Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Female Mice Susceptibility to the Dietary Omega-3/Omega-6 Fatty Acid Ratio: Effects on Adult Hippocampal Neurogenesis and Glia

Version 1 : Received: 18 February 2022 / Approved: 22 February 2022 / Online: 22 February 2022 (09:44:55 CET)

A peer-reviewed article of this Preprint also exists.

Rodríguez-Iglesias, N.; Nadjar, A.; Sierra, A.; Valero, J. Susceptibility of Female Mice to the Dietary Omega-3/Omega-6 Fatty-Acid Ratio: Effects on Adult Hippocampal Neurogenesis and Glia. Int. J. Mol. Sci. 2022, 23, 3399. Rodríguez-Iglesias, N.; Nadjar, A.; Sierra, A.; Valero, J. Susceptibility of Female Mice to the Dietary Omega-3/Omega-6 Fatty-Acid Ratio: Effects on Adult Hippocampal Neurogenesis and Glia. Int. J. Mol. Sci. 2022, 23, 3399.

Journal reference: Int. J. Mol. Sci. 2022, 23, 3399
DOI: 10.3390/ijms23063399

Abstract

Maternal intake of the polyunsaturated fatty acids omega-3 (n-3 PUFA) and omega-6 (n-6 PUFA) impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). n-3 PUFA and n-6 PUFA are precursors of inflammatory regulators that potentially affect AHN and glia. Additionally, n-3 PUFA dietary supplementation may present a sexually dimorphic action in the brain. Therefore, we postulated that dietary n-6/n-3 PUFA balance shapes the adult DG in a sex-dependent manner influencing AHN and glia. We test our hypothesis by feeding adult female and male mice with n-3 PUFA balanced or deficient diets. To analyze the immunomodulatory potential of the diets, we injected mice with the bacterial endotoxin lipopolysaccharide (LPS). LPS reduced neuroblast number, and its effect was exacerbated by the n-3 PUFA deficient diet. The n-3 PUFA deficient diet reduced the DG volume, AHN, microglia number and surveilled volume. Diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, and the sexual dimorphic effect of diet. Our study reveals that female mice are more susceptible than males to the effect of dietary n-6/n-3 PUFA ratio on AHN and microglia.

Keywords

adult neurogenesis; dentate gyrus; diet; microglia; bacterial endotoxin lipopolysaccharide; LPS; Omega 3; polyunsaturated fatty acids; sexual dimorphism; systemic inflammation

Subject

LIFE SCIENCES, Cell & Developmental Biology

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