MicroRNA-132 may play a role in coexistence of depression and cardiovascular disease: A hypothesis

Xu, Feng

doi:10.12659/msm.883935

Cited by 20 publications

(7 citation statements)

References 70 publications

(64 reference statements)

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“…We also validated the reduced expression of miR-132, by RT-qPCR in these samples (Figure 3B). Since miR-132 has been widely reported to regulate neuroplasticity and neural activity (Luikart et al, 2011; Zheng et al, 2013), compromised hippocampal synaptic plasticity observed in stress and depression (Pittenger and Duman, 2008), and also in our study of socially defeated mice could be attributed to the attenuated expression of miR-132. There is no human study till date that shows our novel findings (dysregulation of Drosha and a number of miRNAs, including mir-30 family members in mouse DG in CSDS model of depression) in post mortem brain samples from depressed individuals.…”

Section: Discussionsupporting

confidence: 55%

miR-30 Family miRNAs Mediate the Effect of Chronic Social Defeat Stress on Hippocampal Neurogenesis in Mouse Depression Model

Khandelwal

Dey

Chakravarty

et al. 2019

Front. Mol. Neurosci.

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Depression is a debilitating psychiatric disorder with a high rate of relapse and a low rate of response to antidepressant treatment. There is a dearth of new antidepressants due to an incomplete understanding of the molecular mechanisms involved in its etiopathology. Chronic stress appears to be one of the foremost underlying causes of depression. Studies in animal models in the past decade have implicated epigenetic mechanisms in mediating the negative effects of chronic stressful events on the progression/manifestation of depression and other co-morbid neuropsychiatric disorders. However, non-coding RNAs, another layer of epigenetic regulation is relatively less studied in depression. Here, using the chronic social defeat stress (CSDS)-induced depression model, we hypothesized dysregulation in miRNA-mRNA networks in the neurogenic dentate gyrus (DG) region of male C57BL/6 mice. Among several dysregulated miRNAs identified via miRNA arrays, the most striking finding was the downregulation of miRNAs of the miR-30 family in stressed/defeated mice. To investigate miRNAs in the DG-resident neural stem/progenitor cells (NSCs/NPCs), we used the in vitro neurosphere culture, where proliferating NSCs/NPCs were subjected to differentiation. Among several differentially expressed miRNAs, we observed an upregulation of miR-30 family miRNAs upon differentiation. To search for the gene targets of these miRNAs, we performed gene arrays followed by bioinformatics analysis, miRNA manipulations and luciferase assays. Our results suggest that miR-30 family miRNAs mediate chronic stress-induced depression-like phenotype by altering hippocampal neurogenesis and neuroplasticity via controlling the epigenetic and transcription regulators such as Mll3 and Runx1 ; and cell signaling regulators like Socs3, Ppp3r1, Gpr125 , and Nrp1 .

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Section: Discussionsupporting

confidence: 55%

miR-30 Family miRNAs Mediate the Effect of Chronic Social Defeat Stress on Hippocampal Neurogenesis in Mouse Depression Model

Khandelwal

Dey

Chakravarty

et al. 2019

Front. Mol. Neurosci.

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“…34 Masson et al 35 observed that higher circulating levels of miR-132 were independently related to higher diastolic blood pressure, ischemic etiology of heart failure, higher cholesterol, and more severe symptoms of heart failure. Although the expression of miR-132 has been identified in cardiovascular disease, 36 the underlying functions and mechanisms in DCM have not been fully studied. Our findings provided evidence that miR-132 could suppress cardiocyte apoptosis and cardiac fibrosis while boosting proliferation.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Upregulated microRNA‐132 rescues cardiac fibrosis and restores cardiocyte proliferation in dilated cardiomyopathy through the phosphatase and tensin homolog–mediated PI3K/Akt signal transduction pathway

Zhang

Huang

et al. 2018

J of Cellular Biochemistry

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Cardiac fibrosis is known to be present in dilated cardiomyopathy (DCM) and it predicts the occurrence of sudden death and congestive heart failure. The aim of our study is to investigate the expression of microRNA-132 (miR-132) and its effect on cardiocyte proliferation, apoptosis, and cardiac fibrosis by binding to phosphatase and tensin homolog (PTEN) through the phosphateidylinositol 3-kinase (PI3K)/protein kinase (Akt) signal transduction pathway in DCM rats. DCM rat models induced by doxorubicin were established and confirmed by an ultrasonic cardiogram. Epithelial cells were treated with inhibitors, activators, and small interfering RNAs to identify the mechanisms by which miR-132 controls cardiocyte activity and cardiac fibrosis. Angiotensin II (Ang II) and aldosterone (ALD) expressions were detected by an enzyme-linked immunosorbent assay. The relationship between PTEN and miR-132 was verified by a dual-luciferase reporter assay. Cell proliferation and apoptosis were tested by the MTT assay and flow cytometry. PTEN was determined to be the target gene of miR-132. Rat models of DCM exhibited a lower level of miR-132, PI3K, Akt, B-cell lymphoma 2, collagen I, and collagen III, but a higher level of PTEN, Bcl-2-associated X protein, and proliferating cell nuclear antigen as well as inflammatory response (Ang II and ALD), accompanied by declined cardiocyte proliferation and elevated apoptosis and cardiac fibrosis. Upregulated miR-132 or silenced PTEN activated the PI3K/Akt pathway, thus facilitating cardiocyte proliferation and repressing cardiocyte apoptosis and cardiac fibrosis, as well as inflammatory responses. Downregulated miR-132 reversed this tendency. These findings indicate that miR-132 activates the PI3K/Akt pathway by inhibiting PTEN expression, thus facilitating cardiocyte proliferation and inhibiting apoptosis and cardiac fibrosis in DCM rats.

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“…Some estimates show that by 2020 the disease will be the second-most serious illness in terms of social and economic burden, exceeded only by ischemic heart disease [ 2 , 3 ]. Moreover, there are some reports suggesting that depression may coexist with other diseases, like cardiovascular disease [ 4 ]. To make matters worse, approximately one-third of DD patients do not respond to traditional pharmacological medications such as monoamine reuptake inhibitors [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Elevated Level of DNA Damage and Impaired Repair of Oxidative DNA Damage in Patients with Recurrent Depressive Disorder

et al. 2015

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BackgroundDepressive disorder (DD), including recurrent DD (rDD), is a severe psychological disease, which affects a large percentage of the world population. Although pathogenesis of the disease is not known, a growing body of evidence shows that inflammation together with oxidative stress may contribute to development of DD. Since reactive oxygen species produced during stress may damage DNA, we wanted to evaluate the extent of DNA damage and efficiency of DNA repair in patients with depression.Material/MethodsWe measured and compared the extent of endogenous DNA damage – single- and double-strand breaks, alkali-labile sites, and oxidative damage of the pyrimidines and purines – in peripheral blood mononuclear cells isolated from rDD patients (n=40) and healthy controls (n=46) using comet assay. We also measured DNA damage evoked by hydrogen peroxide and monitored changes in DNA damage during repair incubation.ResultsWe found an increased number DNA breaks, alkali-labile sites, and oxidative modification of DNA bases in the patients compared to the controls. Exposure to hydrogen peroxide evoked the same increased damage in both groups. Examination of the repair kinetics of both groups revealed that the lesions were more efficiently repaired in the controls than in the patients.ConclusionsFor the first time we showed that patients with depression, compared with non-depresses individuals, had more DNA breaks, alkali-labile sites, and oxidative DNA damage, and that those lesions may be accumulated by impairments of the DNA repair systems. More studies must be conducted to elucidate the role of DNA damage and repair in depression.

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MicroRNA-132 may play a role in coexistence of depression and cardiovascular disease: A hypothesis

Cited by 20 publications

References 70 publications

miR-30 Family miRNAs Mediate the Effect of Chronic Social Defeat Stress on Hippocampal Neurogenesis in Mouse Depression Model

miR-30 Family miRNAs Mediate the Effect of Chronic Social Defeat Stress on Hippocampal Neurogenesis in Mouse Depression Model

Retracted: Upregulated microRNA‐132 rescues cardiac fibrosis and restores cardiocyte proliferation in dilated cardiomyopathy through the phosphatase and tensin homolog–mediated PI3K/Akt signal transduction pathway

Elevated Level of DNA Damage and Impaired Repair of Oxidative DNA Damage in Patients with Recurrent Depressive Disorder

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