Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression

Rezin, Gislaine T.; Cardoso, Mariane R.; Gonçalves, Cinara L.; Scaini, Giselli; Fraga, Daiane B.; Riegel, Rafael E.; Comim, Clarissa M.; Quevedo, Joao L De; Streck, Emílio L.

doi:10.1016/j.neuint.2008.09.012

Cited by 182 publications

(119 citation statements)

References 58 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: 88%

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: 88%

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

View full text Add to dashboard Cite

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“…Genetic studies have shown that decreased mitochondrial DNA transcription and mitochondrial diseases are highly correlated to MDD (Fattal et al, 2006;Shao et al, 2008). In chronic stress animal models of depression, the activities of complex I, II, III and IV in mitochondrial electron-transport chain were inhibited after 21 days and 40 days of stress (Madrigal et al, 2001;Rezin et al, 2008). The complexes I, III and IV were only inhibited in the cerebral cortex and cerebellum (Rezin et al, 2008), where structural abnormalities have also been found in patients with mood disorders (Konarski et al, 2008).…”

Section: Dysfunction-related Oligodendrocyte Malfunction In Mddmentioning

confidence: 99%

Hyperforin promotes mitochondrial function and development of oligodendrocytes

Wang

Zhang

et al. 2011

Journal of Neurochemistry

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Major depressive disorder is a common severe psychiatric disorder with unknown etiology. Recent studies show that the loss and malfunction of oligodendrocytes are closely related to the neuropathological changes in depression, which can be reversed by antidepressant treatment. St. John's wort is an effective and safe herbal treatment for depression in several clinical trials. However, the underlying mechanism of its therapeutic effects is unclear. In this study, we evaluated the effects of hyperforin, a iii ACKNOWLEDGEMENTS

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“…48 We have also recently demonstrated that mitochondrial respiratory chain is inhibited in brain of rats after chronic variable stress (40 days), suggesting that energy metabolism impairment may occur in depressive disorders. 51 Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in CK activity) by antidepressants could be an important mechanism of action of these drugs. Further studies are currently being carried out in order to evaluate whether other enzymes involved in metabolism are also affected by antidepressants, especially ketamine.…”

Section: Discussionmentioning

confidence: 99%

Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats

Assis

Rezin

Comim

et al. 2009

Rev. Bras. Psiquiatr.

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Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression

Cited by 182 publications

References 58 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

Hyperforin promotes mitochondrial function and development of oligodendrocytes

Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats

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