Pterostilben upregulates GAD67-mediated GABA synthesis in hippocampal parvalbumin-positive cells

Abstract

Background and purpose

Pterostilbene (PTE, 3,5-dimethoxy-4′-hydroxystilbene) is a naturally occurring polyphenol which has antiepileptic properties, and can be utilized as a prophylaxis in patients with seizures and who are at risk of developing epilepsy. However, the effects of PTE on the gamma-aminobutyric acid (GABA)-mediated (GABAergic) nervous system are poorly understood. This study aimed to evaluate the effects of PTE on the GABAergic neurons.

Experimental approach

Male Long-Evans rats were orally administered PTE (200 mg/kg, 5 % Tween 80 in saline) for 10 days using a plastic sonde. The control group was treated with 5 % Tween 80 in saline in a similar manner. Approximately 24 h after the last treatment, we fixed and removed the brains and examined GABA, GAD67, and GAD65 expression in the hippocampal layers using immunohistochemical analysis. In addition, changed GAD expression was compared between the two main GABAergic subtypes, PV⁺ and SOM⁺ cells.

Key results

We demonstrated that PTE treatment increased GABA expression in the hippocampus. These effects can be attributed to GAD67-mediated GABA synthesis in the PV⁺ cells.

Conclusions and implications

Our results uncovered that PTE increased GABA synthesis, suggesting that PTE has potential as a prophylactic drug for patients at risk of developing epilepsy.