Age-dependent decline of somatodendritic morphology in dopamine neurons from the MitoPark mouse model of Parkinson’s disease

Identification: Beckstead, Mike

Age-dependent decline of somatodendritic morphology in dopamine neurons from the MitoPark mouse model of Parkinson's disease
Michael J. Beckstead1*, William B. Lynch1, Christopher W. Tschumi1, Sarah Y. Branch2, Senlin Li3, Amanda L. Sharpe4
1Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104; 2Department of Cellular and Integrative Physiology, and 3Department of Medicine, University of Texas Health, San Antonio, TX, 78229; 4Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, OK, 73117  
Parkinson's disease is characterized by the progressive loss of dopamine neurons in the substantia nigra, leading to severe motor impairments. While it is thought that dopamine neuron degeneration begins to develop years before observable motor symptoms, the specific morphological and functional changes that contribute to this cellular decline are poorly understood. To address this gap in knowledge we are studying dopamine neuron decline in a mouse model of Parkinson's disease termed MitoPark. MitoPark mice lack the gene coding for mitochondrial transcription factor A (Tfam) specifically in dopamine neurons, which across age produces a progressive decline of neuronal function and related behavior. Our previous work identified an increased membrane resistance and a decreased cell capacitance in dopamine neurons from MitoPark mice, possibly suggesting a reduction in membrane surface area resulting from shrinking morphology. Here we used immunohistochemistry and confocal imaging to quantify morphological decline within nigral dopamine neurons in aging MitoPark mice. The decline preceded wholesale dopamine cell loss in the substantia nigra, and soma size may have been affected slightly prior to dendritic branching. In general, the decline proceeded similarly in mice of both sexes. These results could help identify an ideal time window for specific treatments targeting somatodendritic structure and function that could most effectively alter disease progression and avert debilitating motor deficits in Parkinson's patients.
Funding: R01 AG52606 from the National Institutes of Health, William & Ella Owens Medical Research Foundation, Presbyterian Health Foundation, Oklahoma Center for Adult Stem Cell Research.


Credits: None available.