Effect of diesel exhaust particulate matter exposure on anxious- and depressive- like behaviors in hypertensive model mice and the mechanism of microglial polarization
10.3760/cma.j.cn371468-20241230-00625
- VernacularTitle:柴油尾气颗粒物暴露对高血压模型小鼠焦虑抑郁样行为的影响及小胶质细胞极化的机制研究
- Author:
Yu WU
1
;
Han HAO
;
Bingrui LIU
;
Weixuan WANG
;
Yanshu ZHANG
;
Jianzhu BO
Author Information
1. 华北理工大学公共卫生学院，唐山 063210
- Publication Type:Journal Article
- Keywords:
Diesel exhaust particulate matter;
Hypertension;
Triggering receptor expressed on myeloid cells 2/insulin-like growth factor 1;
Microglial polarization;
A
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2025;34(7):583-590
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of microglial polarization modulated by triggering receptor expressed on myeloid cells 2/insulin-like growth factor-1(TREM2/IGF-1) in hypertensive model mice exposed to diesel exhaust particulate matter (DPM), with a focus on its implications for anxious- and depressive-like behaviors.Methods:SPF-grade male C57BL/6J mice were divided into the control group, the hypertension group, the DPM group, and the hypertension+ DPM group according to the principle of weight-matching, with 10 mice in each group. The hypertension model was established by intraperitoneal injection of angiotensin Ⅱ (AngⅡ) in hypertension group and hypertension+ DPM group, and mice in the control group and DPM group were intraperitoneally injected with an equivalent amount of 0.9% NaCl solution.DPM suspension was instilled into the nasal cavity of the mice in DPM group and hypertension+ DPM group(1 μg/μL, 10 μL, once a day for 56 days).Behavioral tests, including the sucrose preference test, tail suspension test, elevated plus maze test, and open field test, were conducted to evaluate anxious- and depressive-like behaviors.TREM2-overexpressing BV2 cell model was established through plasmid transfection technology.Western blot was applied to measure the protein expression of IL-1β, IL-6, TNF-α, iNOS, Arg-1, TREM2 and IGF-1.SPSS 23.0 software was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for post-hoc testing. Results:(1)There were statistically significant differences in the sucrose preference rate, immobility time in the tail suspension test, percentage of time and number of entries into the open arms in the elevated plus maze, as well as the total distance, percentage of time spent in the central area in the open field test among the four groups of mice( F=22.82, 21.60, 36.17, 20.99, 5.85, 13.24, all P<0.01).The sucrose preference rate, percentage of time spent in the open arms, percentage of number of entries into the open arms, total distance and percentage of time spent in the central area of the DPM group and the hypertension group were lower than those of the control group( P<0.05), while the immobility time of the two group was higher than that of the control group( P<0.05). The sucrose preference rate((55.62±4.46)%) and percentage of time spent in the open arms((4.17±0.62)%) of the hypertension+ DPM group were lower than those of the DPM group((60.78±3.21)%, (6.44±0.89)%) and the hypertension group((66.26±4.25)%, (6.53±1.29)%)(all P<0.05), while the immobility time((155.42±12.50)s) was higher than that of the DPM group((129.03±5.43)s) and the hypertension group((129.28±10.55)s)(both P<0.05).(2)Western blot analysis revealed statistically significant differences in protein expression of IL-1β, IL-6, TNF-α, iNOS, Arg-1, and TREM2/IGF-1 in the medial prefrontal cortex(mPFC) among the four experimental groups( F=12.23, 10.51, 33.89, 145.40, 11.85, 15.56, 33.11, all P<0.05).The hypertension+ DPM group demonstrated significantly higher protein expression of IL-1β and IL-6 compared to the hypertension group (all P<0.05). Relative to the hypertension+ DPM group, TNF-α and iNOS protein expression was elevated in both the hypertension group and DPM group, whereas Arg-1 protein expression was lower in the hypertension group(all P<0.05). Additionally, TREM2 and IGF-1 protein expression in the hypertension and DPM groups were lower than those in the control group but higher than those in the hypertension+ DPM group(all P<0.05).(3)The protein expressions of IL-1β, IL-6 and TNF-α in BV2 cells of the DPM+ AngⅡ-TREM2 overexpression group were lower than those of the DPM+ AngⅡ group. The expression of iNOS was lower than that in the DPM+ AngⅡ group, while the expression of Arg-1 was higher than that in the DPM+ AngⅡ group(all P<0.05). Conclusion:DPM exposure aggravates anxious- and depressive-like behaviors in hypertensive model mice, with TREM2/IGF-1-regulated microglial polarization playing a significant role in this process.
