Dataset Information

Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1.

ABSTRACT: Adenosine deaminase acting on RNA1 (ADAR1) is a newly discovered epigenetic molecule marker that is sensitive to environmental stressors. A recent study has demonstrated that ADAR1 affects BDNF expression via miR-432 and is involved in antidepressant action. However, the detailed molecular mechanism is still unclear. We have uncovered a new molecular mechanism showing the involvement of miR-432 and circ_0000418 in mediating the antidepressant action of ADAR1. We demonstrate that the ADAR1 inducer (IFN-γ) alleviates the depressive-like behaviors of BALB/c mice treated with chronic unpredictable stress (CUS) exposure. Moreover, both in vivo and in vitro studies show that ADAR1 differently impacts miR-432 and circ_0000418 expressions. Furthermore, the in vitro results demonstrate that circ_0000418 oppositely affects BDNF expression. Together, our results indicate that ADAR1 affects CUS-induced depressive-like behavior and BDNF expression by acting on miR-432 and circ_0000418. Elucidation of this new molecular mechanism will not only provide insights into further understanding the important role of ADAR1 in stress-induced depressive-like behavior but also suggest a potential therapeutic strategy for developing novel anti-depressive drugs.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8449188 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1.

Zhang Xiaonan X Yan Wei W Xue Ying Y Xu Hong H Li Jinying J Zhao Ziwei Z Sun Ye Y Wang Yanfang Y He Jiaqian J Huang Yuyue Y Yu Deqin D Xiao Zhaoyang Z Yin Shengming S

Neurobiology of stress 20210911

Adenosine deaminase acting on RNA1 (ADAR1) is a newly discovered epigenetic molecule marker that is sensitive to environmental stressors. A recent study has demonstrated that ADAR1 affects BDNF expression via miR-432 and is involved in antidepressant action. However, the detailed molecular mechanism is still unclear. We have uncovered a new molecular mechanism showing the involvement of miR-432 and circ_0000418 in mediating the antidepressant action of ADAR1. We demonstrate that the ADAR1 induce ...[more]

PMID: 34568523

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Project description:Introduction: Depression is a complex psychiatric disorder with substantial societal impact. While current antidepressants offer moderate efficacy, their adverse effects and limited understanding of depression's pathophysiology hinder the development of more effective treatments. Amidst this complexity, the role of neuroinflammation, a recognized but poorly understood associate of depression, has gained increasing attention. This study investigates hydroxytyrosol (HT), an olive-derived phenolic antioxidant, for its antidepressant and anti-neuroinflammatory properties based on mitochondrial protection. Methods: In vitro studies on neuronal injury models, the protective effect of HT on mitochondrial ultrastructure from inflammatory damage was investigated in combination with high-resolution imaging of mitochondrial substructures. In animal models, depressive-like behaviors of chronic restraint stress (CRS) mice and chronic unpredictable mild stress (CUMS) rats were examined to investigate the alleviating effects of HT. Targeted metabolomics and RNA-Seq in CUMS rats were used to analyze the potential antidepressant pathways of HT. Results: HT protected mitochondrial ultrastructure from inflammatory damage, thus exerting neuroprotective effects in neuronal injury models. Moreover, HT reduced depressive-like behaviors in mice and rats exposed to CRS and CUMS, respectively. HT's influence in the CRS model included alleviating hippocampal neuronal damage and modulating cytokine production, mitochondrial dysfunction, and brain-derived neurotrophic factor (BDNF) signaling. Targeted metabolomics in CUMS rats revealed HT's effect on neurotransmitter levels and tryptophan-kynurenine metabolism. RNA-Seq data underscored HT's antidepressant mechanism through the BDNF/TrkB signaling pathways, key in nerve fiber functions, myelin formation, microglial differentiation, and neural regeneration. Discussion: The findings underscore HT's potential as an anti-neuroinflammatory treatment for depression, shedding light on its antidepressant effects and its relevance in nutritional psychiatry. Further investigations are warranted to comprehensively delineate its mechanisms and optimize its clinical application in depression treatment.

Project description:Background: The diagnosis and monitoring of Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis typically rely on clinical manifestations and the detecting of anti-NMDAR antibodies. However, several studies have found that anti-NMDAR IgG in serum is not entirely specific and can be detected in about 3% of healthy individuals. Objective: To identify novel biomarkers that can accurately monitor the severity of anti-NMDAR encephalitis. Methods: We enrolled 9 patients with anti-NMDAR encephalitis and categorized them into an acute-phase group and a stable-phase group based on the duration of illness and disease severity. The clinical severity of the patients was assessed using the modified Rankin Scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). Then, we isolated exosomal miRNAs from plasma samples and analysed the differentially expressed miRNAs through next-generation sequencing. The sequencing results were validated using RT-qPCR. Furthermore, we conducted correlation analyses between miRNAs and clinical severity. Finally, we performed the functional pathways analysis to explore the underlying mechanisms in anti-NMDAR encephalitis. Results: We have found that exosomal miR-432-5p, miR-4433b-5p and miR-599 exhibited significant differences between patients with anti-NMDAR encephalitis and healthy controls, as well as at different stages of the disease. The expressions of miR-432-5p and miR-4433b-5p were negatively correlated with both the mRS and the CASE. We further identified that the pathways involved in rhythmic processes and neuroinflammation, as well as glutamatergic signaling, play significant roles in the pathogenesis of anti-NMDAR encephalitis. Conclusions: Our research indicates that exosomal miR-432-5p, miR-4433b-5p and miR-599 were highly correlated with the severity of anti-NMDAR encephalitis and can serve as potential biomarkers for disease monitoring. We further identified the pathways play significant roles in anti-NMDAR encephalitis. By modulating the functions of these crucial pathways, we can potentially uncover novel therapeutic targets and improve patient outcomes.

Dataset Information

Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1.

Publications

Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1.

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