Ketone bodies are protective against oxidative stress in neocortical neurons
Article first published online: 20 FEB 2007
Journal of Neurochemistry
Volume 101, Issue 5, pages 1316–1326, June 2007
How to Cite
Kim, D. Y., Davis, L. M., Sullivan, P. G., Maalouf, M., Simeone, T. A., Brederode, J. v. and Rho, J. M. (2007), Ketone bodies are protective against oxidative stress in neocortical neurons. Journal of Neurochemistry, 101: 1316–1326. doi: 10.1111/j.1471-4159.2007.04483.x
- Issue published online: 20 FEB 2007
- Article first published online: 20 FEB 2007
- Received September 11, 2006; revised manuscript received November 30, 2006; accepted December 7, 2006.
- ketone bodies;
- mitochondrial permeability transition;
- oxidative stress
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.