Immune mechanisms linked to depression via oxidative stress and neuroprogression

Abstract

SummaryEmerging evidence suggests a significant role for inflammation and oxidative stress as main contributors to the neuroprogression that is observed in major depressive disorder (MDD), where patients show increased inflammatory and oxidative stress biomarkers. The process of neuroprogression includes stage-related neurodegeneration, cell death, reduced neurogenesis, reduced neuronal plasticity and increased autoimmune responses. Oxidative stress is a consequence of the biological imbalance between reactive oxygen species (ROS) and antioxidants, leading to the alteration of biomolecules and the loss of control of the intracellular redox-related signalling pathways. ROS serve as crucial secondary messengers in signal transduction and significantly affect inflammatory pathways by activating nuclear factor-jB and mitogen-activated protein kinase family stress kinases. When present in excess, ROS inflict damage, affecting cellular constituents with the formation of pro-inflammatory molecules, such as malondialdehyde, 4-hydroxynonenal, neoepitopes and damageassociated molecular patterns promoting immune response, and ultimately leading to cell death. The failure of cells to adapt to the changes in redox homeostasis and the subsequent cell death, together with the damage caused by inflammatory mediators, have been considered as major causes of neuroprogression and hence MDD. Both an activated immune-inflammatory system and increased oxidative stress act synergistically, complicating our understanding of the pathogenesis of depression. The cascade of antioxidative and inflammatory events is orchestrated by several transcription factors, with nuclear factor (erythroid-derived 2)-like 2 and nuclear factor-jB having particular relevance to MDD. This review focuses on potential molecular mechanisms through which impaired redox homeostasis and neuroinflammation can affect the neuronal environment and contribute to depression.

In vitroeffect of 4-pentylphenol and 3-methyl-4-nitrophenol on murine splenic lymphocyte populations and cytokine/granzyme production

“…However, it is well known that ROS plays a crucial role in immune damage progression (Bakunina et al 2015). Metabolic activation of GEP and DEP may lead to generation of ROS that are, in turn, responsible for their immunotoxicity (Yin et al 2004;Ohyama et al 2007).…”

Advances in Stem Cells Biology: New Approaches to Understand Depression

“…High levels of reactive oxygen species, shown in depressed patients, are known to affect cellular constituents, leading to neoepitopes and damage-associated molecular patterns that promote further immune responses (Bakunina et al 2015). Cells treated with TBHP showed a dose-dependent increase in lipid peroxidation as well as reduced cell viability.…”

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“…Основываясь на данных ранее про-веденных исследований, главный редактор Current Psychiatry Henry A. Nasrallah сделал заключение, что глав-ное -избежать триггеров, пусковых механизмов вос-паления. Он выделяет 10 факторов риска (ФР) разви-тия воспалительных явлений в тканях мозга: аллергия, нарушение проницаемости кишечника, ожирение, за-болевания полости рта (кариес, гингивит, пародон-тит), нерациональное питание, недостаток сна, мало-подвижный образ жизни, курение, стресс и дефицит ви-тамина Д. С его точки зрения, нивелирование ФР может предотвратить развитие депрессии или уменьшить тя-жесть симптомов и добиться стойкой ремиссии [2][3][4][5].…”

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