Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Excitotoxicity and mitochondria.

D G Nicholls1, S L Budd, M W Ward

  • 1Department of Pharmacology and Neuroscience, University of Dundee, U.K.

Biochemical Society Symposium
|September 16, 2000
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mitochondrial clearance of calcium facilitated by MICU2 controls insulin secretion.

Molecular metabolism·2021
Same author

The value of the lateral view of the rectosigmoid.

The Journal of the Faculty of Radiologists. Faculty of Radiologists (Great Britain)·2014
Same author

Compartmentation of glutamate and aspartate within cerebral cortical synaptosomes: evidence for a non-cytoplasmic origin for the calcium-releasable pool of glutamate.

Neurochemistry international·2010
Same author

Homologues of a K(+) channel blocker ?-dendrotoxin: characterization of synaptosomal binding sites and their coupling to elevation of cytosolic free calcium concentration.

Neurochemistry international·2010
Same author

Methylmalonate inhibits succinate-supported oxygen consumption by interfering with mitochondrial succinate uptake.

Journal of inherited metabolic disease·2008
Same author

'Mild Uncoupling' does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress.

Journal of neurochemistry·2007

Excitotoxicity, a process involving massive glutamate release, causes neuron death. This study reveals that mitochondrial depolarization, not calcium overload, is key to delayed calcium deregulation and neuronal necrosis in excitotoxicity.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Excitotoxicity, triggered by excessive glutamate release during ischemia or trauma, causes delayed neuronal death.
  • Mitochondria play a critical role by accumulating calcium via N-methyl-D-aspartate receptors, leading to neuronal demise.
  • This process is implicated in both acute injury and chronic neurodegenerative diseases.

Purpose of the Study:

  • To investigate the role of mitochondria and calcium regulation in excitotoxicity.
  • To elucidate the mechanisms underlying delayed calcium deregulation (DCD) in cultured cerebellar granule cells.
  • To determine the relationship between mitochondrial function, ATP levels, and excitotoxic neuronal death.

Main Methods:

  • Exposure of cultured cerebellar granule cells to glutamate.

Related Experiment Videos

  • Inhibition of ATP synthase (oligomycin) and mitochondrial respiratory chain.
  • Measurement of intracellular and mitochondrial calcium levels.
  • Assessment of mitochondrial membrane potential and ATP production.
  • Analysis of superoxide anion generation.

    • Main Results:

    • Glutamate exposure induced delayed calcium deregulation (DCD) and necrosis in cultured cerebellar granule cells.
    • DCD was inhibited by mitochondrial depolarization (respiratory chain inhibition) without ATP depletion.
    • Immediate calcium deregulation, caused by ATP depletion, was reversible with oligomycin, unlike DCD.
    • Mitochondrial depolarization occurred after DCD onset, suggesting it's a consequence, not a cause.
    • Enhanced mitochondrial superoxide anion generation was observed during glutamate exposure.

    Conclusions:

    • Mitochondrial depolarization, rather than sustained calcium accumulation, is crucial for excitotoxic neuronal death.
    • Oxidative damage to plasma membrane calcium extrusion pathways is a potential cause of DCD.
    • These findings offer new insights into the mechanisms of excitotoxicity and potential therapeutic targets.