MicroRNA-125b regulates microglia activation and motor neuron death in ALS

Parisi, Chiara; Napoli, Giulia; Amadio, Susanna; Spalloni, Alida; Apolloni, Savina; Longone, Patrizia; Volonté, Cinzia

doi:10.1038/cdd.2015.153

Cited by 110 publications

(104 citation statements)

References 60 publications

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“…There is growing evidence of the involvement of miRNA deregulation in ALS pathogenesis [207][208][209][210][211]. Changes in miRNA expression have been found in patients and the SOD1 G93A mouse [176,212,213] reflecting a dysfunction of the expressed RNA binding proteins involved in ALS.…”

Section: Microglia May Drive Als Pathophysiologymentioning

confidence: 99%

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Rodrı́guez¹,

Mahy²

2016

CMC

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Section: Microglia May Drive Als Pathophysiologymentioning

confidence: 99%

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Rodrı́guez¹,

Mahy²

2016

CMC

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“…Short messenger RNA (mRNA)-interfering molecules microRNAs (miRNAs) are recently identified as essential modulators of inflammatory response in the brain [8, 9]. Multifunctional miRNA miR-155 is among the miRNAs with expression profiles significantly affected by cerebral ischemia [10–12].…”

Section: Introductionmentioning

confidence: 99%

In vivo inhibition of miR-155 significantly alters post-stroke inflammatory response

Peña-Philippides

Caballero-Garrido

Lordkipanidze

et al. 2016

J Neuroinflammation

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BackgroundMicroRNA miR-155 is implicated in modulation of the inflammatory processes in various pathological conditions. In our previous studies, we demonstrated that in vivo inhibition of miR-155 promotes functional recovery after mouse experimental stroke. In the present study, we explored if this beneficial effect is associated with miR-155 inhibition-induced alterations in post-stroke inflammatory response.MethodsIntravenous injections of a specific miR-155 inhibitor were initiated at 48 h after mouse distal middle cerebral artery occlusion (dMCAO). Temporal changes in the expression of cytokines and key molecules associated with cytokine signaling were assessed at 7, 14, and 21 days after dMCAO, using mouse cytokine gene and protein arrays and Western blot analyses. Electron and immunofluorescence confocal microscopy techniques were used to evaluate the ultrastructural changes, as well as altered expression of specific phenotypic markers, at different time points after dMCAO.ResultsIn the inhibitor-injected mice (inhibitor group), there was a significant decrease in CCL12 and CXCL3 cytokine expression at 7 days and significantly increased levels of major cytokines IL-10, IL-4, IL-6, MIP-1α, IL-5, and IL-17 at 14 days after dMCAO. These temporal changes correlated with altered expression of miR-155 target proteins SOCS-1, SHIP-1, and C/EBP-β and phosphorylation levels of cytokine signaling regulator STAT-3. Electron microscopy showed decreased number of phagocytically active peri-vascular microglia/macrophages in the inhibitor samples. Immunofluorescence and Western blot of these samples demonstrated that expression of leukocyte/ macrophage marker CD45 and phagocytosis marker CD68 was reduced at 7 days, and in contrast, significantly increased at 14 days after dMCAO, as compared to controls.ConclusionsBased on our findings, we propose that in vivo miR-155 inhibition following mouse stroke significantly alters the time course of the expression of major cytokines and inflammation-associated molecules, which could influence inflammation process and tissue repair after experimental cerebral ischemia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0753-x) contains supplementary material, which is available to authorized users.

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“…For luciferase reporter assay, rat primary neurons in 24 well plates were stimulated for 12 h with CM when indicated, to neuronal apoptosis, which contributes to multiple CNS degenerative diseases [9,10].…”

Section: Luciferase Reporter Assaymentioning

confidence: 99%

ESE1 is Associated with Neuronal Apoptosis in Lipopolysaccharide Induced Neuroinflammation

Xue

Zhu

et al. 2016

Neurochem Res

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Neuronal apoptosis induced by the over-activation of microglia during neuroinflammation contributes to the pathology of central nervous system (CNS) degenerative diseases. ESE1 regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation. NF-κB activation participates in neuronal apoptosis. However, the expression and functions of ESE1 in neuronal apoptosis during CNS inflammatory response remain unclear. In present study, ESE1 expression significantly increased in cerebral cortex after lipopolysaccharide (LPS) intracerebroventricular injection. Immunofluorescence staining indicated that ESE1 was located in neurons. Furthermore, there was a concomitant up-regulation of apoptotic markers including active caspase-3, BAX and decreased expression of anti-apoptosis protein Bcl-2. In vitro, ESE1 depletion in cortical primary neurons inhibited active caspase-3 and BAX expression as well as lactate dehydrogenase (LDH) release with up-regulation of Bcl-2, while ESE1 overexpression can exert opposite effects, indicating that ESE1 promoted neuronal apoptosis induced by LPS or LPS exposed microglia conditioned media (CM). ESE1 accelerated NF-κB activation in neurons with CM treatment. Collectively, all these data suggested that ESE1 might boost neuronal apoptosis during neuroinflammation via up-regulating NF-κB activation. These findings have implications on the potential target of ESE1 in CNS inflammation treatment.

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MicroRNA-125b regulates microglia activation and motor neuron death in ALS

Cited by 110 publications

References 60 publications

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

In vivo inhibition of miR-155 significantly alters post-stroke inflammatory response

ESE1 is Associated with Neuronal Apoptosis in Lipopolysaccharide Induced Neuroinflammation

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