Pain & Central Nervous System Week via NewsEdge :

2008 JUL 7 - (NewsRx.com) -- Researchers detail in 'Valproate-dependent transcriptional regulation of GLAST/EAAT1 expression: involvement of Ying-Yang 1,' new data in life sciences (see also Life Sciences). "Valproate, a widely used anti-epileptic drug also employed in the treatment of neurological diseases such as bipolar disorder and migraine, regulates the glutamatergic and GABAergic systems, although its effects in cell physiology have not been thoroughly characterized. High concentrations of glutamate reached during abnormal neurotransmission if not removed properly, become neurotoxic," scientists in Mexico report.

"Glutamate clearance is carried out by high affinity Na(+)-dependent glutamate transporter systems. The glutamate/aspartate transporter GLAST/EAAT1 plays the major role in glutamate removal and is regulated at different levels: transcription, post-translational modifications and cytoplasmic trafficking. The aim of this work was to gain insight into a plausible effect of valproate in GLAST function. Using cultured Bergmann glia cells from chick cerebellum we demonstrate here that valproate exposure elicits a dual regulatory effect on GLAST. In the short-term, valproate increases its Na(+)-dependent [(3)H]-d-aspartate uptake activity in a cytochalasin B-sensitive manner. Interestingly, a synergism between valproate and a histone deacetylase inhibitor was observed. Long-term valproate treatment up-regulates chglast promoter activity, GLAST mRNA levels, GLAST molecules at the plasma membrane and its uptake activity. Furthermore, valproate induces histone 3 lysine 14 acetylation and regulates Ying-Yang 1 (YY1) transcriptional repression on the chglast promoter," wrote G. Aguirre and colleagues, Instituto Politecnico Nacional.

The researchers concluded: "These results suggest that valproate elicits its effect through its histone deacetylase inhibitor properties."

Aguirre and colleagues published their study in Neurochemistry International (Valproate-dependent transcriptional regulation of GLAST/EAAT1 expression: involvement of Ying-Yang 1. Neurochemistry International, 2008;52(7):1322-31).

For additional information, contact G. Aguirre, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Departamento de Genetica y Biologia Molecular, Cinvestav-IPN, Apartado Postal 14-740, Mexico, DF 07000, Mexico.

The publisher's contact information for the journal Neurochemistry International is: Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England.

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