Dataset Information

MicroRNA-125a-3p is involved in early behavioral disorders in stroke-afflicted rats through the regulation of Cadm2.

ABSTRACT: Ischemic strokes carry a significant risk of mortality and recurrent vascular events. Recent studies suggest that changes in microRNAs (miRNAs or miRs) may affect the development of the stroke. However, few studies have investigated the role of miRNAs in behavioral disorder in early stroke. In the present study, animal models of middle cerebral artery occlusion (MCAO) are used, as well as a cell model of neurite outgrowth to further investigate the role of miRNAs in targeting synapse-associated proteins expression in early stroke. The authors used miRNA expression microarrays on RNA extracted from the cortex tissue samples from the rats of MCAO and control rats. Reverse transcription?quantitative polymerase chain reaction was conducted to verify the candidate miRNAs discovered by microarray analysis. Data indicated that miR?125a was significantly increased in the cortex of the model of MCAO, which were concomitant with that rats of MCAO at the same age displayed significant behavioral deficits. Bioinformatics analysis predicted the cell adhesion molecule 2 (Cadm2, mRNA) neurite outgrowth-associated protein is targeted by miR?125a. Overexpression of miR?125a reduced the level of Cadm2 expression in PC12 cell injury induced by free-serum. In contrast, inhibition of miR?125a using miR?125a inhibitors significantly resulted in higher levels of Cadm2 expression. In conclusion, miR?125a is involved in the behavioral disorder of animal models of MCAO by regulation of Cadm2.

SUBMITTER: Liu Y

PROVIDER: S-EPMC5716446 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-125a-3p is involved in early behavioral disorders in stroke-afflicted rats through the regulation of Cadm2.

Liu Yuqing Y Li Yunjun Y Ren Zhenxing Z Si Wenwen W Li Yiwei Y Wei Gang G Zhao Wenguang W Zhou Jianhong J Tian Yage Y Chen Dongfeng D

International journal of molecular medicine 20171010 6

Ischemic strokes carry a significant risk of mortality and recurrent vascular events. Recent studies suggest that changes in microRNAs (miRNAs or miRs) may affect the development of the stroke. However, few studies have investigated the role of miRNAs in behavioral disorder in early stroke. In the present study, animal models of middle cerebral artery occlusion (MCAO) are used, as well as a cell model of neurite outgrowth to further investigate the role of miRNAs in targeting synapse-associated ...[more]

PMID: 29039453

Similar Datasets

Project description:BackgroundNeuronal injury is considered a critical risk factor in the pathogenesis of most neurological and neuropsychiatric diseases. However, the underlying molecular mechanisms and identification of potential therapeutic targets for preventing neuronal injury associated with brain function remain largely uncharacterized. Therefore, identifying neural mechanisms would put new insights into the progression of this condition and provide novel therapeutic strategies for the treatment of these diseases.MethodsStereotactic injection of AAV virus was used to knock-down the miR-26a-3p within hippocampus of rats. Behavioral changes was detected by open field test (OFT), elevated plus maze (EPM), forced swim test (FST) and sucrose preference test (SPT). The inflammatory cytokines and related proteins were verified by real-time quantitative PCR, immunoblotting or immunofluorescence assay. Golgi staining and electron microscopy analysis was used to observe the dendritic spine, synapse and ultrastructural pathology. SB203580 (0.5 mg/kg) were administered daily to prevent p38 MAPK via an intraperitoneal (i.p.) injection. Finally, electrophysiological method was used to examine the synaptic transmission via whole-cell patch-clamp recording.ResultsHere, we showed that miR-26a-3p deficiency within hippocampal regions leads to the activation of microglia, increased level of pro-inflammatory cytokines and behavioral disorders in rats, effects which appear to be mediated by directly targeting the p38 mitogen-activated protein kinase (MAPK)-NF-κB signaling pathway. Specifically, we found that the enhanced glia-activation may consequently result in neuronal deterioration that mainly presented as the dysregulation of structural and functional plasticity in hippocampal neurons. In contrast, preventing p38 pathway by SB203580 significantly ameliorated abnormal behavioral phenotypes and neuronal jury resulting from miR-26a-3p knock-down.ConclusionThese results suggest that the normal expression of miR-26a-3p exerts neuroprotective effects via suppressing neural abnormality and maintaining neuroplasticity to against behavioral disorders in rats. These effects appear to involve a down-regulation of p38 MAPK-NF-κB signaling within the hippocampal region. Taken together, these findings provide evidence that miR-26a-3p can function as a critical factor in regulating neural activity and suggest that the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of neurological disorders.

Dataset Information

MicroRNA-125a-3p is involved in early behavioral disorders in stroke-afflicted rats through the regulation of Cadm2.

Publications

MicroRNA-125a-3p is involved in early behavioral disorders in stroke-afflicted rats through the regulation of Cadm2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets