Mechanism of ARPP21 antagonistic intron miR-128 on neurological function repair after stroke.

Abstract

ObjectiveStroke is a cerebrovascular disorder that often causes neurological function defects. ARPP21 is a conserved host gene of miR‐128 controlling neurodevelopmental functions. This study investigated the mechanism of ARPP21 antagonistic intron miR‐128 on neurological function repair after stroke.MethodsExpressions of ARPP21 and miR‐128 in stroke patients were detected. The mouse neurons and astrocytes were cultured in vitro and treated with oxygen–glucose deprivation (OGD). The OGD‐treated cells were transfected with pc‐ARPP21 and miR‐128 mimic. The proliferation of astrocytes, and the apoptosis of neurons and astrocytes were detected, and inflammatory factors of astrocytes were measured. The binding relationship between miR‐128 and CREB1 was verified. The rat model of middle cerebral artery occlusion (MCAO) was established. ARPP21 expression in model rats was detected. The effects of pc‐ARPP21 on neuron injury, brain edema volume, and cerebral infarct in rats were observed.ResultsARPP21 expression was downregulated and miR‐128 expression was upregulated in stroke patients. pc‐ARPP21 facilitated the proliferation of astrocytes and inhibited apoptosis of neurons and astrocytes, and reduced inflammation of astrocytes. miR‐128 mimic could reverse these effects of pc‐ARPP21 on neurons and astrocytes. miR‐128 targeted CREB1 and reduced BDNF secretion. In vitro experiments confirmed that ARPP21 expression was decreased in MCAO rats, and pc‐ARPP21 promoted neurological function repair after stroke.ConclusionARPP21 upregulated CREB1 and BDNF expressions by antagonizing miR‐128, thus inhibiting neuronal apoptosis and promoting neurological function repair after stroke. This study may offer a novel target for the management of stroke.