n-3 polyunsaturated fatty acids ameliorate learning and memory abilities in APPPS1 mice by regulating microglial activation and polarization
10.16016/j.2097-0927.202309156
- VernacularTitle:n-3多不饱和脂肪酸调节小胶质细胞激活及极化改善APPPS1小鼠学习记忆能力
- Author:
Mengyan DENG
1
;
Xiaohui ZHU
;
Li HUANG
;
Qian BAI
;
Weifang LI
;
Bin WANG
;
Mantian MI
Author Information
1. 400038 重庆,陆军军医大学(第三军医大学)军事预防医学系营养与食品安全研究中心,重庆市医学营养研究中心,营养与健康重庆市重点实验室
- Keywords:
n-3 polyunsaturated fatty acids;
Alzheimer's disease;
neuroinflammation;
microglia
- From:
Journal of Army Medical University
2024;46(9):928-939
- CountryChina
- Language:Chinese
-
Abstract:
Objective To construct a model of Fat-1/APPPS1 transgenic mice and a cellular model of microglia and explore the improvement effect and underlying mechanism of n-3 polyunsaturated fatty acids(n-3 PUFAs)on the learning and memory abilities of APPPS1 mice by regulating microglial activation and polarization.Methods After the male mice with heterozygous Fat-1 genotype were mated with the female ones with heterozygous APPPS1 genotype,genetic identification was used to screen the male offspring with Fat-1/APPPS1 genotype.Then after the male wild-type(WT)mice and those with Fat-1,Fat-1/APPPS1,and APPPS1 genotypes were bred until 9 months old,their learning and memory abilities were evaluated with Morris water maze(MWM)test.In addition,gas chromatography-mass spectrometry(GC-MS)was performed to detect the concentration of PUFAs in the brain,and immunohistochemistry(IHC)was applied to detect the deposition of β-amyloid protein(Aβ)in the hippocampal regions.Moreover,immunofluorescence assay,qRT-PCR,and enzyme-linked immunosorbent assays(ELISA)were conducted to measure inflammation,and transcription and expression of Iba-1(indicating the microglial activation)and CD86 and CD206(indicating microglial polarization)in central nervous system(CNS).After pretreated with DHA+EPA(25 pmol/mL∶25 μmol/mL),microglial model of inflammatory injury was established in immortalized mouse BV2 cells induced by LPS(1 μg/mL).Afterwards,immunofluorescence assay,qRT-PCR and Western blotting were used to detect inflammation and microglial activation and polarization.Results Compared with the APPPS1 mice,endogenous n-3 PUFAs effectively improved the learning and memory disorders in Fat-1/APPPS1 ones(P＜0.05),remarkably alleviated Aβ deposition in the hippocampal regions(P＜0.05),evidently reduced CNS inflammation and microglial activation(P＜0.05)and transformed the activated microglia from M1 to M2(P＜0.05).Furthermore,BV2 cells with DHA+EPA pretreatment obviously resisted LPS-induced cellular inflammation and induced activated ones from M1 to M2(P＜0.05).Conclusion n-3 PUFAs inhibit the microglial activation,regulate the microglial polarization from M1 to M2,reduce CNS inflammation,and thus alleviate learning and memory disorders in APPPS1 mice.
