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Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression
Abstract
Depressive disorders, including major depression, are serious and disabling. However, the exact pathophysiology of depression is not clearly understood. Life stressors contribute in some fashion to depression and are an extension of what occurs normally. In this context, chronic stress has been used as an animal model of depression. Based on the hypothesis that metabolism impairment might be involved in the pathophysiology of depression, in the present work we evaluated the activities of mitochondrial respiratory chain complexes and creatine kinase in brain of rats subjected to chronic stress. After 40 days of mild stress, a reduction in sweet food ingestion was observed, as well as increased adrenal gland weight, when compared to control group. We also verified that control group gained weight after 40 days, but stressed group did not. Moreover, our findings showed that complex I, III and IV were inhibited in stress group only in cerebral cortex and cerebellum. On the other hand, complex II and creatine kinase were not affected in stressed group. Although it is difficult to extrapolate our findings to the human condition, the inhibition of mitochondrial respiratory chain by chronic stress may be one mechanism in the pathophysiology of depressive disorders.
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“Preclinical models of MDD suppress mitochondrial function223.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [223]
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InfluentialMitochondrial transplantation attenuates lipopolysaccharide- induced depression-like behaviors
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“In chronic stress animal models of depression, there is inhibition of activity in several of the complexes located in the mitochondrial respiratory chain in rat brain [12,13].”
BackgroundProtein biomarkers of susceptibility and resilience to stress in a rat model of depression
Palmfeldt, J., Henningsen, K., Eriksen, S. A., Müller, H. K., & Wiborg, O. (2016) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2016.04.001 · Cited by 53
Tagliari, B., Noschang, C. G., Ferreira, A. G. K., Ferrari, O. A., Feksa, L. R., Wannmacher, C. M. D., Dalmaz, C., & Wyse, Â. T. D. S. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9194-x · Cited by 50
“However, the causes and consequences of this reduction seem to be different in each brain region, as demonstrated in several studies that presented region-specific alterations in rats (Vasconcellos et al. 2006; Rezin et al. 2008; Ni et al. 2008).”
BackgroundChoi, W., Kim, H.-W., Tronche, F., Palmiter, R. D., Storm, D. R., & Xia, Z. (2017) · Scientific Reports · doi:10.1038/srep44989 · Cited by 49
Menezes, I. C., Baes, C. V. W., Lacchini, R., & Juruena, M. F. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.01.008 · Cited by 47
Perić, I., Costina, V., Stanisavljević, A., Findeisen, P., & Filipović, D. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.03.034 · Cited by 46
Emmerzaal, T. L., Preston, G. J., Geenen, B., Verweij, V., Wiesmann, M., Vasileiou, E., Grüter, F., de Groot, C., Schoorl, J., de Veer, R., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0858-y · Cited by 51
Kahl, K. G., Stapel, B., & Frieling, H. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.09.004 · Cited by 47
“An animal model of depression showed that chronic mild stress inhibits complexes from the electron transport chain in the cerebellum and cortex (Rezin et al., 2008).”
Methylene blue and its analogues as antidepressant compounds
Delport, A., Harvey, B. H., Petzer, A., & Petzer, J. P. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0081-6 · Cited by 46
“IV in the cerebellum and cortex have also been found to be impaired (Rezin et al. 2008).”
BackgroundRappeneau, V., Wilmes, L., & Touma, C. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103555 · Cited by 47
Neuroinflammation and Mitochondrial Dysfunction Link Social Stress to Depression
Hollis, F., Pope, B. S., Gorman‐Sandler, E., & Wood, S. K. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2021_300 · Cited by 47
Psychosocial experiences are associated with human brain mitochondrial biology
Trumpff, C., Monzel, A. S., Sandi, C., Menon, V., Klein, H., Fujita, M., Lee, A., Petyuk, V., Hurst, C. D., Duong, D. M., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2317673121 · Cited by 46
“In animals, chronic stress leads to reduced protein expression specifically of complex I (87), complex I enzymatic activity (25, 88–91), and complex I–driven respiration (24).”
BackgroundLiu, Y., Yang, N., Hao, W., Zhao, Q., Ying, T., Liu, S., Li, Q., Liang, Y., Wang, T., Dong, Y., et al. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.02.019 · Cited by 46
“Our results were consistent with other studies have been performed to investigate the mitochondrial dysfunction in depression (Gardner et al., 2003; Gamaro et al., 2003; Rezin et al., 2008; Madrigal et al., 2001).”
Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism
Głombik, K., Detka, J., Kurek, A., & Budziszewska, B. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.586939 · Cited by 45
Mallei, A., Giambelli, R., Gass, P., Racagni, G., Mathé, A. A., Vollmayr, B., & Popoli, M. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.12.012 · Cited by 44
Wang, Q., & Dwivedi, Y. (2016) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2016.1197423 · Cited by 43
“For example, chronic stress-induced depression in rodents leads to inhibition of the mitochondrial respiratory chain in the cortex and cerebellum (Rezin et al. 2008).”
BackgroundKolář, D., Kletečková, L., Brožka, H., & Valeš, K. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.136003 · Cited by 46
Harro, J., Kanarik, M., Matrov, D., & Panksepp, J. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.02.016 · Cited by 45
Sex-dependent mental illnesses and mitochondria
Shimamoto, A., & Rappeneau, V. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.02.025 · Cited by 42
“Also, an inhibition of the mitochondrial respiratory chain was observed in animals that were exposed to chronic stress (Rezin et al., 2008).”
BackgroundExploring the mechanisms of action of the antidepressant effect of the ketogenic diet
Ricci, A. L., Idzikowski, M. A., Soares, C. N., & Brietzke, E. M. (2020) · Reviews in the Neurosciences · doi:10.1515/revneuro-2019-0073 · Cited by 44
Pope, B. S., & Wood, S. K. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.06.031 · Cited by 44
“For example, chronic mild stress and chronic immobilization stress reduce the activity of the mitochondrial respiratory chain complexes within the rat brain cortex (Madrigal et al., 2001; Rezin et al., 2008) and reduced Na+, K+-ATPase activity in the hippocampus (Gamaro et al.”
BackgroundRéus, G. Z., Stringari, R. B., Gonçalves, C. L., Scaini, G., Carvalho‐Silva, M., Jeremias, G. C., Jeremias, I. C., Ferreira, G. K., STRECK, E. L., Hallak, J. E. C., et al. (2011) · Depression Research and Treatment · doi:10.1155/2012/987397 · Cited by 43
“genesis of a range of psychiatric disorders [26–28], including”
BackgroundSelf-citationDella, F. P., Abelaira, H. M., Réus, G. Z., dos Santos, M. A. B., Tomaz, D. B., Antunes, A. R., Scaini, G., Morais, M. O. D. S., STRECK, E. L., & Quevedo, J. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-012-9375-x · Cited by 41
“A study from our group showed that mitochondrial respiratory chain complexes I, III and IV were inhibited in the cerebral cortex and cerebellum after chronic mild stress, and that the acute administration of ketamine reversed this inhibition (Rezin et al. 2008).”
Self-citationThe possible beneficial effects of creatine for the management of depression
Pazini, F. L., Cunha, M. P., & Rodrigues, A. L. S. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.08.029 · Cited by 47
“fected in rats submitted to 40 days of mild stress (Rezin et al., 2008).”
Mitochondria could be a potential key mediator linking the intestinal microbiota to depression
Chen, J., & Vitetta, L. (2020) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29311 · Cited by 36
Hendawy, N., Salaheldin, T. H., & Abuelezz, S. A. (2023) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-023-10060-3 · Cited by 38
Mitochondrial DNA copy number, damage, repair and degradation in depressive disorder
Czarny, P. L., Wigner, P., Strycharz, J., Świderska, E., Synowiec, E., Szatkowska, M., Śliwińska, A., Talarowska, M. E., Szemraj, J., Su, K., et al. (2019) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2019.1588993 · Cited by 38
“In addition, studies conducted on rats subjected to chronic stress (including chronic mild stress model of depression) showed an inhibition of complex I, III and IV of ETC in their cerebral cortex and cerebellum (Rezin et al. 2008).”
BackgroundAboul‐Fotouh, S. (2013) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3283654029 · Cited by 37
“However, despite the fact that depression in humans and in animal models did not alter brain CK activity (Rezin et al., 2008; Forester et al., 2012), similar to the present results, chronic administration of some antidepressants, such as imipramine and paroxetine, increased CK activity in rat brain (Santos et al.”
BackgroundResultUNIVERSIDADE DO EXTREMO SUL CATARINENSE - UNESC
Saúde, U. A. D., & Rosa, J. L. N. D. (2011) · Cited by 36
Effect of neuropsychiatric medications on mitochondrial function: For better or for worse
Emmerzaal, T. L., Nijkamp, G., Veldić, M., Rahman, S., Andreazza, A. C., Morava, É., Rodenburg, R. J., & Kozicz, T. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.05.001 · Cited by 33
Assis, L. C., Rezin, G. T., Comim, C. M., Valvassori, S. S., Jeremias, I. C., Zugno, A. I., Quevedo, J., & STRECK, E. L. (2009) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462009000300010 · Cited by 34
Self-citationLiu, W., Yan, H., Zhou, D., Cai, X. M., Zhang, Y., Li, S., Li, H., Li, S., Zhou, D., Li, X., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0675-3 · Cited by 34
Głombik, K., Stachowicz, A., Olszanecki, R., Ślusarczyk, J., Trojan, E., Lasoń, W., Kubera, M., Budziszewska, B., Spedding, M., & Basta‐Kaim, A. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9807-4 · Cited by 32
“Most data indicated that chronic stress in rats decreased the activity of SDH in the brain [38].”
Metadata
- Authors
- Rezin, G. T., Cardoso, M. R., Gonçalves, C. L., Scaini, G., Fraga, D. B., Riegel, R. E., Comim, C. M., Quevedo, J., & Streck, E. L.
- Affiliations
- Universidade do Extremo Sul Catarinense (BR)
- Corresponding author
- Streck, Emilio L.
- ORCID
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 53
- Issue
- 6-8
- Pages
- 395-400
- ISSN
- 0197-0186 (ISSN-L)
- OpenAlex
- W1996982207
- Cited by
- 197
- References
- 63
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 9 · 2020: 19 · 2019: 21 · 2018: 20 · 2017: 11 · 2016: 14 · 2015: 7 · 2014: 12 · 2013: 9 · 2012: 7
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemistry International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, chronic stress, mitochondrial respiratory chain, mitochondrial complex I inhibition, complex III inhibition, complex IV inhibition, creatine kinase, brain energy metabolism, cerebral cortex, cerebellum, adrenal weight, sweets consumption, rat model of depression
- MeSH terms
- Adrenal Glands, Animals, Appetite Regulation, Body Weight, Brain, Brain Diseases, Metabolic, Chronic Disease, Creatine Kinase, Depressive Disorder, Disease Models, Animal, Electron Transport, Energy Metabolism, Male, Mitochondria, Organ Size, Oxidative Phosphorylation, Stress, Psychological, Biomarkers, Down-Regulation, Rats, Wistar, Rats
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