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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

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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

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Project description:BackgroundMany studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment.Methods237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls.ResultsDysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA.ConclusionsThis profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients.

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.

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