A KETOGENIC DIET ENHANCES RESPIRATORY UNCOUPLING AND DECREASES REACTIVE OXYGEN SPECIES PRODUCTION IN MITOCHONDRIA ISOLATED FROM MOUSE CORTEX
Abstract number :
3.029
Submission category :
Year :
2002
Submission ID :
2169
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Patrick G. Sullivan, Nancy A. Rippy, Kristina A. Dorenbos, Oswald Steward, Jong M. Rho. Reeve-Irvine Research Center, University of California at Irvine College of Medicine, Irvine, CA; Department of Pediatrics, University of California at Irvine College
RATIONALE: We have previously observed that a ketogenic diet (KD) increases the survivability of Kcna1-null epileptic mice, suggesting possible neuroprotective effects. We asked whether this observation might be a consequence of enhanced fatty acid-induced respiratory uncoupling, leading to an inhibition of reactive oxygen species (ROS) production which can be damaging to neurons.
METHODS: Normal C3Heb/FeJ mice were fed either the Bio-Serv F3666 KD or normal rodent chow for 10 days beginning at P21-23. The Keto-Site reflectance meter was used to measure blood D-beta-hydroxybutyrate (BHB) levels. Synaptosomal mitochondria were prepared acutely from cortex of mice at P30-31. Mitochondrial uncoupling protein activity and ROS production were assessed through measurements of mitochondrial oxygen consumption and hydrogen peroxide production, respectively.
RESULTS: Mean BHB levels one day prior to sacrifice were 1.2 and 0.68 mM for KD-treated and control diet-fed mice, respectively (p[lt]0.05). Mitochondrial uncoupling protein activity was increased by 70% in KD-treated compared to control diet-fed mice. Additionally, a KD reduced oligomycin-induced ROS production by 17% compared to normal diet-treated mice.
CONCLUSIONS: An experimental KD increases mitochondrial uncoupling activity and decreases ROS production in the cortex of normal juvenile mice, suggesting that this dietary therapy may be neuroprotective as well as anticonvulsant.
[Supported by: NeoTherapeutics Fellowship (P.G.S.), NIH NS 32280 (O.S.), and NIH K08 NS 01974 (J.M.R.)]