Circular RNA circEfnb2 promotes cell injury after cerebral infarction by sponging miR-202-5p and regulating TRAF3 expression.

BACKGROUND: Exogenous neural cell transplantation may be therapeutic for stroke, cerebral ischemic injury. Among other mechanisms, increasing findings indicated circular RNAs (circRNAs) regulate the pathogenesis progression of cerebral ischemia. Mmu_circ_0015034 (circEfnb2) was upregulated in focal cortical infarction established by middle cerebral artery occlusion (MCAO) in mice. Our study was designed to probe the molecular mechanism of circEfnb2 in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal damage in cerebral ischemia. METHODS: We established an in vitro OGD/R cell model. CircEfnb2 and microRNA-202-5p (miR-202-5p) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were assessed using specific kits. Tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß) levels were examined using an Enzyme-linked immunosorbent assay (ELISA). Flow cytometry analysis evaluated cell apoptosis. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cleaved caspase 3, and Tumor necrosis factor receptor-associated factor 3 (TRAF3) were determined using Western blot assay. RESULTS: Overall, circEfnb2 was highly expressed whereas miR-202-5p was decreased in OGD/R-treated mouse hippocampal neuronal HT22 cells compared to normal controls (both p > 0.05). From an in vitro functional perspective, circEfnb2 knockdown attenuated an OGD/R-triggered neuronal injury compared to controls (p > 0.05). Mechanically, circEfnb2 acted as a sponge of miR-202-5p; downregulation of miR-202-5p annulled the inhibitory roles of circEfnb2 silencing in an OGD/R-caused neuronal injury model. Our analysis showed that miR-202-5p directly targeted TRAF3 as enhanced TRAF3 abolished the effects of miR-202-5p in the OGD/R-induced neuronal injury. In vivo, lentivirus with a short hairpin (sh)-circEfnb2 inhibited cerebral injury, when injected into cerebral cortex in MCAO mice (p > 0.05). CONCLUSION: Our results suggest that circEfnb2 deficiency may decrease OGD/R-induced HT22 cell damage by modulating the miR-202-5p/TRAF3 axis. This explanation may provide a new direction for cerebral infarction potential therapeutic targets.

Alzheimer's disease, a metabolic disorder: Clinical advances and basic model studies (Review).

Alzheimer's disease (AD) is a type of neurodegenerative disease characterized by cognitive impairment that is aggravated with age. The pathological manifestations include extracellular amyloid deposition, intracellular neurofibrillary tangles and loss of neurons. As the world population ages, the incidence of AD continues to increase, not only posing a significant threat to the well-being and health of individuals but also bringing a heavy burden to the social economy. There is epidemiological evidence suggesting a link between AD and metabolic diseases, which share pathological similarities. This potential link would deserve further consideration; however, the pathogenesis and therapeutic efficacy of AD remain to be further explored. The complex pathogenesis and pathological changes of AD pose a great challenge to the choice of experimental animal models. To understand the role of metabolic diseases in the development of AD and the potential use of drugs for metabolic diseases, the present article reviews the research progress of the comorbidity of AD with diabetes, obesity and hypercholesterolemia, and summarizes the different roles of animal models in the study of AD to provide references for researchers.