Glutamate Kinetics in a Middle Aged Mouse Model of Parkinson's Disease

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Quattlebaum, Ariana
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GDNF, a known growth factor, is important for maintaining the health of dopamine (DA) neurons. Parkinson’s (PD) patients have a greatly decreased number of DA neurons in the substantia nigra (SN) while existing nigral neurons have a down regulation of GDNF. Animal models with partial GDNF reduction show an accelerated decline in the SN DA system and motor function similar to PD. Increased glutamate release in the subthalamic nucleus also occurs in PD patients. The purpose of the current study is to help determine the role of glutamate in a GDNF+/- model of PD. Potassium-stimulated glutamate release and uptake in the SN was assessed in anesthetized 12-month-old wild type (WT) and GDNF+/- mice (partial gene knockouts with decreased GDNF levels) by electrochemical detection. After this procedure, western blots helped determine how much glutamate transporter was in each tissue sample, and tissue staining allowed determination of phospho-mTOR levels in the SN (a measure of cellular stress). Initial data indicates high levels of glutamate are released in GDNF+/- tissue, as well as low levels of the transporter GLT-1. Staining results showed an upregulation of phospho-mTOR expression in the SN pars reticulata (SNpr). These results support the idea that glutamate excitotoxicity may play a role in cell death of PD patients, and that cell death leads to additional stress on nearby cells, potentially as an injury response.
neuroscience, nigrostriatal pathway, Parkinson's Disease, glutamate, dopamine, GDNF, glial cell-derived neurotrophic factor, substantia nigra, phosphorylated mTOR