Distinct effects of resveratrol on seizures and hyperexcitability induced by NMDA and 4-aminopyridine

Abstract

Objectives: The antiepileptic activity of resveratrol has been revealed in various experimental models of epilepsy. The present study evaluated the effects of resveratrol on the seizures and hyperexcitable neuronal activity associated with activation of N-methyl-d-aspartic acid (NMDA) receptor and inhibition of voltage-gated potassium channels.

Methods: The effects of resveratrol on seizure thresholds, excitatory field potentials (EFPs) and action potentials induced by NMDA and 4-aminopyridine (4-AP) were monitored in mice, the mouse cortical slices and rat cortical neurons, respectively.

Results: Resveratrol increased the NMDA-induced seizure thresholds and suppressed the frequency of NMDA/glycine-evoked EFPs and action potentials. However, resveratrol lowered the 4-AP-induced thresholds for myoclonic twitch and face and forelimb clonus, yet enhanced the thresholds for running and bouncing clonus and tonic hindlimb extension at the higher dose (50 mg/kg). A similar biphasic response of resveratrol was observed in the frequency of EFPs and action potential firings evoked by 4-AP, with enhancement at lower concentrations, but suppression at higher concentrations.

Discussion: These findings suggest that resveratrol might be capable of protecting against the seizure types related to neuronal excitability and progression mediated by NMDA receptor activation, but not suitable for the seizures caused by disturbance of the voltage-dependent potassium channels.

Keywords:

• Epilepsy
• Action potential
• Excitatory field potentials
• Voltage-gated potassium channels
• Cortical neurons

Availability of data and materials

Data available on request.

Acknowledgements

The authors thank Ms Mei-Yi Lee for outstanding technical assistance.

Disclaimer statement

Contributions YJW, MHC, and HHC conceived the study; YJW, CPH, MHC, and HHC are responsible for experimental design; TYC performed the seizure induction; LC participated in the cell isolation and culture; YJW and CPH performed electrophysiology experiments and data analysis, YJW and CPH prepared the figures and drafted the manuscript; MHC and HHC edited the manuscript.

Conflicts of interest None.

Ethics approval All experiments were performed in accordance with the Republic of China animal protection law (Chapter III: Scientific Application of Animals) and approved by Institutional Animal Care and Use Committee of the National Health Research Institutes (NHRI-IACUC-102038-A).

ORCID

Hwei-Hisen Chen http://orcid.org/0000-0002-8509-6448

Additional information

Funding

This work was supported by a grant (NP-103-PP-02) from the National Health Research Institutes, Taiwan.