Beta-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes
Suzuki, Y; Takahashi, H; Fukuda, M; Hino, H; Kobayashi, K; Tanaka, J; Ishii, E
HERO ID
1454127
Reference Type
Journal Article
Year
2009
Language
English
PMID
| HERO ID | 1454127 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | Beta-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes |
| Authors | Suzuki, Y; Takahashi, H; Fukuda, M; Hino, H; Kobayashi, K; Tanaka, J; Ishii, E |
| Journal | Brain Research |
| Volume | 1268 |
| Page Numbers | 17-23 |
| Abstract | 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. |
| Doi | 10.1016/j.brainres.2009.02.074 |
| Pmid | 19285044 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |