Department of Physiology and Pharmacology, CUNY Medical School, New York, NY, USA.
Prev Med. 2012 May;54 Suppl:S103-8. doi: 10.1016/j.ypmed.2011.12.019. Epub 2011 Dec 28.
Autoimmune-prone B-cell activating factor transgenic mice, a mouse model of systemic lupus erythematosus and Sjögren's syndrome exhibit neuroinflammation, anxiety-like phenotype, deficit in adult hippocampal neurogenesis and impaired neurogenesis-dependent and neurogenesis-independent dentate gyrus long-term potentiation. Given that n-3 polyunsaturated fatty acids regulate hippocampal plasticity and inflammatory responses, we investigated whether n-3 polyunsaturated fatty acids-enriched diet might prevent age-dependent hippocampal changes in B-cell activating factor transgenic mice.
B-cell activating factor transgenic mice were fed for 12 weeks with either n-3 polyunsaturated fatty acids-enriched or control diet and we tested the effect of this dietary supplementation on hippocampal inflammation, progenitor cell proliferation and neurogenesis-dependent and neurogenesis-independent long-term potentiation.
Dietary supplementation with n-3 polyunsaturated fatty acids significantly decreased hippocampal microglial activation and increased the density of bromodeoxyuridine and doublecortin-positive newly-formed cells in the subventricular zone of hippocampus. Furthermore, B-cell activating factor transgenic mice fed with n-3 polyunsaturated fatty acids-enriched diet displayed normal long-term potentiation at the medial perforant pathway/dentate gyrus connections.
The results indicate that n-3 fatty acids prevent neuroinflammation and deficits of hippocampal plasticity in B-cell activating factor transgenic mice and suggest that increased n-3 fatty acids intake might represent a potential therapeutic option to prevent neuropsychiatric symptoms associated with autoimmune diseases.
自身免疫倾向的 B 细胞激活因子转基因小鼠是系统性红斑狼疮和干燥综合征的小鼠模型,表现出神经炎症、焦虑样表型、成年海马神经发生缺陷以及神经发生依赖和非依赖的齿状回长时程增强受损。鉴于 n-3 多不饱和脂肪酸调节海马可塑性和炎症反应,我们研究了富含 n-3 多不饱和脂肪酸的饮食是否可以预防 B 细胞激活因子转基因小鼠的年龄依赖性海马变化。
用富含 n-3 多不饱和脂肪酸的饮食或对照饮食喂养 B 细胞激活因子转基因小鼠 12 周,并测试这种饮食补充对海马炎症、祖细胞增殖以及神经发生依赖和非依赖的长时程增强的影响。
富含 n-3 多不饱和脂肪酸的饮食补充显著降低了海马小胶质细胞的激活,并增加了海马下区 BrdU 和双皮质素阳性新生细胞的密度。此外,用富含 n-3 多不饱和脂肪酸的饮食喂养的 B 细胞激活因子转基因小鼠在中隔侧穿孔通路/齿状回连接处显示出正常的长时程增强。
这些结果表明,n-3 脂肪酸可预防 B 细胞激活因子转基因小鼠的神经炎症和海马可塑性缺陷,并提示增加 n-3 脂肪酸的摄入可能是预防与自身免疫性疾病相关的神经精神症状的潜在治疗选择。