Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway

Wu, Yanqin; Sun, Fengying; Guo, Yujin; Zhang, Yumao; Li, Li; Dang, Ruili; Jiang, Pei

doi:10.1155/2021/2630445

Cited by 22 publications

(18 citation statements)

References 48 publications

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“…Intriguingly, inducing a depressive-like state by deprivation of social interaction had no impact on fndc5 expression in neither region. It is noteworthy that previous reports have indicated that chronic unpredictable stress protocols reduce hippocampal fndc5 expression in mice (Babaei et al, 2021;Wu et al, 2021).…”

Section: Discussionmentioning

confidence: 86%

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Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression

Lima-Filho

Fortuna

Cozachenco

et al. 2023

eNeuro

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Major depressive disorder (MDD) is a major cause of disability in adults. MDD is both a co-morbidity and a risk factor for Alzheimer’s disease (AD), and regular physical exercise has been associated with reduced incidence and severity of MDD and AD. Irisin is an exercise-induced myokine derived from proteolytic processing of fibronectin type III domain-containing protein 5 (FNDC5). FNDC5/irisin is reduced in the brains of AD patients and mouse models. However, whether brain FNDC5/irisin expression is altered in depression remains elusive. Here, we investigate changes infndc5expression in post-mortem brain tissue from MDD individuals and mouse models of depression. We found decreasedfndc5expression in the MDD prefrontal cortex, both with and without psychotic traits. We further demonstrate that induction of depressive-like behavior in male mice by lipopolysaccharide decreasedfndc5expression in the frontal cortex, but not in the hippocampus. Conversely, chronic corticosterone administration increasedfndc5expression in the frontal cortex, but not in the hippocampus. Social isolation in mice did not result in alteredfndc5expression in either frontal cortex or hippocampus. Finally, fluoxetine, but not other antidepressants, increasedfndc5gene expression in the mouse frontal cortex. Results indicate a region-specific modulation offndc5in depressive-like behavior and by antidepressant in mice. Our finding of decreased prefrontal cortexfndc5expression in MDD individuals differs from results in mice, highlighting the importance of carefully interpreting observations in mice. The reduction infndc5mRNA suggests that decreased central FNDC5/irisin could comprise a shared pathological mechanism between MDD and AD.Significance StatementMajor depressive disorder (MDD) is a major cause of disability in humans. Physical exercise reduces the incidence and severity of MDD, but molecular mechanisms are elusive. One of the pleiotropic actions of exercise alludes to the increased production and circulation of irisin, a myokine cleaved from fibronectin type III domain-containing protein 5 (FNDC5) that mediates some benefits of exercise in the brain. Here, we observed reducedfndc5expression in post-mortem samples of dorsolateral prefrontal cortex from patients with MDD. In the mouse frontal cortex, modulation offndc5was variable across models of depressive-like behavior. Our findings indicate reducedfndc5expression in MDD with discordant results in mice and stimulate further research on the roles of brain FNDC5/irisin in MDD.

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Section: Discussionmentioning

confidence: 86%

“…In rodents, a chronic unpredictable stress protocol reduced levels of FNDC5/irisin in the hippocampus ( Babaei et al, 2021 ; Wu et al, 2021 ). In addition, intracerebroventricular administration of irisin (0.5–1 ng) reduced immobility times in the tail suspension and forced swim tests in mice ( Siteneski et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression

Lima-Filho

Fortuna

Cozachenco

et al. 2023

eNeuro

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“…The doses of each treatment used in this study were according to the previous reports. 15,19,20 Briefly, the mice of the CON group were subjected to intraperitoneal injections with the same volume of PBS and oral gavage. The CORT group was given a corticosterone injection intraperitoneally (40 mg/kg/day) and a PBS gavage.…”

Section: Animalsmentioning

confidence: 99%

“…PGC‐1α is crucial for preventing neuronal death, as evidenced by research in animals 14 . Our previous investigations have discovered that hippocampal PGC‐1α levels tend to reduce in rats experiencing chronic unpredictable mild stress (CUMS) 15 . It has recently been reported that PGC‐1α mRNA levels in whole blood are lower in depressed patients compared to healthy controls 16 …”

Section: Introductionmentioning

confidence: 99%

“…14 Our previous investigations have discovered that hippocampal PGC-1α levels tend to reduce in rats experiencing chronic unpredictable mild stress (CUMS). 15 It has recently been reported that PGC-1α mRNA levels in whole blood are lower in depressed patients compared to healthy controls. 16 Curcumin (CUR) is a naturally occurring polyphenol compound with a range of pharmacological benefits, such as reducing oxidative stress, mitigating inflammation and promoting healthy neuronal function.…”

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confidence: 99%

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Curcumin relieves corticosterone‐induced behaviour deficits via PGC‐1α‐mediated mitochondrial biogenesis and mitophagy

Zhang

Guo

et al. 2022

Clinical and Translational Dis

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Curcumin (CUR), an FDA‐approved natural product, has been found to be clinically effective in treating depression. However, the underlying mechanism remains elusive. PGC‐1α is a key factor in regulating mitochondrial health and depression. This study randomly divided C57BL/6 mice or cultured hippocampal neurons into four groups: CON, CORT, CORT + CUR and CORT + CUR + SR18292. The present study demonstrated that CUR was effective in suppressing CORT‐induced depressive‐like behaviour, as well as improving anxiety‐like behaviour and cognitive function. CUR was found to be effective in preventing oxidative stress induced by corticosterone (CORT), as evidenced by the restoration of Nrf2, NQO‐1, HO‐1, GCLC, SOD‐1 and DHE levels in cells. CUR inhibited the CORT‐induced perinuclear accumulation of mitochondria in vitro. Furthermore, CUR promoted mitochondrial biogenesis, potentially reversing the effect of CORT on NRF1, TFAM, PGC‐1α and the relative MT‐CO1/SDH‐A ratio. Lastly, the treatment of CUR normalized the CORT‐hindered mitophagy by upregulating the protein level of NIX, Beclin‐1, PINK1, Parkin and LC3II/LC3I, and enhancing the relative mt‐Keima signal. The protective effect of CUR was entirely negated by SR18292. CUR could regulate oxidative stress, mitochondrial biogenesis and mitophagy via PGC‐1α to achieve an anti‐depressive‐like function. This study would contribute to a greater understanding of how CUR alleviates depressive symptoms.

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Impact of Curcumin on Aging: Its Manifestations and Limitations

Banji,

Banji

2023

Curcumin and Neurodegenerative Diseases

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Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway

Cited by 22 publications

References 48 publications

Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression

Brain FNDC5/Irisin Expression in Patients and Mouse Models of Major Depression

Curcumin relieves corticosterone‐induced behaviour deficits via PGC‐1α‐mediated mitochondrial biogenesis and mitophagy

Impact of Curcumin on Aging: Its Manifestations and Limitations

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