Meshul Special

Our laboratory is mainly involved in investigating electron microscopic/immunocytochemical changes in synapses within the brain following various drug treatment procedures or lesions of the nigrostriatal pathway, as a model for Parkinson’s disease (PD), and correlating these findings with functional/protein changes using in vivo microdialysis/westerns and motor behaviors in mice. Using a new progressive mouse model of PD developed in my lab, by administering increased doses of the toxin, MPTP, we have found that exposure of mice to a socially enriched environment can, after the initiation of the loss of dopamine, slow down or block the neurochemical and motor behavioral deficits due to continued treatment with MPTP. We are currently investigating 1.) the therapeutic affects of exercise in this same progressive MPTP model of PD in both young and aged mice, 2.) the effect of MPTP in a double floxed line of mice (lox-P-Vgat; lox-P-Vglut2) in which either the motor cortex is activated or the subthalamic nucleus is inactivated by infusion of AAV-cre. Either treatment results in neuroprotection from dopamine loss in the striatum and substantia nigira, and 3.) the effect of a flavinoid derivative, which specifically activates the brain derived neurotrophic factor receptor, TrkB, on blocking the further loss of dopamine during continued MPTP treatment.