Long non-coding RNA H19 induces hippocampal neuronal apoptosis via Wnt signaling in a streptozotocin-induced rat model of diabetes mellitus

长链非编码 RNA H19 通过 Wnt 信号在链脲佐菌素诱发的糖尿病大鼠模型中诱导海马神经元凋亡

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作者:Yu-Hao Zhao, Tie-Feng Ji, Qi Luo, Jin-Lu Yu

Abstract

Defects in hippocampal synaptic plasticity and disorders of memory and learning are the central nervous system complications of diabetes mellitus (DM). Here, we used a streptozotocin-induced rat DM model to investigate the effects of long non-coding RNA H19 (lncRNA H19) on learning and memory and apoptosis of hippocampal neurons, and the involvement of the Wnt signaling. Our data demonstrate that lncRNA H19 is highly expressed in rats with DM. Over-expression of lncRNA H19 increased positioning navigation latency in DM rats and decreased duration of space exploration. lncRNA H19 over-expression also increased hippocampal neuronal apoptosis and expression of Wnt3, β-catenin, TCF-1, Bax, caspase-8 and caspase-3. By contrast, expression of GSK-3β and Bcl-2 was suppressed in DM rats over-expressing lncRNA H19. These results suggest that lncRNA H19 induces hippocampal neuronal apoptosis via Wnt signaling, and that inhibition of lncRNA H19 may serve as a promising novel target for the treatment of cognitive decline in patients with DM.

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