The research group led by Dr Mahalakshmi Subramaniam and Prof. Jochen Roeper at the Institute for Neurophysiology at the Goethe University, in collaboration with researchers from Frankfurt’s Experimental Neurology Group and from Freiburg University, has demonstrated for the first time how sensitive dopaminergic substantia nigra neurons functionally respond to toxic proteins in a genetic mouse model. A mutated α-synuclein gene (A53T), which causes Parkinson’s Disease in humans, is expressed in the mouse model.
In the current issue of the Journal of Neuroscience, the researchers report that the sensitive dopaminergic substantia nigra neurons respond to the accumulation of toxic protein by significantly increasing the electric activity in the affected mid-brain regions. In contrast, the less sensitive, neighboring dopaminergic neurons were not affected in their activity. “This process begins as early as one year before the first deficits appear in the dopamine system, and as such it presents an early functional biomarker that may have future potential for preclinical detection of impending Parkinson’s Disease in humans,” explains Prof Jochen Roeper. “The potential for early preclinical detection of subjects at risk is essential for the development of neuroprotective therapies.”
M. Subramaniam, D. Althof, S. Gispert, J. Schwenk, G. Auburger, A. Kulik, B. Fakler, J. Roeper. Mutant-Synuclein Enhances Firing Frequencies in Dopamine Substantia Nigra Neurons by Oxidative Impairment of A-Type Potassium Channels. Journal of Neuroscience, 2014; 34 (41): 13586 DOI: 10.1523/JNEUROSCI.5069-13.2014