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Denervation-induced decrease in mitochondrial calcium transport in rat hippocampus.

M Baudry, C Gall, M Kessler

    The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
    |February 1, 1983
    PubMed
    Summary
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    Denervation significantly reduces mitochondrial calcium transport and pyruvate dehydrogenase activity in the hippocampus, impacting calcium regulation long-term. This suggests a link between deafferentation and neurodegenerative processes.

    Area of Science:

    • Neuroscience
    • Cell Biology
    • Mitochondrial Function

    Background:

    • Mitochondria play a crucial role in cellular calcium homeostasis.
    • Pyruvate dehydrogenase (PDH) is a key mitochondrial enzyme involved in energy metabolism.
    • Denervation, a loss of neural input, can profoundly affect neuronal function and cellular processes.

    Purpose of the Study:

    • To investigate the impact of partial denervation on mitochondrial calcium accumulation in the hippocampus.
    • To examine the activity and phosphorylation state of pyruvate dehydrogenase (PDH) in denervated hippocampus.
    • To elucidate the relationship between denervation, mitochondrial calcium handling, and PDH regulation.

    Main Methods:

    • Mitochondrial calcium uptake was measured using both calcium-sensitive electrodes and 45Ca2+ accumulation.

    Related Experiment Videos

  • Pyruvate dehydrogenase (PDH) activity and in vitro phosphorylation were assessed.
  • Lesions of the entorhinal cortex were used to induce partial denervation in the hippocampus.

    • Main Results:

    • Entorhinal cortex lesions significantly reduced mitochondrial calcium transport, particularly when mitochondria were fueled with pyruvate.
    • This reduction in calcium transport was observed as early as 24 hours post-lesion and persisted for 6 months.
    • Both synaptic and nonsynaptic mitochondria were affected, and PDH activity and phosphorylation were also significantly decreased.

    Conclusions:

    • Partial denervation disrupts mitochondrial calcium regulation in the hippocampus.
    • The observed changes suggest an alteration in the phosphorylation state and activity of pyruvate dehydrogenase (PDH) due to denervation.
    • These findings highlight a potential mechanism linking deafferentation-induced mitochondrial dysfunction to neurodegenerative changes.