Exploring mechanisms underlying dopamine neuron vulnerability in Parkinson's disease
Dopamine is critically involved in a multitude of neurodegenerative and neuropsychiatric disorders, including Parkinson’s disease. Motor symptoms in Parkinson's disease result from loss of nigrostriatal dopamine neurons. However, not all dopamine neurons degenerate during the disease: subpopulations of nigrostriatal neurons are less vulnerable than others.
It has been a longstanding puzzle why not all dopamine neurons degenerate in the disease. We still do not completely understand the factors that make some neurons vulnerable while others are resilient, but evidence suggests that different dopamine neuron subtypes are endowed with different molecular and physiological characteristics, e.g. dopamine neurons spared in Parkinson's disease commonly express the calcium binding protein, calbindin, whilst vulnerable ones do not. Better insight into the normal workings of vulnerable compared to resilient DA neurons may hold the key to understanding, and ultimately preventing, neurodegeneration in PD.
Work in our lab uses real-time electrochemical techniques to explore how dopamine transmission from axon terminals in the striatum become altered prior to the emergence of pathology in Parkinson's disease and the mechanisms underlying these changes.
Projects we are currently exploring:
- Exploring the underlying mechanisms that underpin early changes in dopamine transmission in novel rodent models of Parkinson's disease
- Investigating how different forms of alpha synuclein might regulate dopamine transmission