Docosahexaenoic acid provides a protective effect in amygdala-kindled rats by activating peroxisome proliferator-activated receptor α.

INTRODUCTION

Docosahexaenoic acid (DHA) is a bioactive fatty acid with safe and acceptable anti-seizure activity in clinical and animal studies. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, with a high rate of drug resistance. The peroxisome proliferator-activated receptor α (PPARα) is expressed in the brain and plays a significant role in oxidative stress, energy homeostasis, and mitochondrial fatty acid metabolism. We aimed to evaluate the acute effect of DHA on the amygdala-kindled seizures and the role of PPARα in the DHA effect.

METHODS

Male rats were kindled by repetitive daily electrical stimulation of the amygdala through a stimulating-recording electrode. DHA 1 mM (alone, or along with the PPARα antagonist GW6471, 2 and/or 4 μg/rat) was injected into the lateral cerebral ventricle of the kindled rats. The amygdala-kindled seizures were evoked 15 and 30 min after drug administration. The duration of after-discharges (ADD), generalized seizure behavior (S5D), and total seizure behavior (SD) were recorded.

RESULTS

DHA significantly decreased ADD (p < 0.05), S5D (p < 0.05), SD (p < 0.05), and incidence of S5 (p < 0.05). GW6471 2 μg/rat did not change seizure parameters but at 4 μg/rat significantly increased ADD (p < 0.001). GW6471 2 μg/rat diminished the anticonvulsant effect of DHA.

CONCLUSION

Acute administration of DHA inhibits amygdala-kindled seizures by activating PPARα. Although PPARα is a nuclear receptor, it partly mediates the acute anti-seizure effect of DHA by rapid non-genomic changes in cellular function. This finding reveals another characteristic of the remarkable omega-3 fatty acid, DHA.