MicroRNAs as Critical Biomarkers of Major Depressive Disorder: A Comprehensive Perspective

Ortega, Miguel Á.; Álvarez-Mon, Miguel Ángel; García-Montero, Cielo; Fraile-Martínez, Óscar; Lahera, Guillermo; Monserrat, Jorge; Muñoz-Merida, Luis; Mora, Fernando A. Lázaro; Rodríguez‐Jiménez, Roberto; Fernandez-Rojo, Sonia; Quintero, Javier; Álvarez‐Mon, Melchor

doi:10.3390/biomedicines9111659

Cited by 30 publications

(22 citation statements)

References 279 publications

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“…The modifications that cause those events can be mediated by DNA methylation, histone modification, and also the expression of signaling non-coding RNAs, mainly represented by long-noncoding RNAs (lncRNAs) and microRNAs (miRNAs) ( 23 – 25 ). That epigenetic regulation can occur not only from nervous system development but also in the mature brain with long-lasting effects and the possibility to be heritable for multiple generations ( 26 ).…”

Section: Epigenetic Basis Of Mddmentioning

confidence: 99%

“…These changes can lead to maladaptive neuronal plasticity, poorer resilience to stress, depressive mood, and different response to antidepressants ( 27 ). Recent work reviews have denoted the lack of information regarding the validation of depression-associated epigenetic modifications due to the short age of this field of study, the small sample size of patients, and the difficulties to study functioning changes in alive brains instead of postmortem ( 23 ), although there are some epigenetic markers that could be studied in serum and body fluids such as miRNAs ( 25 ). Besides, sometimes it is not possible to establish a clear causality of the epigenetic findings because of the difficulty of replicate the experimental results from animals to humans ( 28 ).…”

Section: Epigenetic Basis Of Mddmentioning

confidence: 99%

“…During the last decade, numerous miRNAs with pleiotropic effects have been identified to be involved in several processes that concern MDD pathogenesis, including neuroinflammation, endotoxemia, microglial apoptosis, altered neurotransmission, worse stress response and sensitivity, altered cell signaling, and circadian disruption. Most of these effects are reviewed and summarized by Ortega et al ( 25 ). In light of the evidence, it is undeniable that miRNAs are key elements implicated in MDD pathogenesis, representing promising therapeutical targets ( 63 ).…”

Section: Epigenetic Basis Of Mddmentioning

confidence: 99%

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Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection

et al. 2022

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Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.

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Section: Epigenetic Basis Of Mddmentioning

confidence: 99%

Section: Epigenetic Basis Of Mddmentioning

confidence: 99%

Section: Epigenetic Basis Of Mddmentioning

confidence: 99%

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Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection

et al. 2022

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“…They showed that the miR-29b-3p expression levels in the CSF were significantly higher in depressed patients than they were in the control subjects, suggesting the involvement of increased miR-29b expression in depression-related AAA development. Compared to miRNA-29b, the miRNA-146a expression level in patients with MMD has been studied more extensively [ 43 , 44 ]. Hung et al showed that the miRNA-146a levels in the peripheral blood monocytes from MDD patients were significantly lower than they were in healthy controls, which was partially restored after antidepressant treatment [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Repeated Social Defeat Enhances CaCl2-Induced Abdominal Aortic Aneurysm Expansion by Inhibiting the Early Fibrotic Response via the MAPK-MKP-1 Pathway

Kubota

Yamada

Sugimoto

et al. 2022

Cells

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Depression is an independent risk factor for cardiovascular disease and is significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We investigated the effect of repeated social defeat (RSD) on AAA development. Eight-week-old male wild-type mice were exposed to RSD by being housed with larger CD-1 mice in a shared cage. They were subjected to vigorous physical contact. After the confirmation of depressive-like behavior, calcium chloride was applied to the infrarenal aorta of the mice. At one week, AAA development was comparable between the defeated and control mice, without any differences being observed in the accumulated macrophages or in the matrix metalloproteinase activity. At two weeks, the maximum diameter and circumference of the aneurysm were significantly increased in the defeated mice, and a significant decrease in periaortic fibrosis was also observed. Consistently, the phosphorylation of the extracellular signal-regulated kinase and the incorporation of 5-bromo-2′-deoxyuridine in the primarily cultured aortic vascular smooth muscle cells were significantly reduced in the defeated mice, which was accompanied by a substantial increase in mitogen-activated protein kinase phosphatase-1 (MKP-1). The MKP-1 mRNA and protein expression levels during AAA were much higher in the defeated mice than they were in the control mice. Our findings demonstrate that RSD enhances AAA development by suppressing periaortic fibrosis after an acute inflammatory response and imply novel mechanisms that are associated with depression-related AAA development.

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“…Two central mechanisms should be highlighted to understand the anti-depressant effect of SCFAs: (1) epigenetic regulation and (2) immunomodulatory action. Depressed patients show a prominent epigenetic footprint in comparison to non-depressed subjects, including critical alterations in DNA methylation, histone modifications, and non-coding RNAs (i.e., microRNAs) [90][91][92]. SCFAs act as histone deacetylases (HDAC) inhibitors, playing a key role in the DNA methylation, histone modification, and chromatin restructuring to alter gene expression [93].…”

Section: Short-chain Fatty Acidsmentioning

confidence: 99%

Gut Microbiota Metabolites in Major Depressive Disorder—Deep Insights into Their Pathophysiological Role and Potential Translational Applications

et al. 2022

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The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of the organism, affecting the health and disease status of the individuals. There is continuous and bidirectional communication between gut microbiota and the host, conforming to a unique entity known as “holobiont”. Among these crosstalk mechanisms, the gut microbiota synthesizes a broad spectrum of bioactive compounds or metabolites which exert pleiotropic effects on the human organism. Many of these microbial metabolites can cross the blood–brain barrier (BBB) or have significant effects on the brain, playing a key role in the so-called microbiota-gut-brain axis. An altered Microbiota-Gut-Brain (MGB) axis is a major characteristic of many neuropsychiatric disorders, including major depressive disorder (MDD). Significative differences between gut eubiosis and dysbiosis in mental disorders like MDD with their different metabolite composition and concentrations are being discussed. In the present review, the main microbial metabolites (short-chain fatty acids -SCFAs-, bile acids, amino acids, tryptophan -trp- derivatives, and more), their signaling pathways and functions will be summarized to explain part of MDD pathophysiology. Conclusions from promising translational approaches related to microbial metabolome will be addressed in more depth to discuss their possible clinical value in the management of MDD patients.

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MicroRNAs as Critical Biomarkers of Major Depressive Disorder: A Comprehensive Perspective

Cited by 30 publications

References 279 publications

Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection

Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection

Repeated Social Defeat Enhances CaCl2-Induced Abdominal Aortic Aneurysm Expansion by Inhibiting the Early Fibrotic Response via the MAPK-MKP-1 Pathway

Gut Microbiota Metabolites in Major Depressive Disorder—Deep Insights into Their Pathophysiological Role and Potential Translational Applications

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