Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain

Gong, Yu; Chai, Yi; Ding, Jingzhong; Sun, Xiu‐Lan; Hu, Gang

doi:10.1016/j.neulet.2010.11.006

Cited by 153 publications

(94 citation statements)

References 30 publications

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“…Consistent with our findings, complex III, which is the other principal source of mitochondrial ROS, did not show a change in activity (34). Chronic stress has been shown to produce results similar to the effects of high-dose corticosteroids on mitochondrial function in intact rodent brains (35)(36)(37), suggesting that the transcriptional activity of GR in brain mitochondria is a consistent mechanism for the transduction of psychological stress into molecular pathology. Mitochondrial dysfunction in general, and complex I deficits specifically, have been shown to be associated with a number of neurodegenerative and neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, and bipolar disorder (38)(39)(40).…”

Section: Discussionsupporting

confidence: 89%

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Hunter

Seligsohn

Rubin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

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Glucocorticoids (GCs) are involved in stress and circadian regulation, and produce many actions via the GC receptor (GR), which is classically understood to function as a nuclear transcription factor. However, the nuclear genome is not the only genome in eukaryotic cells. The mitochondria also contain a small circular genome, the mitochondrial DNA (mtDNA), that encodes 13 polypeptides. Recent work has established that, in the brain and other systems, the GR is translocated from the cytosol to the mitochondria and that stress and corticosteroids have a direct influence on mtDNA transcription and mitochondrial physiology. To determine if stress affects mitochondrially transcribed mRNA (mtRNA) expression, we exposed adult male rats to both acute and chronic immobilization stress and examined mtRNA expression using quantitative RT-PCR. We found that acute stress had a main effect on mtRNA expression and that expression of NADH dehydrogenase 1, 3, and 6 (ND-1, ND-3, ND-6) and ATP synthase 6 (ATP-6) genes was significantly down-regulated. Chronic stress induced a significant up-regulation of ND-6 expression. Adrenalectomy abolished acute stress-induced mtRNA regulation, demonstrating GC dependence. ChIP sequencing of GR showed that corticosterone treatment induced a dose-dependent association of the GR with the control region of the mitochondrial genome. These findings demonstrate GR and stress-dependent transcriptional regulation of the mitochondrial genome in vivo and are consistent with previous work linking stress and GCs with changes in the function of brain mitochondria.nuclear receptors | allostasis | mitochondrial plasticity | brain metabolism | mitochondrial transcription

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Section: Discussionsupporting

confidence: 89%

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Hunter

Seligsohn

Rubin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

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“…Rats increase their body weight until about 18 months of age ( Sengupta et al 2005). Therefore, many authors refer to this effect as a reduction of body weight gain, because they use young animals (Marin et al 2007, Garcia et al 2009, Gong et al 2011). However, not all researchers observe weight loss or reduction of body weight gain in rats submitted to CMS (Bekris et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Effects of chronic mild stress on parameters of bone assessment in adult male and female rats

et al. 2016

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RESUMO.-[Efeito do estresse moderado crônico sobre parâmetros de avaliação óssea em ratos adultos machos e fêmeas.] A osteoporose é uma doença multifatorial, de alta prevalência e que tem um grande impacto na qualidade de vida, principalmente porque os efeitos sobre a estrutura do osso aumentam o risco de fraturas, que podem ser muito debilitantes. Com base na observação de que pacientes com depressão têm menor densidade mineral óssea que indivíduos saudáveis , muitos estudos têm indicado que o estresse pode ser um fator agravante para a perda óssea. Este estudo avalia o efeito de um protocolo de estresse moderado crônico (EMC) em parâmetros de avaliação óssea em ratos machos e fêmeas. Cinco animais de cada sexo, com cinco meses de idade, foram submetidos a um cronograma de aplicação de estressores durante 28 dias. Os estressores incluídos foram: frio, calor, contenção, inclinação da gaiola, isolamento, iluminação durante a noite e privação de água e ração. Cinco animais de cada sexo foram mantidos com um Osteoporosis is a multifactorial disease of high prevalence and has great impact on quality of life, because the effects on bone structure increase the risk of fractures, what may be very debilitating. Based on the observation that patients with depression have lower bone mineral density than healthy individuals, many studies have indicated that stress could be an aggravating factor for bone loss. This study evaluates the effect of a protocol of chronic mild stress (CMS) on parameters of bone assessment in male and female rats. Five 5-monh--old rats of each sex underwent a schedule of stressor application for 28 days. Stressors included cold, heat, restraint, cage tilt, isolation, overnight illumination, and water and food deprivation. Five rats of each sex were kept under minimum intervention as control group. The animals were weighed at beginning and end of the period, and after euthanasia had their bones harvested. Femur, tibia and lumbar vertebrae were analyzed by bone densitometry. Biomechanical tests were performed in femoral head and diaphysis. Trabecular bone volume was obtained from histomorphometric analysis of femoral head and vertebral body, as well as of femoral midshaft cross-sectional measures. Not all parameters analyzed showed effect of CMS. However, tibial and L4 vertebral bone mineral density and cross--sectional cortical/medullar ratio of femoral shaft were lower in female rats submitted to the CMS protocol. Among male rats, the differences were significant for femoral trabecular bone volume and maximum load obtained by biomechanical test. Thus, it could be confirmed that CMS can affect the balance of bone homeostasis in rats, what may contribute to the establishment of osteopenia or osteoporosis. Effects of chronic mild stress on parameters of bone assessment in adult male and female rats mínimo de intervenção como grupo controle. Os animais foram pesador no início e no final do período, e após eutanásia tiveram seus ossos coletados. Fêmur, tíbia e vértebra lombar foram analisados por dens...

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“…75 Rezin et al 76 reported that mitochondrial respiratory chain complexes I, III and IV were inhibited in the cerebral cortex and cerebellum of rats after 40 days of chronic mild stress (CMS), and this was reversed by administration of ketamine. 77 Gong et al 78 showed that exposure to CMS inhibited mitochondrial respiration and dissipated mitochondrial membrane potential. In addition, the mitochondrial ultrastructure was altered in brains of mice exposed to CMS.…”

Section: Depressionmentioning

confidence: 99%

“…In addition, the mitochondrial ultrastructure was altered in brains of mice exposed to CMS. 78 Genetic evidence points to a role for mitochondrial impairment in depression. Postmortem brain tissue from a patient with severe depression was found to have more mtDNA deletions than postmortem muscle tissues from the same patient, suggesting that the accumulation of mtDNA deletions in the brain might play a role in the pathophysiology of depression.…”

Section: Depressionmentioning

confidence: 99%

Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

Streck

Gonçalves

Furlanetto

et al. 2014

Rev. Bras. Psiquiatr.

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Introduction: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. Methodology: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessivecompulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. Results: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. Conclusions: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects.

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Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain

Cited by 153 publications

References 30 publications

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor

Effects of chronic mild stress on parameters of bone assessment in adult male and female rats

Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

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