Effect of activated microglia induced by LCN2 on depression pathogenesis in rats / 医学研究生学报

ABSTRACT

Objective Lipocalin-2(LCN2) can promote the M1 approach of microglia.The study was to explore the effect of activated microglia induced by LCN 2 on depression pathogenesis in rats and its mechanism . Methods According to the chronic stress depression model created by Willner , 40 adult male SD rats were divided into 4 groups(n=10) normal control group;UCMS group;UCMS+LCN2 siRNA group;LCN2 siRNA control group .A series of stress stimulation was given on UCMS group and UCMS +LCN2 siRNA group for 21 days to create depression model .At 7 days after the stress stimulation , the rats in UCMS+LCN2 siRNA group and LCN2 siRNA control group were anaesthetized by 0.4mg intraperitoneal injection of 10% chloral hydrate , followed by intrathecal injection of LCN2 siRNA(0.015 μL/g, 3 times a week) to the rats till the end of the stress (21 days).At the same time, the same volume of isotonic saline was given to normal control group and UCMS group .The weight of rats was measured every week and the sucrose preference and the forced swimming test were applied to measure behavior of the rats after the experiment .The hippocampus of the rats were extracted and immunofluorescence and western blot were applied to detect the expressions of microglia specific markersLCN2 and the Iba. Results At 3 week, the weight of rats in UCMS+LCN2siRNA group was higher than that of UCMS group ([262.82 ±0.01]g vs [179.98 ±0.08]g, P<0.05).The weight of rats in normal control group and LCN2 SiRNA control group increased significantly higher than the other two groups (P<0.05).The sucrose preference values of normal control group (0.82 ±0.01),UCMS+LCN2 siRNA group(0.81 ±0.01) and LCN2 siRNA control group(0.82 ±0.01) were higher than that of UCMS group (0.25 ±0.04) (P<0.05).The fixed time of the forced swimming test of UCMS+LCN2siRNA group decreased significantly compared with UCMS group ([4.64 ±0.8]s vs [23.11 ±2.63]s, P<0.05).The LCN2 expression of UCMS group was significantly greater than the other groups (P<0.05).The Iba1 expression in the hippocampus of the UCMS group increased significantly compared with other groups . Conclusion LCN2 is associated with the pathogenesis of de-pression induced by chronic stress reaction and is mechanism may be related to the activation of microglia in the central nervous system of rats.