Ketone bodies are protective against oxidative stress in neocortical neurons

Do Young Kim, Laurie M. Davis, Patrick G. Sullivan, Marwan Maalouf, Timothy Simeone, Johannes Van Brederode, Jong M. Rho

Research output: Contribution to journalArticle

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Abstract

Ketone bodies (KB) have been shown to prevent neurodegeneration in models of Parkinson's and Alzheimer's diseases, but the mechanisms underlying these effects remain unclear. One possibility is that KB may exert antioxidant activity. In the current study, we explored the effects of KB on rat neocortical neurons exposed to hydrogen peroxide (H2O2) or diamide - a thiol oxidant and activator of mitochondrial permeability transition (mPT). We found that: (i) KB completely blocked large inward currents induced by either H2O2 or diamide; (ii) KB significantly decreased the number of propidium iodide-labeled cells in neocortical slices after exposure to H2O2 or diamide; (iii) KB significantly decreased reactive oxygen species (ROS) levels in dissociated neurons and in isolated neocortical mitochondria; (iv) the electrophysiological effects of KB in neurons exposed to H2O2 or diamide were mimicked by bongkrekic acid and cyclosporin A, known inhibitors of mPT, as well as by catalase and DL - dithiothreitol, known antioxidants; (v) diamide alone did not significantly alter basal ROS levels in neurons, supporting previous studies indicating that diamide-induced neuronal injury may be mediated by mPT opening; and (vi) KB significantly increased the threshold for calcium-induced mPT in isolated mitochondria. Taken together, our data suggest that KB may prevent mPT and oxidative injury in neocortical neurons, most likely by decreasing mitochondrial ROS production.

Original languageEnglish
Pages (from-to)1316-1326
Number of pages11
JournalJournal of Neurochemistry
Volume101
Issue number5
DOIs
StatePublished - Jun 2007

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Ketone Bodies
Oxidative stress
Diamide
Neurons
Oxidative Stress
Permeability
Reactive Oxygen Species
Mitochondria
Bongkrekic Acid
Antioxidants
Propidium
Dithiothreitol
Induced currents
Wounds and Injuries
Sulfhydryl Compounds
Oxidants
Catalase
Hydrogen Peroxide
Cyclosporine
Parkinson Disease

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Kim, D. Y., Davis, L. M., Sullivan, P. G., Maalouf, M., Simeone, T., Van Brederode, J., & Rho, J. M. (2007). Ketone bodies are protective against oxidative stress in neocortical neurons. Journal of Neurochemistry, 101(5), 1316-1326. https://doi.org/10.1111/j.1471-4159.2007.04483.x

Ketone bodies are protective against oxidative stress in neocortical neurons. / Kim, Do Young; Davis, Laurie M.; Sullivan, Patrick G.; Maalouf, Marwan; Simeone, Timothy; Van Brederode, Johannes; Rho, Jong M.

In: Journal of Neurochemistry, Vol. 101, No. 5, 06.2007, p. 1316-1326.

Research output: Contribution to journalArticle

Kim, DY, Davis, LM, Sullivan, PG, Maalouf, M, Simeone, T, Van Brederode, J & Rho, JM 2007, 'Ketone bodies are protective against oxidative stress in neocortical neurons', Journal of Neurochemistry, vol. 101, no. 5, pp. 1316-1326. https://doi.org/10.1111/j.1471-4159.2007.04483.x
Kim, Do Young ; Davis, Laurie M. ; Sullivan, Patrick G. ; Maalouf, Marwan ; Simeone, Timothy ; Van Brederode, Johannes ; Rho, Jong M. / Ketone bodies are protective against oxidative stress in neocortical neurons. In: Journal of Neurochemistry. 2007 ; Vol. 101, No. 5. pp. 1316-1326.
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