Neuroprotection provided by Omega-3 polyunsaturated fatty acid through inhibiting microglia-mediated neuroinflammatory response in cognitive impairment rats
10.3760/cma.j.issn.1674-635X.2019.01.005
- VernacularTitle:ω-3多不饱和脂肪酸抑制小胶质细胞改善认知功能障碍模型大鼠神经功能
- Author:
Yan YU
1
;
Rupeng SUN
;
Zhifeng WU
;
Yihui QIN
;
Yi LI
Author Information
1. 中国人民解放军第174医院干部病房(老年科)
- Keywords:
Alzheimer's disease;
Cognitive impairment;
Omega-3 polyunsaturated fatty acid;
Microglia;
Inflammatory response;
NF-κB pathway
- From:
Chinese Journal of Clinical Nutrition
2019;27(1):26-32
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and mechanisms of Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation on spatial learning and memory capacity,neuronal apoptosis,microglia activation,neuroinflammatory response and nuclear factor-κB (NF-κB) pathway in cognitive impairment model rats.Methods Cognitive impairment model rats were induced by intraperitoneal injection of D-galactose.Thirty-six Wistar rats were randomly divided into three groups:control group (Con),Cognitive impairment group (AD) and ω-3 PUFA supplementation group (AD+ω-3).The spatial learning and memory capacity of experimental rats were examined by the Morris water maze (MWM).Apoptotic neurons were determined by Nissl staining.The microglia activation relatived protein (Iba-1) expressions was determined by immunohistochemistry staining and western blot,respectively.While,the serum levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-1 and IL-6 were tested by enzyme linked immunosorbent assay (ELISA).In addition,the protein expression of NF-κB related indexes including NF-κB p65,p-IκB and TLR4 were tested using western blot.Results Compared with the Con group,the escape latency increased and the distance percentage in target quadrant decreased;neurons apoptosis,microglia activation and neuroinflammatory factors significantly increased in the other two groups (P=0.00).Compared with the AD group,the escape latency was remarkably shorter (2 d:41.35±2.34vs.58.07±3.27,P=0.03;3 d:35.07±2.45 vs.44.39±3.21,P=0.02;4d:28.12±2.43vs.35.63±2.20,P=0.01;5 d:23.74±1.06 vs.29.76±1.15,P=0.03),and the distance percentage in target quadrant increased significantly [(48.26±4.02)％ vs.(34.14±3.49)％,P =0.01] after ω-3 PUFA supplementation.The incidence of neurons apoptosis significantly decreased in AD + ω-3 group [(29.93 ±3.05) ％ vs.(47.58±4.14)％,P=0.01].ω-3 PUFA supplementation inhibited the protein expression of microglia,and meanwhile inhibed the expression of microglia-induced neuroinflammatory factors [TNF-α:(85.27±9.77vs.156.13±14.53) pg/ml,P=0.00;IL-1:(41.23±5.38vs.75.04±9.27) pg/ml,P=0.01;IL-6:(47.58±4.23 vs.97.47±9.09) pg/ml,P=0.00].Compared with AD group,the protein expression of NF-κB pathway significantly decreased in AD+ω-3 group.Conclusion ω-3 PUFA supplementation can inhibited microglia activation,decrease microglia-mediated neuroinflammatory response,reduce neuron apoptosis and markedly improve spatial learning and memory capacity in cognitive impairment rats,possibly mediated by inhibiting NF-κB pathway.
