Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway

doi:10.12122/j.issn.1673-4254.2024.05.02

Abstract

Abstract:

Objective To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress (CRS). Methods Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low, moderate and high doses (50, 100 and 200 mg/kg, respectively, n=8), VX765 (a caspase-1 specific inhibitor, 50 mg/kg, n=8), or fluoxetine (10 mg/kg, n=8) on a daily basis for 4 weeks, and the changes in depression-like behaviors of the mice were assessed by sugar water preference test, forced swimming test and tail suspension test. The expression of glial fibrillary acidic protein (GFAP) in the hippocampus of the mice was detected using immunohistochemistry, and the number of synaptic spines was determined with Golgi staining. Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus, and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay. Results Compared with the normal control mice, the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests (P<0.05), and these depression-like behaviors were obviously improved by treatment with coenzyme Q10, VX765 or FLX. The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines, enhanced expressions of GSDMD-N, caspase-1 and IL-1β, and increased colocalization of neurons and caspase-1 p10 (all P<0.05). All these changes were significantly ameliorated in the mouse models after treatment with Q10. Conclusion Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

Key words: chronic restraint stress, depression, coenzyme Q10, caspase-1, pyroptosis

Yiming SUN, Rong ZHANG, Ying MENG, Lei ZHU, Mingqiang LI, Zhe LIU. Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway[J]. Journal of Southern Medical University, 2024, 44(5): 810-817.

Figures/Tables 4

Fig.2 Coenzyme Q10 alleviates the loss of astrocytes in the hippocampus of mice with CRS (Original magnification: ×200). A, B: Immunohistochemistry and positive rate of GFAP in the hippocampus. C, D: Results of Western blotting for detecting GFAP protein expression. *P<0.05 vs CON, #P<0.05 vs CRS.

Fig. 3 Coenzyme Q10 reduces the loss of synaptic spines in the hippocampus of CRS mice (Golgi staining, scale bar=10 μm). ***P <0.001 vs CON; #P <0.05, ##P <0.01 vs CRS.

Fig.4 Coenzyme Q10 reduces expressions of pyroptosis-related proteins in the hippocampus of CRS mice detected by Western blotting. *P<0.05, **P<0.01 vs CON; #P<0.05, ##P<0.01 vs CRS.

Fig.5 Coenzyme Q10 reduces colabeling of caspase-1 p10 and hippocampal neurons in CRS mice. A: Immunofluorescence staining of the hippocampal neurons. B: Number of colocalization of neurons and caspase-1 p10. ***P<0.001 vs CON; ###P<0.001 vs CRS.

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