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.. 2022-03-21; 23(6): 3399
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Rodríguez-Iglesias N(1)(2), Nadjar A(3)(4), Sierra A(1)(2)(5), Valero J(1)(6)(7).
(1)Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, E-48940 Leioa, Spain.
(2)Department of Neuroscience, University of the Basque Country UPV/EHU, E-48940 Leioa, Spain.
(3)Neurocentre Magendie, U1215, INSERM-Université de Bordeaux, 33077 Bordeaux, France.
(4)Institut Universitaire de France (IUF), 33077 Bordeaux, France.
(5)Ikerbasque Basque Foundation for Science, E-48009 Bilbao, Spain.
(6)Institute of Neuroscience of Castilla y León (INCyL), University of Salamanca, E-37007 Salamanca, Spain.
(7)Institute for Biomedical Research of Salamanca (IBSAL), E-37007 Salamanca, Spain.
Maternal intake of omega-3 (n-3 PUFAs) and omega-6 (n-6 PUFAs) polyunsaturated fatty acids impacts hippocampal neurogenesis during development, an effect that may extend to adulthood by altering adult hippocampal neurogenesis (AHN). The n-3 PUFAs and n-6 PUFAs 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. The diet effect on most mature neuroblasts was exclusively significant in female mice. Colocalization and multivariate analysis revealed an association between microglia and AHN, as well as 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.