Depression and neuroprogression: Sirtuins and mitochondria as crucial hubs

2019 ◽  
pp. 77-106
Author(s):  
George Anderson ◽  
Michael Maes
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mitochondrial Dysfunction ◽  
Nitrosative Stress ◽  
Whole Body ◽  
Oxidative And Nitrosative Stress ◽  
Psychiatric Classification ◽  
Biochemical Alterations ◽  
Tryptophan Catabolites ◽  
Early Developmental

Neuroprogressive processes in major depressive disorder (MDD) can occur in association with recurrent episodes. The primary biological underpinnings are mediated by increases in the levels of immune-inflammation, tryptophan catabolites, mitochondrial dysfunction, and oxidative and nitrosative stress. Such biochemical alterations may be driven by changes in many peripheral and central sites, including in the gut, as well as by early developmental priming, such as prenatal stressors and breastfeeding consequences. As such, the conceptualization of MDD is shifted from simple psychological and central biochemical models to one that includes whole body processes over a developmental timescale. This provides a model that better integrates wider bodies of data relevant to the aetiology and course of MDD, and which therefore underpins the neuroprogressive processes that can occur over the course of MDD. This also significantly challenges current MDD (and wider psychiatric) classification by shifting classification to one based on biological processes rather than one based on subjective phenomenology.

Cognitive Enhancement in Major Depressive Disorder

2017 ◽  
Author(s):  
André F. Carvalho ◽  
Gilberto S. Alves ◽  
Cristiano A. Köhler ◽  
Roger S. McIntyre
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Nitrosative Stress ◽  
Antidepressant Drugs ◽  
Cognitive Remediation ◽  
Therapeutic Benefit ◽  
Psychosocial Burden ◽  
Major Depressive ◽  
Oxidative And Nitrosative Stress ◽  
Neurotrophin Signaling

Major depressive disorder (MDD) is a chronic and disabling illness often associated with elevated rates of non-recovery and substantial psychosocial burden. Cognitive impairment is a common residual manifestations of MDD. Overactivation of the hypothalamic–pituitary–adrenal axis, along with immune–inflammatory imbalances, a decrease in neurotrophin signaling, and an increase in oxidative and nitrosative stress, leads to neuroprogression and cognitive deterioration in MDD. “Cognitive remission” has been proposed as a novel treatment target for MDD. Cognitive remediation therapy has provided encouraging results for the management of cognitive deficits in MDD. The effects of standard antidepressant drugs on MDD-related cognitive dysfunction are often suboptimal, which calls for the development of novel agents with the potential to target cognitive impairments in MDD. The incorporation of biobehavioral strategies (e.g., exercise) and multimodal treatment approaches (e.g., cognitive training, antidepressant therapy, and neuromodulation) is more likely to generate therapeutic benefit.

DNA damage and repair in neuropsychiatric disorders. What do we know and what are the future perspectives?

Mutagenesis ◽  
2019 ◽  
Author(s):  
Piotr Czarny ◽  
Katarzyna Bialek ◽  
Sylwia Ziolkowska ◽  
Justyna Strycharz ◽  
Tomasz Sliwinski
Keyword(s):  
Dna Damage ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Nitrosative Stress ◽  
Nuclear Dna ◽  
Neuropsychiatric Disorders ◽  
Dna Lesions ◽  
Major Depressive ◽  
Oxidative And Nitrosative Stress ◽  
Dna Damage And Repair

Abstract Over the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress is known to induce oxidative damage to biomolecules, including DNA. Accordingly, increased mitochondrial and nuclear DNA, as well as RNA damage, were observed in patients suffering from these diseases. However, recent findings indicate that the patients are characterised by impaired DNA repair pathways, which may suggest that these DNA lesions could be also a result of their insufficient repair. In the current systematic, critical review, we aim to sum up, using available literature, the knowledge about the involvement of nuclear and mitochondrial DNA damage and repair, as well as about damage to RNA in pathoetiology of neuropsychiatric disorders, i.e., AD, PD, ALS, BD, schizophrenia and major depressive disorder, as well as the usefulness of the discussed factors as being diagnostic markers and targets for new therapies. Moreover, we also underline the new directions to which future studies should head to elucidate these phenomena.

scholarly journals Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
João Paulo Silva Nunes ◽  
Pauline Andrieux ◽  
Pauline Brochet ◽  
Rafael Ribeiro Almeida ◽  
Eduardo Kitano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Chagas Disease ◽  
Nitrosative Stress ◽  
Acid Oxidation ◽  
Oxidative And Nitrosative Stress ◽  
Human Cardiomyocytes ◽  
Tnf Α ◽  
Ifn Γ

Infection by the protozoan Trypanosoma cruzi causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume and produce 95% of cellular ATP that sustain the life-long cycles of heart contraction. As IFN-γ and TNF-α have been described to affect mitochondrial function, we hypothesized that IFN-γ and TNF-α are involved in the myocardial mitochondrial dysfunction observed in CCC patients. In this study, we quantified markers of mitochondrial dysfunction and nitro-oxidative stress in CCC heart tissue and in IFN-γ/TNF-α-stimulated AC-16 human cardiomyocytes. We found that CCC myocardium displayed increased levels of nitro-oxidative stress and reduced mitochondrial DNA as compared with myocardial tissue from patients with dilated cardiomyopathy (DCM). IFN-γ/TNF-α treatment of AC-16 cardiomyocytes induced increased nitro-oxidative stress and decreased the mitochondrial membrane potential (ΔΨm). We found that the STAT1/NF-κB/NOS2 axis is involved in the IFN-γ/TNF-α-induced decrease of ΔΨm in AC-16 cardiomyocytes. Furthermore, treatment with mitochondria-sparing agonists of AMPK, NRF2 and SIRT1 rescues ΔΨm in IFN-γ/TNF-α-stimulated cells. Proteomic and gene expression analyses revealed that IFN-γ/TNF-α-treated cells corroborate mitochondrial dysfunction, transmembrane potential of mitochondria, altered fatty acid metabolism and cardiac necrosis/cell death. Functional assays conducted on Seahorse respirometer showed that cytokine-stimulated cells display decreased glycolytic and mitochondrial ATP production, dependency of fatty acid oxidation as well as increased proton leak and non-mitochondrial oxygen consumption. Together, our results suggest that IFN-γ and TNF-α cause direct damage to cardiomyocytes’ mitochondria by promoting oxidative and nitrosative stress and impairing energy production pathways. We hypothesize that treatment with agonists of AMPK, NRF2 and SIRT1 might be an approach to ameliorate the progression of Chagas disease cardiomyopathy.

Alterations of rCBF and mitochondrial dysfunction in major depressive disorder: a case report

2003 ◽  
Vol 107 (3) ◽  
pp. 233-239 ◽  
Author(s):  
A. Gardner ◽  
M. Pagani ◽  
R. Wibom ◽  
I. Nennesmo ◽  
H. Jacobsson ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Case Report ◽  
Depressive Disorder ◽  
Mitochondrial Dysfunction ◽  
Major Depressive

Abstract # 1746 Inflammation and mitochondrial dysfunction in elderly women with major depressive disorder

2016 ◽  
Vol 57 ◽  
pp. e11-e12
Author(s):  
C. Boeck ◽  
A. Karabatsiakis ◽  
J. Salinas-Manrique ◽  
E. Calzia ◽  
S. Kolassa ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mitochondrial Dysfunction ◽  
Elderly Women ◽  
Major Depressive
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