Neuroprotection provided by Omega-3 polyunsaturated fatty acid through inhibiting microglia-mediated neuroinflammatory response in cognitive impairment rats

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±2.34 vs. 58.07±3.27, P=0.03; 3 d: 35.07±2.45 vs. 44.39±3.21, P=0.02; 4d: 28.12±2.43 vs. 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±9.77 vs. 156.13±14.53)pg/ml, P=0.00; IL-1: (41.23±5.38 vs. 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. Key words: Alzheimer′s disease; Cognitive impairment; Omega-3 polyunsaturated fatty acid; Microglia; Inflammatory response; NF-κB pathway