miR-145-5p/Nurr1/TNF-α Signaling-Induced Microglia Activation Regulates Neuron Injury of Acute Cerebral Ischemic/Reperfusion in Rats

Xie, Xuemei; Li, Peng; Zhu, Jing; Zhou, Yang; Li, Lingyu; Chen, Yanlin; Yu, Shanshan; Zhao, Yong

doi:10.3389/fnmol.2017.00383

Cited by 62 publications

(42 citation statements)

References 36 publications

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“…In this study, miR-155 and miR-145 were identified as the most significantly up-regulated miRNAs in the context of lipopolysaccharide-stimulation of microglia and interleukin-4 -stimulation of microglia, respectively. The differentiation regulation of miR-155 and miR-145 expression in microglial M1 versus M2 phenotypes, has been confirmed in the context of other stimuli promoting those phenotypes ( Cardoso et al, 2012 ; Woodbury et al, 2015 ; Qi et al, 2017 ; Xie et al, 2017 ; Yin H. et al, 2017 ). The microRNA miR-155 has gained particular attention in the context of ALS.…”

Section: Microrna and Long Non-coding Rnamentioning

confidence: 77%

Epigenetics Control Microglia Plasticity

Cheray

Joseph

2018

Front. Cell. Neurosci.

116

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Microglia, resident immune cells of the central nervous system, fulfill multiple functions in the brain throughout life. These microglial functions range from participation in innate and adaptive immune responses, involvement in the development of the brain and its homeostasis maintenance, to contribution to degenerative, traumatic, and proliferative diseases; and take place in the developing, the aging, the healthy, or the diseased brain. Thus, an impressive level of cellular plasticity, appears as a requirement for the pleiotropic biological functions of microglia. Epigenetic changes, including histone modifications or DNA methylation as well as microRNA expression, are important modifiers of gene expression, and have been involved in cell phenotype regulation and reprogramming and are therefore part of the mechanisms regulating cellular plasticity. Here, we review and discuss the epigenetic mechanisms, which are emerging as contributors to this microglial cellular plasticity and thereby can constitute interesting targets to modulate microglia associated brain diseases, including developmental diseases, neurodegenerative diseases as well as cancer.

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Section: Microrna and Long Non-coding Rnamentioning

confidence: 77%

Epigenetics Control Microglia Plasticity

Cheray

Joseph

2018

Front. Cell. Neurosci.

116

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“…Pitx3, a transcription factor involved in dopaminergic neuron generation and maintenance, and the dopamine transporter, DAT, are putative targets of miR‐133b. Nurr1, another transcription factor involved in dopaminergic neuron elaboration and survival, is a putative target of miR‐145 (TargetScan) (de Mena et al, ; Kim et al, ; Xie et al, ). Both MiR‐133b and miR‐145 were significantly upregulated in the TG striatum compared to WT striatum ( p = .004 and p = .05, respectively) and trended toward enhanced expression in the TG SN (Figure d).…”

Section: Resultsmentioning

confidence: 99%

GlialHMOX1expression promotes central and peripheral α‐synuclein dysregulation and pathogenicity in parkinsonian mice

Cressatti

Song

Turk

et al. 2019

Glia

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α‐Synuclein is a key player in the pathogenesis of Parkinson disease (PD). Expression of human heme oxygenase‐1 (HO‐1) in astrocytes of GFAP.HMOX1 transgenic (TG) mice between 8.5 and 19 months of age results in a parkinsonian phenotype characterized by neural oxidative stress, nigrostriatal hypodopaminergia associated with locomotor incoordination, and overproduction of α‐synuclein. We identified two microRNAs (miR‐), miR‐153 and miR‐223, that negatively regulate α‐synuclein in the basal ganglia of male and female GFAP.HMOX1 mice. Serum concentrations of both miRNAs progressively declined in the wild‐type (WT) and GFAP.HMOX1 mice between 11 and 19 months of age. Moreover, at each time point surveyed, circulating levels of miR‐153 were significantly lower in the TG animals compared to WT controls, while α‐synuclein protein concentrations were elevated in erythrocytes of the GFAP.HMOX1 mice at 19 months of age relative to WT values. Primary WT neurons co‐cultured with GFAP.HMOX1 astrocytes exhibited enhanced protein oxidation, mitophagy and apoptosis, aberrant expression of genes regulating the dopaminergic phenotype, and an imbalance in gene expression profiles governing mitochondrial fission and fusion. Many, but not all, of these neuronal abnormalities were abrogated by small interfering RNA (siRNA) knockdown of α‐synuclein, implicating α‐synuclein as a potent, albeit partial, mediator of HO‐1's neurodystrophic effects in these parkinsonian mice. Overexpression of HO‐1 in stressed astroglia has previously been documented in the substantia nigra of idiopathic PD and may promote α‐synuclein production and toxicity by downmodulating miR‐153 and/or miR‐223 both within the CNS and in peripheral tissues.

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“…Accumulating evidence indicates that miRNAs are involved in microglial function. miR-124 is involved in microglial polarization [41], and other miRNAs, including miR-let-7c-5p, miR-145-5p, miR-155, and miR-125b, are involved in microglial activation in different neuronal disorders [42][43][44][45]. In the context of depression, our previous work indicated that miR-9 regulates microglial activation induced by LPS, which is consistent with a recent study showing that circulating miR-9 is upregulated in the prefrontal cortex of a CUS model [24].…”

Section: Discussionmentioning

confidence: 99%

CircDYM ameliorates depressive-like behavior by targeting miR-9 to regulate microglial activation via HSP90 ubiquitination

et al. 2018

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Circular RNAs (circRNAs), highly expressed in the central nervous system, are involved in various regulatory processes and implicated in some pathophysiology. However, the potential role of circRNAs in psychiatric diseases, particularly major depressive disorder (MDD), remains largely unknown. Here, we demonstrated that circular RNA DYM (circDYM) levels were significantly decreased both in the peripheral blood of patients with MDD and in the two depressive-like mouse models: the chronic unpredictable stress (CUS) and lipopolysaccharide (LPS) models. Restoration of circDYM expression significantly attenuated depressive-like behavior and inhibited microglial activation induced by CUS or LPS treatment. Further examination indicated that circDYM functions as an endogenous microRNA-9 (miR-9) sponge to inhibit miR-9 activity, which results in a downstream increase of target-HECT domain E3 ubiquitin protein ligase 1 (HECTD1) expression, an increase of HSP90 ubiquitination, and a consequent decrease of microglial activation. Taken together, the results of our study demonstrate the involvement of circDYM and its coupling mechanism in depression, providing translational evidence that circDYM may be a novel therapeutic target for depression.

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miR-145-5p/Nurr1/TNF-α Signaling-Induced Microglia Activation Regulates Neuron Injury of Acute Cerebral Ischemic/Reperfusion in Rats

Cited by 62 publications

References 36 publications

Epigenetics Control Microglia Plasticity

Epigenetics Control Microglia Plasticity

GlialHMOX1expression promotes central and peripheral α‐synuclein dysregulation and pathogenicity in parkinsonian mice

CircDYM ameliorates depressive-like behavior by targeting miR-9 to regulate microglial activation via HSP90 ubiquitination

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