کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4328464 | 1614171 | 2009 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
β-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
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 β-hydroxybutyrate, a ketone body, on GABA metabolism in rat primary cultured astrocytes. When β-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 β-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 β-hydroxybutyrate, although other type of GABA transporters did not display significant changes. These results suggest that β-hydroxybutyrate induced by ketogenic diet may increase GABA concentration in the epileptic brain by suppressing astrocytic GABA degradation, leading to antiepileptic effects.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1268, 1 May 2009, Pages 17-23
Journal: Brain Research - Volume 1268, 1 May 2009, Pages 17-23
نویسندگان
Yuka Suzuki, Hisaaki Takahashi, Mitsumasa Fukuda, Hitomi Hino, Kana Kobayashi, Junya Tanaka, Eiichi Ishii,