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- Title
Mitochondrial and Plasma Membrane Potential of Cultured Cerebellar Neurons during Glutamate-Induced Necrosis, Apoptosis, and Tolerance.
- Authors
Ward, Manus W.; Huber, Heinrich J.; Weisová, Petronela; Düssmann, Heiko; Nicholls, David G.; Prehn, Jochen H. M.
- Abstract
A failure of mitochondrial bioenergetics has been shown to be closely associated with the onset of apoptotic and necrotic neuronal injury. Here, we developed an automated computational model that interprets the single-cell fluorescence for tetramethylrhodamine methyl ester (TMRM) as a consequence of changes in either ΔΨm orΔΨp, thus allowing for the characterization of responses for populations of single cells and subsequent statistical analysis. Necrotic injury triggered by prolonged glutamate excitation resulted in a rapid monophasic or biphasic loss of ΔΨm that was closely associated with a loss of ΔΨp and a rapid decrease in neuronal NADPH and ATP levels. Delayed apoptotic injury, induced by transient glutamate excitation, resulted in a small, reversible decrease in TMRM fluorescence, followed by a sustained hyperpolarization of ΔΨm as confirmed using the ΔΨp -sensitive anionic probe DiBAC2(3). This hyperpolarization of ΔΨm was closely associated with a significant increase in neuronal glucose uptake,NADPH availability, and ATP levels. Statistical analysis of the changes in ΔΨm or ΔΨp at a single-cell level revealed two major correlations; those neurons displaying a more pronounced depolarization of ΔΨp during the initial phase of glutamate excitation entered apoptosis more rapidly, and neurons that displayed a more pronounced hyperpolarization of ΔΨm after glutamate excitation survived longer. Indeed, those neurons that were tolerant to transient glutamate excitation (18%) showed the most significant increases in ΔΨm. Our results indicate that a hyperpolarization of ΔΨm is associated with increased glucose uptake, NADPH availability, and survival responses during excitotoxic injury.
- Subjects
MITOCHONDRIAL membranes; CELL membranes; CEREBELLUM; NEURONS; GLUTAMIC acid; NECROSIS; APOPTOSIS
- Publication
Journal of Neuroscience, 2007, Vol 27, Issue 31, p8238
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1984-07.2007