Xichang Liu1, Haitao Wang2, Jiawei Bei3, Jun Zhao4, Ge Jiang5, Xiuhong Liu6. 1. Department of Neurology, Taizhou Hospital of Zhejiang Province Taizhou, Zhejiang Province, China. 2. Department of Neurology, Dongchangfu People's Hospital Liaocheng, Shandong Province, China. 3. Department of Internal Medicine, Hengshui Eight People's Hospital Hengshui, Hebei Province, China. 4. Department of Neurology, Laoling People's Hospital Dezhou, Shandong Province, China. 5. Department of Emergency, Penglai Traditional Chinese Medicine Hospital Yantai, Shandong Province, China. 6. Department of Brain Disease, Dezhou Traditional Chinese Medicine Hospital Dezhou, Shandong Province, China.
Abstract
OBJECTIVE: To explore the role and of miR-132, HMGA2 and PI3K/AKT pathway in mice with Alzheimer's disease (AD). METHODS: The mice were divided into 7 groups: the normal group, the model group (AD model mice), the NC group (AD mice injected with negative control (NC) vector), the miR-132 mimic group (AD mice injected with miR-132 mimics), the miR-132 inhibitor group (AD mice injected with miR-132 inhibitor), the si-HMGA2 group (AD mice injected with HMGA2 silencing vector), and the miR-132 inhibitor + si-HMGA2 group (model mice treated with miR-132 inhibitor and si-HMGA2). Y-maze experiment and related molecular biology experiments were performed. RESULTS: The double-luciferase reporter assay verified that miR-132 could target and inhibit the expression of HMGA2A. Compared with the NC group, model mice had decreased learning and memory ability, reduced miR-132, p-PI3K/PI3K, p-AKT/AKT, AQP4 expression as well as GFAP GSH-Px, SOD, ATP, and T-AOC levels, but increased expression of HMGA2 and the levels of TNF-α, IL-6, NO, IL-1β, MAO, and MDA (P<0.017). Up-regulation of miR-132 or silencing HMGA2 could partly reverse the changes, but inhibition of miR-132 would exaggerate the brain injury and these molecular changes (P<0.017). The combination uses of si-HMGA2 and miR-132 inhibitor could reverse the changes caused by miR-132 inhibitor (P<0.017). CONCLUSION: miR-132 could downregulate the expression of HMGA2 and promote the expression of the PI3K/AKT pathway, so as to achieve a protective effect on brain in AD mice. AJTR
OBJECTIVE: To explore the role and of miR-132, HMGA2 and PI3K/AKT pathway in mice with Alzheimer's disease (AD). METHODS: The mice were divided into 7 groups: the normal group, the model group (AD model mice), the NC group (AD mice injected with negative control (NC) vector), the miR-132 mimic group (AD mice injected with miR-132 mimics), the miR-132 inhibitor group (AD mice injected with miR-132 inhibitor), the si-HMGA2 group (AD mice injected with HMGA2 silencing vector), and the miR-132 inhibitor + si-HMGA2 group (model mice treated with miR-132 inhibitor and si-HMGA2). Y-maze experiment and related molecular biology experiments were performed. RESULTS: The double-luciferase reporter assay verified that miR-132 could target and inhibit the expression of HMGA2A. Compared with the NC group, model mice had decreased learning and memory ability, reduced miR-132, p-PI3K/PI3K, p-AKT/AKT, AQP4 expression as well as GFAP GSH-Px, SOD, ATP, and T-AOC levels, but increased expression of HMGA2 and the levels of TNF-α, IL-6, NO, IL-1β, MAO, and MDA (P<0.017). Up-regulation of miR-132 or silencing HMGA2 could partly reverse the changes, but inhibition of miR-132 would exaggerate the brain injury and these molecular changes (P<0.017). The combination uses of si-HMGA2 and miR-132 inhibitor could reverse the changes caused by miR-132 inhibitor (P<0.017). CONCLUSION:miR-132 could downregulate the expression of HMGA2 and promote the expression of the PI3K/AKT pathway, so as to achieve a protective effect on brain in AD mice. AJTR
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