SPONTANEOUS CHANGES IN MITOCHONDRIAL MEMBRANE POTENTIAL

Project Details

Description

Neurodegenerative diseases, such as Parkinson's, are among the most pressing health concerns in the American population and have been linked to excessive glutamatergic activity in the central nervous system. Glutamate, acting at the NMDA receptor complex, allows the influx of Ca2+ into the cell. As [Ca2+]c rises, mitochondria begin to sequester Ca2+. Inhibiting this mitochondrial process significantly improves cell survival. These data implicate mitochondria in neurodegenerative cell death and suggest that mitochondrial physiology and function should be further explored. In the resent proposal, the nature and significance of spontaneous changes in mitochondrial membrane potential (deltapsim) in healthy cultured neurons will be examined. Neurons loaded with deltapsim sensitive fluorescent dyes exhibit spontaneous oscillations in fluorescent intensity in small regions of the neuronal processes. Although numerous cellular and mitochondrial activities are known to influence deltapsim, our primary hypothesis is that deltapsim oscillations reflect compensatory mechanisms of mitochondria to changes in intracellular [Ca2+] or in energy demands and may be accomplished by transient openings of the permeability transition pore. Moreover, mitochondrial dysfunction is known to be critically involved in cascades of events that lead to necrosis and apoptosis, however whether they participate in the initial stages of these death pathways remains unresolved. Using deltapsim oscillations as a marker, mitochondrial function after necrotic r apoptotic stimuli will be followed. These experiments will act as a foundation for the complete assessment of mitochondrial involvement in neurodegenerative cell death.
StatusFinished
Effective start/end date11/16/008/31/01

Funding

  • National Institute of Neurological Disorders and Stroke: $30,494.00

ASJC

  • Clinical Neurology
  • Neurology

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.