PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed nice

Objective To determine the effects and underlying mechanism of pterostilbene (PTE) on memory dysfunction in mice exposed to chronic unpredictable military stress (CUMS). Methods Thirty-six healthy 7 to 8 week-old C57BL/6J male mice were randomly divided into control group (CON), CUMS group (for 30 d...

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Main Authors: CHANG Mengyun, CHEN Ka, LI Yue, ZHANG Jun, LI Tianyou
Format: Article
Language:zho
Published: Editorial Office of Journal of Army Medical University 2023-06-01
Series:陆军军医大学学报
Subjects:
Online Access:http://aammt.tmmu.edu.cn/html/202209149.htm
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author CHANG Mengyun
CHEN Ka
LI Yue
ZHANG Jun
LI Tianyou
author_facet CHANG Mengyun
CHEN Ka
LI Yue
ZHANG Jun
LI Tianyou
author_sort CHANG Mengyun
collection DOAJ
description Objective To determine the effects and underlying mechanism of pterostilbene (PTE) on memory dysfunction in mice exposed to chronic unpredictable military stress (CUMS). Methods Thirty-six healthy 7 to 8 week-old C57BL/6J male mice were randomly divided into control group (CON), CUMS group (for 30 d) and PTE intervention group (100 mg/kg PTE, gastric infusion). Body weight and food intake of each mouse were recorded during the intervention. After the intervention, serum corticosterone concentrations were detected by ELISA, spatial memory function of mouse was detected by Morris water maze assay, ultrastructural changes of mice hippocampal neurons were observed by transmission electron microscopy, mitochondrial respiratory function of mouse hippocampus was detected by Seahorse XF HS Mini analyzer, the relative copy number of mtDNA and the expression of Pgc-1α and Tfam at mRNA level in the hippocampus were detected by RT-qPCR, and the protein level of PGC-1α was measured with Western blotting. Results Compared with the CON group, the CUMS group had significantly decreased body weight and food intake (P < 0.05), increased serum content of corticosterone (P < 0.000 1), while PTE intervention reversed above changes (P < 0.05 and P < 0.000 1, respectively). Morris water maze assay showed that the CUMS group were worse in the memory accuracy of the platform, while the PTE group had better performance. After exposure to CUMS, more lipofuscin, swollen mitochondria and disappearance of cristae were observed with transmission electron microscopy, but comparatively mild damages were found in the PTE group. Moreover, mitochondrial basal respiration (P < 0.05), maximal respiration (P < 0.001) and spare respiratory capacity (P < 0.01) in isolated hippocampal neurons were decreased after exposed to CUMS, whereas the maximal respiration (P < 0.05), ATP-linked respiration (P < 0.05) and respiratory control rate (P < 0.05) were significantly improved in the PTE group. Furthermore, the copy number of mtDNA (P < 0.01), and the expression of Pgc-1α (P < 0.000 1) and Tfam (P < 0.01) at mRNA level in the hippocampus of the CUMS group were decreased; while those phenomena were significantly elevated in the CUMS group (P < 0.05). Western blotting indicated the expression of PGC-1α was lower in the hippocampus of the CUMS group than the CON group (P < 0.01), whereas that was significantly higher in the PTE group than the CUMS group (P < 0.05). Conclusion PTE could improve the memory function of CUMS-exposed mice, which might be related with its enhancing PGC-1α expression and thus mitigating the CUMS-induced structural and functional damages in the hippocampal mitochondria.
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spelling doaj.art-443db822738d4429ace2f313f880f3b42023-06-14T00:08:47ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272023-06-0145111121113010.16016/j.2097-0927.202209149PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed niceCHANG Mengyun0CHEN Ka1 LI Yue2ZHANG Jun3LI Tianyou4Research Center for Military Nutrition and Food Safety, Chongqing Research Center for Medical Nutrition, Chongqing Key Laboratory of Nutrition and Food Safety, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaResearch Center for Military Nutrition and Food Safety, Chongqing Research Center for Medical Nutrition, Chongqing Key Laboratory of Nutrition and Food Safety, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaResearch Center for Military Nutrition and Food Safety, Chongqing Research Center for Medical Nutrition, Chongqing Key Laboratory of Nutrition and Food Safety, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaResearch Center for Military Nutrition and Food Safety, Chongqing Research Center for Medical Nutrition, Chongqing Key Laboratory of Nutrition and Food Safety, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaResearch Center for Military Nutrition and Food Safety, Chongqing Research Center for Medical Nutrition, Chongqing Key Laboratory of Nutrition and Food Safety, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, ChinaObjective To determine the effects and underlying mechanism of pterostilbene (PTE) on memory dysfunction in mice exposed to chronic unpredictable military stress (CUMS). Methods Thirty-six healthy 7 to 8 week-old C57BL/6J male mice were randomly divided into control group (CON), CUMS group (for 30 d) and PTE intervention group (100 mg/kg PTE, gastric infusion). Body weight and food intake of each mouse were recorded during the intervention. After the intervention, serum corticosterone concentrations were detected by ELISA, spatial memory function of mouse was detected by Morris water maze assay, ultrastructural changes of mice hippocampal neurons were observed by transmission electron microscopy, mitochondrial respiratory function of mouse hippocampus was detected by Seahorse XF HS Mini analyzer, the relative copy number of mtDNA and the expression of Pgc-1α and Tfam at mRNA level in the hippocampus were detected by RT-qPCR, and the protein level of PGC-1α was measured with Western blotting. Results Compared with the CON group, the CUMS group had significantly decreased body weight and food intake (P < 0.05), increased serum content of corticosterone (P < 0.000 1), while PTE intervention reversed above changes (P < 0.05 and P < 0.000 1, respectively). Morris water maze assay showed that the CUMS group were worse in the memory accuracy of the platform, while the PTE group had better performance. After exposure to CUMS, more lipofuscin, swollen mitochondria and disappearance of cristae were observed with transmission electron microscopy, but comparatively mild damages were found in the PTE group. Moreover, mitochondrial basal respiration (P < 0.05), maximal respiration (P < 0.001) and spare respiratory capacity (P < 0.01) in isolated hippocampal neurons were decreased after exposed to CUMS, whereas the maximal respiration (P < 0.05), ATP-linked respiration (P < 0.05) and respiratory control rate (P < 0.05) were significantly improved in the PTE group. Furthermore, the copy number of mtDNA (P < 0.01), and the expression of Pgc-1α (P < 0.000 1) and Tfam (P < 0.01) at mRNA level in the hippocampus of the CUMS group were decreased; while those phenomena were significantly elevated in the CUMS group (P < 0.05). Western blotting indicated the expression of PGC-1α was lower in the hippocampus of the CUMS group than the CON group (P < 0.01), whereas that was significantly higher in the PTE group than the CUMS group (P < 0.05). Conclusion PTE could improve the memory function of CUMS-exposed mice, which might be related with its enhancing PGC-1α expression and thus mitigating the CUMS-induced structural and functional damages in the hippocampal mitochondria. http://aammt.tmmu.edu.cn/html/202209149.htmpterostilbenechronic unpredictable military stressmemorymitochondriapgc-1α
spellingShingle CHANG Mengyun
CHEN Ka
LI Yue
ZHANG Jun
LI Tianyou
PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed nice
陆军军医大学学报
pterostilbene
chronic unpredictable military stress
memory
mitochondria
pgc-1α
title PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed nice
title_full PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed nice
title_fullStr PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed nice
title_full_unstemmed PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed nice
title_short PGC1-α mediated regulatory effect on mitochondrial function of PTE mitigating memory impairment in chronic unpredictable military stress exposed nice
title_sort pgc1 α mediated regulatory effect on mitochondrial function of pte mitigating memory impairment in chronic unpredictable military stress exposed nice
topic pterostilbene
chronic unpredictable military stress
memory
mitochondria
pgc-1α
url http://aammt.tmmu.edu.cn/html/202209149.htm
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