Dietary omega-3 fatty acids prevent neonatal seizure-induced early alterations in the hippocampal glutamatergic system and memory deficits in adulthood

Nutr Neurosci. 2022 May;25(5):1066-1077. doi: 10.1080/1028415X.2020.1837569. Epub 2020 Oct 27.

Abstract

Objective: We investigated the influence of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) on glutamatergic system modulation after a single episode of neonatal seizures and their possible effects on seizure-induced long-lasting behavioral deficits.

Methods: Male Wistar rats receiving an omega-3 diet (n-3) or an n-3 deficient diet (D) from the prenatal period were subjected to a kainate-induced seizure model at P7. Glutamate transporter activity and immunocontents (GLT-1 and GLAST) were assessed in the hippocampus at 12, 24, and 48 h after the seizure episode. Fluorescence intensity for glial cells (GFAP) and neurons (NeuN) was assessed 24 h after seizure in the hippocampus. Behavioral analysis (elevated-plus maze and inhibitory avoidance memory task) was performed at 60 days of age.

Results: The D group showed a decrease in glutamate uptake 24 h after seizure. In this group only, the GLT1 content increased at 12 h, followed by a decrease at 24 h. GLAST increased up to 24 h after seizure. GFAP fluorescence was higher, and NeuN fluorescence decreased, in the D group independent of seizures. In adulthood, the D group presented memory deficits independent of seizures, but short-term memory (1.5 h after a training session) was abolished in the D group treated with kainate.

Significance: N-3 PUFA positively influenced the glutamatergic system during seizure and prevented seizure-related memory deficits in adulthood.

Keywords: N-3 PUFA; anxiety-like behavior; astrogliosis; glutamate transporters; hippocampus; kainate; memory deficit; seizures.

MeSH terms

  • Animals
  • Diet
  • Epilepsy*
  • Fatty Acids, Omega-3* / adverse effects
  • Female
  • Glutamic Acid
  • Hippocampus
  • Kainic Acid
  • Male
  • Memory Disorders / prevention & control
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / prevention & control

Substances

  • Fatty Acids, Omega-3
  • Glutamic Acid
  • Kainic Acid