Linked Life Data

19285044

Source:http://linkedlifedata.com/resource/pubmed/id/19285044

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-4-13
pubmed:abstractText
The ketogenic diet has long been recognized as an effective treatment for medically refractory epilepsy. Despite nearly a century of use, the mechanisms underlying its clinical efficacy remain unknown. One of the proposed hypotheses for its anti-epileptic actions involves increased GABA concentration in the brain due to ketone bodies that become elevated with a ketogenic diet. In recent years, the notion that astrocytes could play a role in the evolution of abnormal cortical excitability in chronic neurological disorders, such as epilepsy, has received renewed attention. The present study examined the effects of beta-hydroxybutyrate, a ketone body, on GABA metabolism in rat primary cultured astrocytes. When beta-hydroxybutyrate was added to culture medium, GABA-transaminase (GABA-T) mRNA expression was significantly suppressed in time- and dose-dependent manners. GABA-T enzymatic activity in beta-hydroxybutyrate-treated astrocytes was also suppressed, in accordance with its gene expression. These effects were evident after 3 days of culture, which might coincide with depleted intracellular glycogen. GABA transporter, GAT-1, gene expression was strongly suppressed in cultured astrocytes after 5 days of culture with beta-hydroxybutyrate, although other type of GABA transporters did not display significant changes. These results suggest that beta-hydroxybutyrate induced by ketogenic diet may increase GABA concentration in the epileptic brain by suppressing astrocytic GABA degradation, leading to antiepileptic effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1872-6240
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
1268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-23
pubmed:meshHeading
pubmed-meshheading:19285044-3-Hydroxybutyric Acid, pubmed-meshheading:19285044-4-Aminobutyrate Transaminase, pubmed-meshheading:19285044-Analysis of Variance, pubmed-meshheading:19285044-Animals, pubmed-meshheading:19285044-Astrocytes, pubmed-meshheading:19285044-Butyric Acid, pubmed-meshheading:19285044-Cell Survival, pubmed-meshheading:19285044-Cells, Cultured, pubmed-meshheading:19285044-GABA Plasma Membrane Transport Proteins, pubmed-meshheading:19285044-Gene Expression, pubmed-meshheading:19285044-Glucose, pubmed-meshheading:19285044-RNA, Messenger, pubmed-meshheading:19285044-Rats, pubmed-meshheading:19285044-Rats, Wistar, pubmed-meshheading:19285044-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19285044-Time Factors, pubmed-meshheading:19285044-gamma-Aminobutyric Acid
pubmed:year
2009
pubmed:articleTitle
Beta-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes.
pubmed:affiliation
Department of Pediatrics, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't