at striatal synapses have been reported. Synapse associated protein 97 (SAP97) is involved in regulation of glutamate receptor function. In the striatum of unilaterally-lesioned 6-OHDA rat model of PD, SAP97 levels are decreased in post synaptic density fraction, as well as in the whole striatum. I hypothesize that changes in striatal levels and subcellular distribution of SAP97 are responsible for abnormal neurotransmission in striatume and the motor symptoms of PD. GFP-tagged wild type SAP97 and SAP97 mutants were over-expressed in the striatum of 6-OHDAlesioned rat model of PD. A single 6.5 mg/kg dose of L-DOPA eliminated parkinsonism in 6-OHDA-lesioned rats over-expressing SAP97-GFP, whereas, three 6.5 mg/kg doses of L-DOPA negated parkinsonism in 6-OHDA-lesioned rats over-expressing SAP97-GFP and SAP97∆1-65-GFP. The over-expression of SAP97∆1-65-GFP enhanced parkinsonism in 6-OHDA-lesioned rats and blocked the antiparkinsonian effect of L-