RESUMO
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.