Mitochondria play a critical role in pathogenesis of many neurological disorders, partly because of the unique function of mitochondria in neuronal activity at the synapses and along the axons. In vitro models of neurodegenerative disorders utilizing primary neuronal cultures, explants/slice cultures and neuronal and glial cell lines have been developed to study disease mechanisms and establish assays for drug screening. Role of mitochondria in oxidative stress, axonal degeneration, cell death and neuronal energy metabolism are being studied in these in vitro models, but most of the currently available assays have limitations. Many of the assays on mitochondrial function require isolation of mitochondria from the cells eliminating contribution of intracellular signaling on mitochondrial function. Other assays are indirect and look at consequences of mitochondrial dysfunction and are often static assays. An instrument that evaluates mitochondrial function in real-time within neuronal and glial cells would be of great value to test hypotheses on the relevance of mitochondria in neurodegenerative disease pathogenesis. The Seahorse XF-96 analyzer is such an instrument allowing one to evaluate oxygen consumption rate (OCR) and extracellular acidification rate (ECAR, i.e. proton production) in living cells in real-time. The principal investigator and major users of the proposed XF-96 are all neurologists and neuroscientists studying neurodegenerative disease mechanisms, including motor neuron disease, multiple sclerosis, human immunodeficiency virus (HIV) dementia, and peripheral neuropathies. As outlined in the proposal, the XF-96 analyzer will allow the investigators to measure mitochondrial function in whole neuronal and glial cell populations over time eliminating the need for timed experiments with multiple samples at different time points;thus expediting the research and facilitating explorations of new scientific directions.
The proposed purchase of Seahorse XF96 analyzer will help expedite ongoing studies aimed at understanding the mechanisms of a variety of neurodegenerative diseases, including dementias, motor neuron disease, multiple sclerosis and peripheral neuropathies. These neurodegenerative diseases are among the most common and devastating types of neurological disorders affecting a large segment of the population.
|Dolce, Alison; Santos, Polan; Chen, Weiran et al. (2018) Different ketogenesis strategies lead to disparate seizure outcomes. Epilepsy Res 143:90-97|