Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors
Article first published online: 2 APR 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 114, Issue 1, pages 130–141, July 2010
How to Cite
Kim, D. Y., Vallejo, J. and Rho, J. M. (2010), Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors. Journal of Neurochemistry, 114: 130–141. doi: 10.1111/j.1471-4159.2010.06728.x
- Issue published online: 8 JUN 2010
- Article first published online: 2 APR 2010
- Received December 14, 2009; revised manuscript received March 25, 2010; accepted March 26, 2010.
- mitochondrial respiratory complex;
- neurodegenerative disease;
- oxidative stress;
- synaptic transmission
J. Neurochem. (2010) 114, 130–141.
Ketones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose-dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre-treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant-induced PS recovery against the MRC II inhibitor 3-nitropropionic acid (3-NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3-NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3-NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation.