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

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
• kainate
• seizures
• glutamate transporters
• hippocampus
• memory deficit
• astrogliosis
• anxiety-like behavior

Author contributions

J.D.M participate in the manuscript writing, study concept and design, data collection, analysis, and interpretation of data. L.V.S. and V.M.L participated in data collection, analysis, and interpretation of data. A.P.M, L.O.P and L.V. participated in the manuscript writing, analysis, and interpretation of data. D.O.S was responsible for funding acquisition, study concept and design, manuscript writing, analysis, and interpretation of data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Conselho Nacional de Desenvolvimento Científico e tecnológico (INCT for Excitotoxicity and Neuroprotection - CNPq/INCT); Financiadora de Estudos e Projetos (FINEP/FADESP IBN.Net Proc. no 01.06.0842-00).

Notes on contributors

Júlia D. Moreira

Júlia D. Moreira, PhD, is a professor in Department of Nutrition, Universidade Federal de Santa Catarina.

Letícia Vicari Siqueira

Letícia Vicari Siqueira is a Registered Dietitian. Researcher in Department of Biochemistry, Universidade Federal do Rio Grande do Sul.

Alexandre P. Müller

Alexandre P. Müller, PhD, professor in Postgraduate Program in Pharmacology, Universidade Federal de Santa Catarina.

Lisiane O. Porciúncula

Lisiane O. Porciúncula, PhD, is a professor in Department of Biochemistry, Universidade Federal do Rio Grande do Sul.

Lúcia Vinadé

Lúcia Vinadé, PhD, is a professor in Master Graduation Program in Biological Sciences, UNIPAMPA.

Diogo O. Souza

Diogo O. Souza, PhD, is a professor in Department of Biochemistry, Universidade Federal do Rio Grande do Sul.