Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
Ann Clin Transl Neurol. 2021 Jul;8(7):1408-1421. doi: 10.1002/acn3.51379. Epub 2021 May 28.
Stroke 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.
Expressions 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.
ARPP21 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.
ARPP21 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.
中风是一种脑血管疾病，常导致神经功能缺陷。ARPP21 是 miR-128 控制神经发育功能的保守宿主基因。本研究探讨了 ARPP21 拮抗内源性 miR-128 对中风后神经功能修复的机制。
检测中风患者中 ARPP21 和 miR-128 的表达。体外培养小鼠神经元和星形胶质细胞，并进行氧葡萄糖剥夺（OGD）处理。用 pc-ARPP21 和 miR-128 模拟物转染 OGD 处理的细胞。检测星形胶质细胞的增殖、神经元和星形胶质细胞的凋亡以及星形胶质细胞的炎症因子。验证 miR-128 与 CREB1 的结合关系。建立大脑中动脉闭塞（MCAO）大鼠模型。检测模型大鼠中 ARPP21 的表达。观察 pc-ARPP21 对大鼠神经元损伤、脑水肿体积和脑梗死的影响。
中风患者中 ARPP21 表达下调，miR-128 表达上调。pc-ARPP21 促进星形胶质细胞增殖，抑制神经元和星形胶质细胞凋亡，减少星形胶质细胞炎症。miR-128 模拟物可逆转 pc-ARPP21 对神经元和星形胶质细胞的这些作用。miR-128 靶向 CREB1 并减少 BDNF 分泌。体外实验证实 MCAO 大鼠 ARPP21 表达降低，pc-ARPP21 促进中风后神经功能修复。
ARPP21 通过拮抗 miR-128 上调 CREB1 和 BDNF 的表达，从而抑制神经元凋亡，促进中风后神经功能修复。本研究为中风的治疗提供了一个新的靶点。
