Retracted: Effects of microRNA‐10a on synapse remodeling in hippocampal neurons and neuronal cell proliferation and apoptosis through the BDNF‐TrkB signaling pathway in a rat model of Alzheimer's disease

Abstract

The aim of this study was to research the effects of microRNA-10a (miR-10a) on synapse remodeling and neuronal cells in rats with Alzheimer's disease (AD) through BDNF-TrkB signaling pathway. Rat models of AD were established. The neuronal cells were allocated into blank, negative control (NC), miR-10a mimics, miR-10a inhibitors, K252a, and miR-10a inhibitors + K252a groups. Expressions of miR-10a, p38, PSD95, BDNF, cAMP-response element-binding protein (CREB), and tropomyosin receptor kinase B (TrκB) were tested using RT-qPCR and Western blotting. Neuron cell proliferation, cycle, and apoptosis were observed using Cell counting kit-8 (CCK8) assay and flow cytometry. The ultrastructure was observed under a scanning electron microscope. The miR-10a expression of AD rats increased while p38, PSD95, BDNF, CREB, and TrκB expression decreased compared with the normal rats. Dual luciferase reporter gene assay testified miR-10a targeted BDNF. The expressions of p38, PSD95, BDNF, CREB, and TrκB decreased in the miR-10a mimics and K252a groups. Compared with the blank and NC group, the miR-10a mimics and K252a groups showed inhibited cell growth rate with cells mainly rest in the G1 satge, and increased spoptosis. The miR-10a inhibitors group presented an opposite trend to the miR-10a mimics and K252a groups. The synapse was complete and abundant in the miR-10a inhibitors group while disappeared in the miR-10a mimics and K252a groups. The results indicated that miR-10a restrains synapse remodeling and neuronal cell proliferation while promoting apoptosis in AD rats via inhibiting BDNF-TrkB signaling pathway.

Ethanol Extract of Oldenlandia diffusa Herba Attenuates Scopolamine-Induced Cognitive Impairments in Mice via Activation of BDNF, P-CREB and Inhibition of Acetylcholinesterase

“…The CREB is a key transcription factor, regulating synaptic and neural plasticity related genes [ 17 ]. According to We et al, the expression of BDNF is decreased in the AD rat model [ 18 ].…”

Applications of Acupuncture Therapy in Modulating the Plasticity of Neurodegenerative Disease and Depression: Do MicroRNA and Neurotrophin BDNF Shed Light on the Underlying Mechanism?

“…With regard to AD and its link with miRNAs and BDNF, the expression level of miR-132 was increased via BDNF regulation [ 93 , 94 ]. Furthermore, miR-322, miR-30a-5p, miR-206, miR-195, miR-10a, and miR-163 were identified to target BDNF [ 16 , 61 , 96 – 98 ]. Interestingly, EA improved learning and memory in AD rats, promoted neurogenesis in AD, and maintained hippocampal LTP to a certain extent.…”

“…Neuronal overexpression of miR-30a-5p resulted in downregulation of BDNF protein [ 61 ]. Another dual-luciferase reporter gene assay demonstrated that miR-10a targeted BDNF, and the authors indicated that miR-10a restrains synapse remodelling and neuronal cell proliferation while promoting apoptosis in AD rats by inhibiting the BDNF-TrkB signalling pathway [ 98 ]. Furthermore, miR-322 is significantly increased with the decrease in BDNF in the AD mouse brain, and a luciferase reporter assay identified that miR-322 can directly conjugate to the 3′-UTR of BDNF [ 16 ].…”

Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1

“…Recently, the role of altered miRNAs in the diagnosis for AD has been extensively studied. Several miRNAs have been shown to regulate AD-relative genes, such as amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1), and brain-derived neurotrophic factor (BDNF) [21][22][23] . This ability of selected miRNAs to target mRNAs which are altered in disease conditions makes them potential candidate as therapeutics or as targets of therapeutics.…”