Activity of mitochondrial respiratory chain is increased by chronic administration of antidepressants

Scaini, Giselli; Maggi, Débora D.; De-Nês, Bruna Tramontin; Gonçalves, Cinara L.; Ferreira, Gabriela K.; Teodorak, Brena P.; Bez, Gisele Daiane; Ferreira, Gustavo C.; Schuck, Patrícia Fernanda; Quevedo, Joao L De; Streck, Emílio L.

doi:10.1111/j.1601-5215.2011.00548.x

Cited by 41 publications

(29 citation statements)

References 53 publications

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“…Mitochondrial abnormalities including alterations in energy metabolism such as citrate cycle and glycolysis have previously been implicated in the pathobiology of affective disorders. 47 , 48 , 49 , 55 , 56 , 57 , 58 , 59 , 60 We observed several metabolite level and metabolite ratio changes of the citrate cycle already 2 h after Ketamine treatment (fumarate, malate, citrate and isocitrate, alpha-ketoglutarate/isocitrate levels increase; succinate, acetyl-CoA and succinate-CoA, citrate/acetyl-CoA and succinate/fumarate levels decrease; Figure 2a ). Alterations in metabolite ratios can reflect changes in enzyme activities or protein expression.…”

Section: Discussionmentioning

confidence: 88%

Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal pathway alterations and biomarker candidates

et al. 2014

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Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has fast-acting antidepressant activities and is used for major depressive disorder (MDD) patients who show treatment resistance towards drugs of the selective serotonin reuptake inhibitor (SSRI) type. In order to better understand Ketamine's mode of action, a prerequisite for improved drug development efforts, a detailed understanding of the molecular events elicited by the drug is mandatory. In the present study we have carried out a time-dependent hippocampal metabolite profiling analysis of mice treated with Ketamine. After a single injection of Ketamine, our metabolomics data indicate time-dependent metabolite level alterations starting already after 2 h reflecting the fast antidepressant effect of the drug. In silico pathway analyses revealed that several hippocampal pathways including glycolysis/gluconeogenesis, pentose phosphate pathway and citrate cycle are affected, apparent by changes not only in metabolite levels but also connected metabolite level ratios. The results show that a single injection of Ketamine has an impact on the major energy metabolism pathways. Furthermore, seven of the identified metabolites qualify as biomarkers for the Ketamine drug response.

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Section: Discussionmentioning

confidence: 88%

Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal pathway alterations and biomarker candidates

et al. 2014

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“…Changes in mitochondrial size, distribution and function are observed in MDD. 153 Antidepressants and lithium upregulate mitochondrial energy generation, 154 and N-acetylcysteine (NAC) enhanced mitochondrial function and cognition in an animal model of mitochondrial dysfunction. 4 Mitochondrial dysfunction impairs neural progenitor cell function 155 and can result from action of various inflammatory mediators including TNF-a, IL-6 and ROS.…”

Section: Oandns and Mitochondrial Dysfunctionsmentioning

confidence: 99%

The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications

Maes²,

et al. 2012

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In some patients with major depressive disorder (MDD), individual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems, inflammatory, oxidative and nitrosative stress pathways, neurotrophins and regulation of neurogenesis, cortisol and the hypothalamic-pituitary-adrenal axis modulation, mitochondrial dysfunction and epigenetic and dietary influences. Evidence-based novel treatments informed by this knowledge are discussed.

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“…Peroxiredoxin 5 was also altered in both disorders, which may be evidence of an increase in ROS due to poor mitochondrial functioning (Manji et al, 2012 ). Antidepressants used in the treatment of MDD, along with lithium which is generally used in BPD treatment, have an effect on the upregulation of mitochondrial energy generation (Scaini et al, 2011 ).…”

Section: What Can Proteomics Tell Us About Energy Metabolism Dysfunctmentioning

confidence: 99%

The Energy Metabolism Dysfunction in Psychiatric Disorders Postmortem Brains: Focus on Proteomic Evidence

et al. 2017

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Psychiatric disorders represent a great medical and social challenge and people suffering from these conditions face many impairments regarding personal and professional life. In addition, a mental disorder will manifest itself in approximately one quarter of the world's population at some period of their life. Dysfunction in energy metabolism is one of the most consistent scientific findings associated with these disorders. With this is mind, this review compiled data on disturbances in energy metabolism found by proteomic analyses of postmortem brains collected from patients affected by the most prevalent psychiatric disorders: schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD). We searched in the PubMed database to gather the studies and compiled all the differentially expressed proteins reported in each work. SCZ studies revealed 92 differentially expressed proteins related to energy metabolism, while 95 proteins were discovered in BPD, and 41 proteins in MDD. With the compiled data, it was possible to determine which proteins related to energy metabolism were found to be altered in all the disorders as well as which ones were altered exclusively in one of them. In conclusion, the information gathered in this work could contribute to a better understanding of the impaired metabolic mechanisms and hopefully bring insights into the underlying neuropathology of psychiatric disorders.

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Activity of mitochondrial respiratory chain is increased by chronic administration of antidepressants

Cited by 41 publications

References 53 publications

Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal pathway alterations and biomarker candidates

Time-dependent metabolomic profiling of Ketamine drug action reveals hippocampal pathway alterations and biomarker candidates

The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications

The Energy Metabolism Dysfunction in Psychiatric Disorders Postmortem Brains: Focus on Proteomic Evidence

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