The first two authors contributed equally to this work.
Acetoacetate protects neuronal cells from oxidative glutamate toxicity
Article first published online: 24 JAN 2006
copyright © 2006 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 83, Issue 4, pages 702–709, March 2006
How to Cite
Noh, H. S., Hah, Y.-S., Nilufar, R., Han, J., Bong, J.-H., Kang, S. S., Cho, G. J. and Choi, W. S. (2006), Acetoacetate protects neuronal cells from oxidative glutamate toxicity. J. Neurosci. Res., 83: 702–709. doi: 10.1002/jnr.20736
- Issue published online: 23 FEB 2006
- Article first published online: 24 JAN 2006
- Manuscript Revised: 27 OCT 2005
- Manuscript Accepted: 27 OCT 2005
- Manuscript Received: 2 AUG 2005
- Korea Science and Engineering Foundation. Grant Number: R13-2005-012-01001
- ketogenic diet;
Glutamate cytotoxicity contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. We previously reported that a high-fat and low-carbohydrate diet, the ketogenic diet (KD), protects against kainic acid-induced hippocampal cell death in mice. We hypothesized based on these findings that ketosis resulting from KD might inhibit glutamate cytotoxicity, resulting in inhibition of hippocampal neuronal cell death. Therefore, we investigated the role of ketone bodies [acetoacetate (AA) and β-hydroxybutyrate (β-OHB)] both in a mouse hippocampal cell line (HT22) and in rat primary hippocampal neurons. As a result, we found that pretreatment with 5 mM lithium AA and 4 mM Na β-OHB protected the HT22 hippocampal cell line and primary hippocampal neuronal culture against 5 mM glutamate toxicity and that up to 2 hr of pretreatment with 5 mM AA had a protective effect against 5 mM glutamate toxicity in the HT22 cell line. Pretreatment with 5 mM AA decreased ROS production of HT22 cell line at 2 and 8 hr exposure of glutamate, and it decreased the appearance of annexin V-positive HT22 cells, which are indicative of an early stage of apoptosis, and propidium iodide-positive HT22 cells, which are indicative of necrosis. © 2006 Wiley-Liss, Inc.