Fluoxetine improves depression-like behavior in CUMS rats by regulating TLR4/NF-κB/NLRP3 inflammasome signaling pathway

doi:10.11958/20220674

Abstract

Abstract:

Objective To investigate the effects of fluoxetine on depression-like behavior in chronic unpredictable mild stress (CUMS) model rats based on Toll-like receptor 4 (TLR4) /nuclear factor κB (NF-κB)/NOD-like receptor pyrin domain-associated protein 3 (NLRP3) inflammasome signaling pathway. Methods Eighteen SD rats were randomly divided into the control group, the model group and the fluoxetine group. Rats in the model group and the fluoxetine group were randomly given CUMS for 11 weeks to establish depression model. The fluoxetine group was treated with fluoxetine (10 mg·kg^-1·d^-1) through gastric perfusion from the 7th to the 11th week, and the other groups were given 1 mL of normal saline by gavage. Behavioral tests were conducted after the intervention. The levels of interleukin (IL)-1β and IL-18 in brain tissue were tested by enzyme-linked immunosorbent assay (ELISA). The expression of NLRP3 protein, apoptosis-associated speck-like protein (ASC) and cysteine aspartate protease 1 (Caspase-1) protein in hippocampal CA3 area and cortical area regions were observed by immunofluorescence staining. Western blot assay was used to detect the protein expression levels of TLR4, NF-κB, NLRP3, Caspase-1 and activated cysteine aspartate protease 1 (cleaved Caspase-1) in brain tissue. Results Compared with the model group, the movement distance and standing times of rats in open field test were significantly increased, the movement distance in the elevated plus maze test was increased, and the dwell time in closed arms was decreased in the fluoxetine group. The contents of IL-1β and IL-18 in brain tissue were significantly decreased, and expression levels of TLR4, NF-κB, NLRP3, ASC, Caspase-1 and cleaved Caspase-1 proteins were also down-regulated in the fluoxetine group than those of the model group (P<0.05). Conclusion Fluoxetine may improve depression-like behavior in CUMS rats by inhibiting TLR4/NF-κB/NLRP3 inflammasome signaling pathway and reducing the levels of inflammatory factors IL-1β and IL-18 in brain tissue.

Key words: depressive disorder, fluoxetine, Toll-like receptor 4, NF-kappa B, NLR family, pyrin domain-containing 3 protein, interleukin-1beta, interleukin-18, caspase 1, ASC

CLC Number:

R749.42

Figures/Tables 6

References 19

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组别	旷场实验		高架十字迷宫实验
组别	总运动距离（m）	站立次数	总运动距离（m）	闭臂停留时间（s）
对照组	12.14±3.89	10.67±4.84	8.24±1.79	237.98±7.32
模型组	3.75±2.25^a	3.17±3.12^a	2.21±1.18^a	284.32±7.99^a
氟西汀组	10.66±2.12^b	10.67±3.39^b	7.96±1.62^b	208.38±27.41^b
F	14.555^＊＊	7.550^＊＊	28.763^＊＊	30.342^＊＊

组别	旷场实验		高架十字迷宫实验
组别	总运动距离（m）	站立次数	总运动距离（m）	闭臂停留时间（s）
对照组	12.14±3.89	10.67±4.84	8.24±1.79	237.98±7.32
模型组	3.75±2.25^a	3.17±3.12^a	2.21±1.18^a	284.32±7.99^a
氟西汀组	10.66±2.12^b	10.67±3.39^b	7.96±1.62^b	208.38±27.41^b
F	14.555^＊＊	7.550^＊＊	28.763^＊＊	30.342^＊＊

组别	TLR4	NF-κB	cleaved Caspase-1	NLRP3	Caspase-1
对照组	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
模型组	1.42±0.27^a	1.44±0.33^a	1.36±0.14^a	1.28±0.28^a	1.42±0.14^a
氟西汀组	1.12±0.21^b	0.97±0.19^b	1.06±0.17^b	0.97±0.25^b	1.07±0.17^b
F	16.689^＊＊	16.095^＊＊	28.289^＊＊	16.172^＊＊	34.212^＊＊

组别	TLR4	NF-κB	cleaved Caspase-1	NLRP3	Caspase-1
对照组	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00	1.00±0.00
模型组	1.42±0.27^a	1.44±0.33^a	1.36±0.14^a	1.28±0.28^a	1.42±0.14^a
氟西汀组	1.12±0.21^b	0.97±0.19^b	1.06±0.17^b	0.97±0.25^b	1.07±0.17^b
F	16.689^＊＊	16.095^＊＊	28.289^＊＊	16.172^＊＊	34.212^＊＊