| The ketogenic diet changes metabolite levels in hippocampal extracellular fluid. | |
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MedLine Citation:
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PMID: 21070829 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Despite successful use of the ketogenic diet (KD) for the treatment of drug-resistant epilepsy, its mechanism of action is unclear. After KD-feeding, increased plasma D-beta-hydroxybutyrate (BHB) levels appear to be important for protection against seizures. We hypothesized that the KD leads to metabolic changes in the brain, which are reflected in the hippocampal extracellular fluid (hECF). CD1 mice were fed control or KD for 2-3 weeks since weaning. In vivo microdialysis of hECF was used to measure the levels of glucose, lactate, as well as BHB under basal conditions and during 30 min stimulation with 60 mM K(+), which was retrodialysed. The hECF BHB concentration in KD-fed mice was determined as 43.4±10.1 μM using the zero-flow method and 50.7±5.5 μM based on in vitro recovery. The total BHB concentration in brain homogenate from KD-fed mice was 180 nmol/g. The intracellular BHB concentration is therefore estimated to be about 3-fold higher than the extracellular level, which suggests that BHB in adolescent mouse brains may not be quickly metabolized. The basal hECF glucose concentration was 30% lower in KD-fed mice, indicating that glucose may be less important as an energy source. Lactate levels were similar in control and KD-fed mice. High potassium stimulation elevated lactate by 3-3.5-fold and decreased glucose by 40-50% in both diet groups, consistent with similar anaerobic and aerobic metabolism in both diet groups during high hippocampal activity. Overall, these data (1) defined the BHB concentration in the hippocampal extracellular fluid in KD-fed mice and (2) showed lower glucose metabolism compared to control diet-fed mice. This work will now enable other researchers to mimic the hippocampal extracellular environment in experiments aimed at deciphering the mechanisms of the KD. |
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Authors:
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Ramakrishna Samala; Jochen Klein; Karin Borges |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-09 |
Journal Detail:
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Title: Neurochemistry international Volume: 58 ISSN: 1872-9754 ISO Abbreviation: Neurochem. Int. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8006959 Medline TA: Neurochem Int Country: England |
Other Details:
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Languages: eng Pagination: 5-8 Citation Subset: IM |
Copyright Information:
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Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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