Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs

Li, Le; Stary, Creed M.

doi:10.1155/2016/6032306

Cited by 24 publications

(26 citation statements)

References 137 publications

(162 reference statements)

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“…Over the past decade, it has been confirmed by a number of studies that miRs serve an important role in the cellular response to ischemic injury ( 11 , 29 ). A recent study investigating the role of miRs in cerebral ischemia injury established that the miR-29 family is an important mediator in the assessment of brain injury and determining the prognosis of patients following stroke ( 30 ).…”

Section: Discussionmentioning

confidence: 98%

MicroRNA-29b alleviates oxygen and glucose deprivation/reperfusion-induced injury via inhibition of the p53‑dependent apoptosis pathway in N2a neuroblastoma cells

et al. 2017

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Cerebral ischemic injury causes severe brain damage and remains one of the leading causes of morbidity and mortality worldwide. Members of the microRNA-29 (miR-29) family are involved in regulating the process of ischemia and may be developed as biomarkers to diagnose and treat cerebral ischemia. The role of miR-29b in cerebral ischemia injury remains poorly understood. The purpose of the present study was to investigate whether miR-29b overexpression suppressed cerebral ischemic injury and to explore its underlying mechanism of action. The results demonstrated that levels of miR-29b in N2a neuroblastoma cells decreased following oxygen and glucose deprivation/reperfusion (OGD/R) treatment. Transfection with miR-29b mimics significantly increased cell viability, decreased lactate dehydrogenase (LDH) leakage, inhibited apoptosis by decreasing morphological changes occurring in the nuclei and reduced caspase-3 activity in OGD/R-treated N2a cells. Conversely, miR-29b inhibitors enhanced OGD/R-induced cytotoxicity and apoptosis. In addition, the miR-29b mimics blocked the increase in Bax and p53 expression and decreased Bcl-2 expression in OGD/R-treated N2a cells, whereas miR-29b inhibitors exacerbated the changes in the expression of these apoptosis-associated proteins caused by OGD/R. p53 knockdown using p53 small interfering RNA decreased cell viability and increased LDH leakage, reversing the improvements that the miR-29b mimics induced in damaged cells. Taken together, the results of the present study demonstrated that miR-29b attenuates ischemic injury by negatively regulating the p53-dependent apoptosis pathway and may therefore be a novel potential therapeutic target for treating ischemic stroke.

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Section: Discussionmentioning

confidence: 98%

MicroRNA-29b alleviates oxygen and glucose deprivation/reperfusion-induced injury via inhibition of the p53‑dependent apoptosis pathway in N2a neuroblastoma cells

et al. 2017

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“…Interestingly, miR-181a is reported to regulate inflammatory responses in monocyte/macrophage lineage cells, partly through downregulating inflammatory cytokines [ 41 ] and suppressing downstream signaling pathways involving PTEN [ 33 , 42 ]. MiR-181a is also reported to affect mitochondrial functions and tolerance induction by T cells [ 43 , 44 ]. On the other hand, miR-93 reportedly activates the PI3K/Akt pathway, inhibiting translation of upstream genes including PTEN and PHLPP2 [ 32 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study)

Jyonouchi

Geng

Streck

et al. 2017

J Neuroinflammation

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BackgroundMicroRNAs (miRNAs) play a major role in regulating immune responses at post-transcriptional levels. Previously, we have reported fluctuating interlukine-1ß (IL-1ß)/IL-10 ratios produced by peripheral blood monocytes (PBMo) in some patients with autism spectrum disorders (ASD). This study examined whether changes in miRNA expression by PBMo are associated with changes in IL-1ß/IL-10 ratios and how such changes are associated with ASD clinical features.MethodsmiRNA expression by purified PBMo from ASD subjects (N = 69) and non-ASD controls (N = 27) were determined by high-throughput sequencing. Cytokine production by PBMo in responses to stimuli of innate immunity, and behavioral symptoms [assessed by aberrant behavioral checklist (ABC)] were also evaluated at the same time of sample obtainment.ResultsAs a whole, there was no difference in miRNA expression between ASD and control non-ASD PBMo. However, when ASD cells were subdivided into 3 groups with high, normal, or low IL-1ß/IL-10 ratios as defined in the “Results” section, in comparison with the data obtained from non-ASD controls, we observed marked changes in miRNA expression. Namely, over 3-fold changes in expression of miR-181a, miR-93, miR-223, miR-342, and miR-1248 were observed in ASD PBMo with high or low IL-1ß/IL-10 ratios, but not in ASD PBMo with normal ratios. These miRNAs that had altered in expression are those closely associated with the regulation of key signaling pathways. With changes in IL-1ß/IL-10 ratios, we also observed changes in the production of cytokines (IL-6, TNF-α, and TGF-ß) other than IL-1ß/IL-10 by ASD PBMo. The association between behavioral symptoms and cytokine levels was different when ASD cells exhibit high/low IL-1ß/IL-10 ratios vs. when ASD cells exhibited normal ratios. Non-IgE-mediated food allergy was also observed at higher frequency in ASD subjects with high/low IL-1ß/IL-10 ratios than with normal ratios.ConclusionsChanges in cytokine profiles and miRNA expression by PBMo appear to be associated with changes in ASD behavioral symptoms. miRNAs that are altered in expression in ASD PBMo with high/low IL-1ß/IL-10 ratios are those associated with inflammatory responses. Changes in IL-1ß/IL-10 ratios along with changes in miRNA expression may serve as biomarkers for immune-mediated inflammation in ASD.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1003-6) contains supplementary material, which is available to authorized users.

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“…MicroRNAs (miRs) are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. MiRs regulate the microglial neuroinflammatory response and miR-targeted therapies were demonstrated to improve clinical outcome following adult cerebral ischemia in pre-clinical studies [ 81 , 82 , 83 , 84 ]. Findings of selective miRs involved in the inflammatory responses after acute HI/stroke in newborns boys and girls may further help the clinicians in neonatal intensive care units.…”

Section: Discussionmentioning

confidence: 99%

Sexually Dimorphic Outcomes after Neonatal Stroke and Hypoxia-Ischemia

Charriaut‐Marlangue

Besson

Baud

2017

IJMS

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Cohort studies have demonstrated a higher vulnerability in males towards ischemic and/or hypoxic-ischemic injury in infants born near- or full-term. Male sex was also associated with limited brain repair following neonatal stroke and hypoxia-ischemia, leading to increased incidence of long-term cognitive deficits compared to females with similar brain injury. As a result, the design of pre-clinical experiments considering sex as an important variable was supported and investigated because neuroprotective strategies to reduce brain injury demonstrated sexual dimorphism. While the mechanisms underlining these differences between boys and girls remain unclear, several biological processes are recognized to play a key role in long-term neurodevelopmental outcomes: gonadal hormones across developmental stages, vulnerability to oxidative stress, modulation of cell death, and regulation of microglial activation. This review summarizes the current evidence for sex differences in neonatal hypoxic-ischemic and/or ischemic brain injury, considering the major pathways known to be involved in cognitive and behavioral deficits associated with damages of the developing brain.

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Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs

Cited by 24 publications

References 137 publications

MicroRNA-29b alleviates oxygen and glucose deprivation/reperfusion-induced injury via inhibition of the p53‑dependent apoptosis pathway in N2a neuroblastoma cells

MicroRNA-29b alleviates oxygen and glucose deprivation/reperfusion-induced injury via inhibition of the p53‑dependent apoptosis pathway in N2a neuroblastoma cells

MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study)

Sexually Dimorphic Outcomes after Neonatal Stroke and Hypoxia-Ischemia

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