Fish oil attenuates methylmalonate-induced seizures

Area of Science:

• Neuroscience
• Metabolic Disorders
• Biochemistry

Background:

• Methylmalonic acidemias (MMA) are inherited metabolic disorders causing neurological dysfunction, notably seizures, due to methylmalonate accumulation.
• Dietary fatty acids, like those in fish oil and oleic acid, show potential in mitigating seizure activity in animal models.

Purpose of the Study:

• To investigate the anticonvulsant effects of chronic fish oil and oleic acid administration on methylmalonic acid (MMA)-induced seizures.
• To determine if these dietary interventions preserve Na(+),K(+)-ATPase activity, a key enzyme in neuronal function.

Main Methods:

• Adult Wistar rats received daily oral doses of fish oil, oleic acid, or vehicle for 75 days.
• Seizure activity was induced by intracerebroventricular injection of MMA and monitored via electroencephalography (EEG) and behavior.
• In vitro assays assessed the impact of prostaglandin E2 (PGE2) on Na(+),K(+)-ATPase activity in cortical slices.

Main Results:

• Fish oil significantly increased the latency to MMA-induced seizures and reduced the mean amplitude of ictal EEG recordings.
• Fish oil administration prevented the decrease in Na(+),K(+)-ATPase activity typically induced by PGE2.
• Oleic acid treatment also reduced the mean amplitude of ictal EEG recordings.

Conclusions:

• Chronic fish oil consumption demonstrates anticonvulsant properties against MMA-induced seizures in rats.
• The neuroprotective effect of fish oil may be linked to its ability to maintain Na(+),K(+)-ATPase activity, potentially through reduced sensitivity to PGE2 inhibition.