Rodríguez-Iglesias Noelia, Nadjar Agnes, Sierra Amanda, Valero Jorge
Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, E-48940 Leioa, Spain.
Department of Neuroscience, University of the Basque Country UPV/EHU, E-48940 Leioa, Spain.
Int J Mol Sci. 2022 Mar 21;23(6):3399. doi: 10.3390/ijms23063399.
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.
母体摄入omega-3（n-3多不饱和脂肪酸）和omega-6（n-6多不饱和脂肪酸）多不饱和脂肪酸会影响发育过程中的海马神经发生，这种影响可能通过改变成年海马神经发生（AHN）而延续至成年期。n-3多不饱和脂肪酸和n-6多不饱和脂肪酸是炎症调节因子的前体，可能影响AHN和神经胶质细胞。此外，膳食补充n-3多不饱和脂肪酸可能在大脑中呈现出性别二态性作用。因此，我们推测膳食中n-6/n-3多不饱和脂肪酸平衡以性别依赖的方式塑造成年齿状回，影响AHN和神经胶质细胞。我们通过给成年雌性和雄性小鼠喂食n-3多不饱和脂肪酸平衡或缺乏的饮食来检验我们的假设。为了分析饮食的免疫调节潜力，我们给小鼠注射细菌内毒素脂多糖（LPS）。LPS减少了神经母细胞数量，n-3多不饱和脂肪酸缺乏的饮食加剧了其作用。n-3多不饱和脂肪酸缺乏的饮食减少了齿状回体积、AHN、小胶质细胞数量和监测体积。饮食对大多数成熟神经母细胞的影响仅在雌性小鼠中显著。共定位和多变量分析揭示了小胶质细胞与AHN之间的关联以及饮食的性别二态性作用。我们的研究表明，雌性小鼠比雄性小鼠更容易受到膳食n-6/n-3多不饱和脂肪酸比例对AHN和小胶质细胞影响的影响。
