Srinivas Vilasagaram, Varma Saikanth, Kona Suryam Reddy, Ibrahim Ahamed, Duttaroy Asim K, Basak Sanjay
Molecular Biology Division, National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500 007, India.
Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway.
Prostaglandins Leukot Essent Fatty Acids. 2023 Apr;191:102566. doi: 10.1016/j.plefa.2023.102566. Epub 2023 Mar 11.
Maternal n-3 PUFA (omega-3) deficiency can affect brain development in utero and postnatally. Despite the evidence, the impacts of n-3 PUFA deficiency on the expression of neurogenesis genes in the postnatal hippocampus remained elusive. Since postnatal brain development requires PUFAs via breast milk, we examined the fatty acid composition of breast milk and hippocampal expression of neurogenesis genes in n-3 PUFA deficient 21d mice. In addition, the expression of fatty acid desaturases, elongases, free fatty acids signaling receptors, insulin and leptin, and glucose transporters were measured. Among the genes involved in neurogenesis, the expression of brain-specific tenascin-R (TNR) was downregulated to a greater extent (∼31 fold), followed by adenosine A2A receptor (A2AAR), dopamine receptor D2 (DRD2), glial cell line-derived neurotrophic factor (GDNF) expression in the n-3 PUFA deficient hippocampus. Increasing dietary LA to ALA (50:1) elevated the ARA to DHA ratio by ∼8 fold in the n-3 PUFA deficient breast milk, with an overall increase of total n-6/n-3 PUFAs by ∼15:1 (p<0.05) compared to n-3 PUFA sufficient (LA to ALA: 2:1) diet. The n-3 PUFA deficient mice exhibited upregulation of FADS1, FADS2, ELOVL2, ELOVL5, ELOVL6, GPR40, GPR120, LEPR, IGF1 and downregulation of GLUT1, GLUT3, and GLUT4 mRNA expression in hippocampus (p<0.05). Maternal n-3 PUFA deficiency affects the hippocampal expression of key neurogenesis genes in the offspring with concomitant expression of desaturase and elongase genes, suggesting the importance of dietary n-3 PUFA for neurodevelopment.
母体n-3多不饱和脂肪酸（omega-3）缺乏会影响子宫内和出生后的大脑发育。尽管有相关证据，但n-3多不饱和脂肪酸缺乏对出生后海马体中神经发生基因表达的影响仍不明确。由于出生后的大脑发育需要通过母乳摄取多不饱和脂肪酸，我们检测了n-3多不饱和脂肪酸缺乏的21日龄小鼠母乳中的脂肪酸组成以及海马体中神经发生基因的表达。此外，还测量了脂肪酸去饱和酶、延长酶、游离脂肪酸信号受体、胰岛素和瘦素以及葡萄糖转运蛋白的表达。在参与神经发生的基因中，脑特异性腱生蛋白-R（TNR）的表达下调幅度更大（约31倍），其次是n-3多不饱和脂肪酸缺乏的海马体中腺苷A2A受体（A2AAR）、多巴胺受体D2（DRD2）、胶质细胞源性神经营养因子（GDNF）的表达。在n-3多不饱和脂肪酸缺乏的母乳中，将膳食中的亚油酸与α-亚麻酸比例提高到50:1，使花生四烯酸与二十二碳六烯酸的比例提高了约8倍，与n-3多不饱和脂肪酸充足（亚油酸与α-亚麻酸比例为2:1）的饮食相比，n-6/n-3多不饱和脂肪酸总量总体增加了约15:1（p<0.05）。n-3多不饱和脂肪酸缺乏的小鼠海马体中FADS1、FADS2、ELOVL2、ELOVL5、ELOVL6、GPR40、GPR120、LEPR、IGF1的表达上调，而GLUT1、GLUT3和GLUT4 mRNA的表达下调（p<0.05）。母体n-3多不饱和脂肪酸缺乏会影响后代海马体中关键神经发生基因的表达，同时伴有去饱和酶和延长酶基因的表达，这表明膳食n-3多不饱和脂肪酸对神经发育具有重要意义。
