Dopamine is a neurotransmitter in the brain that is involved with a variety of functions, including motor control, sensory-motor integration, motivation and drive, reward mechanisms, and endocrine control. Knowledge of how dopamine levels are regulated and controlled is important for understanding these functions. Brain dopamine systems have also been linked to various diseases, such as Parkinson's disease, and are a primary target for many drugs of abuse, particularly the psychomotor stimulants such as cocaine and methamphetamine. The focus of my research is on characterizing the mechanisms involved with the regulation and modulation of dopamine release and reuptake in the brain in normal animals, in aged animals, and in animal models of neurodegenerative diseases.
Recent studies have involved examination of potential neuroprotective agents in Parkinson’s disease models and in rodent models of methamphetamine neurotoxicity, and the development and characterization of novel models of Parkinson's disease. Rats treated with dopaminergic toxins are similar, in many respects, to humans with Parkinson's disease. We are presently characterizing changes in dopamine function in several animal models and are evaluating the ability of neurotrophic factors to promote behavioral recovery and to return dopaminergic activity to more normal levels. In other projects we are examining the neuroprotective and restorative effects of calcitriol, the active metabolite of vitamin D, in models of dopamine neuron degeneration, and we are finding promising results both in animal models of Parkinson's disease and in models of methamphetamine toxicity. The results of these studies should increase our understanding of changes in brain dopamine systems in Parkinson's disease and drug abuse and could lead to improved treatment strategies for persons with these diseases.
Fuqua, J.L., Littrell, O.M., Lundblad, M., Turchan-Cholewo, J., Abelmoti, L.G., Galperin, E. Bradley, L.H., Cass, W.A., Gash, D.M. and Gerhardt, G.A. (2014) Dynamic Changes in Dopamine Neuron Function after DNSP-11 Treatment: Effects in vivo and Increased ERK 1/2 Phosphorylation in vitro. Peptides 54: 1-8.
Cass, W.A., Peters, L.E., Fletcher, A.M. and Yurek, D.M. (2012) Evoked dopamine overflow is augmented in the striatum of calcitriol treated rats. Neurochem. International 60: 186-191.
Cass, W.A. and Peters, L.E. (2010) Neurturin protects against 6-hydroxydopamine-induced reductions in evoked dopamine overflow in rat striatum. Neurochem. International 57: 540-546.
Liu, M., Choi, D.Y., Hunter, R.L., Pandya, J.D., Cass, W.A., Sullivan, P.G., Kim, H.-C., Gash, D.M. and Bing, G. (2010) Trichloroethylene Induces Dopaminergic Neurodegeneration in Fisher 344 Rats. J. Neurochem. 112: 773-783.
Gash, D.M., Rutland, K., Hudson, N.L., Sullivan, P.G., Bing, G., Cass, W.A., Pandya, J.D., Liu, M., Choi, D.-Y., Hunter, R.L., Gerhardt, G.A., Smith, C.D., Slevin, J.T. and Prince, T.S. (2008) Trichloroethylene: parkinsonism and complex 1 mitochondrial neurotoxicity. Annals of Neurology 63: 184-192.
Theodore, S., Cass, W.A., Nath, A. and Maragos, W.F. (2007) Progress in understanding basal ganglia dysfunction as a common target for methamphetamine abuse and HIV-1 neurodegeneration. Curr. HIV Res. 5: 301-313.
Smith. M.P. and Cass, W.A. (2007) Oxidative stress and dopamine depletion in an intrastriatal 6-hydroxydopamine model of Parkinson’s disease. Neuroscience 144: 1057-1066.
Smith. M.P. and Cass, W.A. (2007) GDNF reduces oxidative stress in a 6-hydroxydopamine model of Parkinson’s disease. Neurosci. Lett. 412: 259-263.
Cass, W.A., Grondin, R., Andersen, A.H., Zhang, Z., Hardy, P.A., Hussey-Andersen, L.K., Rayens, W.S., Gerhardt, G.A. and Gash, D.M. (2007) Iron accumulation in the striatum predicts aging-related decline in motor function in rhesus monkeys. Neurobiol. Aging 28: 258-271.
Smith, M.P., Fletcher-Turner, A., Yurek, D.M. and Cass, W.A. (2006) Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem. Res. 31: 533-539.
Cass, W.A., Peters, L.E. and Smith, M.P. (2005) Reductions in spontaneous locomotor activity in aged male, but not female, rats in a model of early Parkinson’s disease. Brain Res. 1034: 153-161.
Cass, W.A., Harned, M.E., Peters, L.E., Nath, A. and Maragos, W.F. (2003) HIV-1 protein Tat potentiation of methamphetamine-induced decreases in evoked overflow of dopamine in the striatum of the rat. Brain Res. 984: 133-142.
Fox, C.M., Gash, D.M., Smoot, M.K. and Cass, W.A. (2001) Neuroprotective effects of GDNF against 6-OHDA in young and aged rats. Brain Res. 896: 56-63.
Cass, W.A. and Manning, M.W. (1999) Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine. J. Neurosci. 19: 7653-7660.
Cass, W.A. and Manning, M.W. (1999) GDNF protection against 6-OHDA-induced reductions in potassium-evoked overflow of striatal dopamine. J. Neurosci. 19: 1416-1423.
Cass, W.A. (1996) GDNF selectively protects dopamine neurons over serotonin neurons against the neurotoxic effects of methamphetamine. J. Neurosci. 16: 8132-8139.
Gash, D.M., Zhang, Z., Ovadia, A., Cass, W.A., Yi, A., Simmerman, L., Russell, D., Martin, D., Lapchak, P.A., Collins, F., Hoffer, B.J. and Gerhardt, G.A. (1996) Functional recovery in GDNF-treated parkinsonian monkeys. Nature 380: 252-255.