Mitochondrial Dysfunction and Oxidative Stress

Kato, Takeshi; Kapczinski, Flávio; Berk, Michael

doi:10.1002/9780470661277.ch18

Cited by 5 publications

(2 citation statements)

References 125 publications

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“…NAC reverses models of glutathione depletion, increasing peripheral [ 37 ] and brain glutathione [ 38 ]. There appears to be reduced neurogenesis in mood disorders, and antidepressants and mood stabilizers enhance neurogenesis [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

Berk

Dean

Cotton

et al. 2012

BMC Med

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BackgroundN-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.MethodThe efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.ResultsThere was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.ConclusionsThere were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations.Trial RegistrationThe trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

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Section: Discussionmentioning

confidence: 99%

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

Berk

Dean

Cotton

et al. 2012

BMC Med

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“…1A, center and right), a morphology that also occurs under conditions of apoptosis [28]. Since mitochondrial dysfunction has been related with an elevated production of reactive oxygen species (ROS) [29,30] and also with increased superoxide production [31,22], we next analyzed the mitochondrial membrane potential by flow cytometry using TMRhodamine (TMRM) and found that it was decreased in LD human fibroblasts (Fig. 1B, the mitochondrial uncoupler CCCP was used as a positive control).…”

Section: Human Fibroblasts From Ld Patients Show Impaired Mitochondrimentioning

confidence: 99%

Increased Oxidative Stress and Impaired Antioxidant Response in Lafora Disease

et al. 2014

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Lafora disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains largely unknown. Since autophagy impairment has been reported as a characteristic treat in both Lafora disease cell and animal models, and as there is a link between autophagy and mitochondrial performance, we sought to determine if mitochondrial function could be altered in those models. Using fibroblasts from LD patients, deficient in laforin or malin, we found mitochondrial alterations, oxidative stress and a deficiency in antioxidant enzymes involved in the detoxification of reactive oxygen species (ROS). Similar results were obtained in brain tissue samples from transgenic mice deficient in either the EPM2A or EPM2B genes. Furthermore, in a proteomic analysis of brain tissue obtained from Epm2b-/- mice, we observed an increase in a modified form of peroxiredoxin-6, an antioxidant enzyme involved in other neurological pathologies, thus corroborating an alteration of the redox condition. These data support that oxidative stress produced by an increase in ROS production and an impairment of the antioxidant enzyme response to this stress play an important role in development of LD.

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Neurochemical and Metabolic Imaging in Bipolar Disorder

Strakowski¹

2012

The Bipolar Brain

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Magnetic resonance spectroscopy (MRS) is an important neuroimaging technique offering the promise of revolutionizing how we study human brain function by allowing the examination of molecular processes in the live human brain. This chapter reviews both proton (1H) and phosphorus (31P) MRS studies in bipolar disorder and proposes a neurochemical model of this illness. Integration of the MRS findings including alterations in cerebral levels of N-acetyl aspartate, glutamate/glutamine, choline-containing compounds, myo-inositol, and lactate, measured using 1H MRS and alterations in cerebral levels of phosphocreatine, phosphomonoesters, and intracellular pH, measured using 31P MRS, leads to a well-supported hypothesis of an underlying mitochondrial impairment in bipolar disorder.

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Mitochondrial Dysfunction and Oxidative Stress

Cited by 5 publications

References 125 publications

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

Increased Oxidative Stress and Impaired Antioxidant Response in Lafora Disease

Neurochemical and Metabolic Imaging in Bipolar Disorder

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