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.
Highlights
Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia, insulin resistance, and/or insulin deficiency [1]
Compared to the normal group, the expression of Long non-coding RNAs (lncRNAs) H19 was significantly increased in the empty vector model, negative control group (NC), and over-expressed lncRNA H19 groups, while it was decreased in the lncRNA H19-short hairpin RNA (shRNA) group (P < 0.05)
There was no significant difference between the lncRNA H19-shRNA and normal groups (P > 0.05)
Summary
Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia, insulin resistance, and/or insulin deficiency [1]. Animal models with DM exhibit biochemical and behavioral deficits, in the hippocampus, a brain region important for memory and learning [4]. Long non-coding RNAs (lncRNAs) are essential for higher cognitive abilities and brain development, and are involved in psychiatric diseases, providing tissue- and activity-specific epigenetic and transcriptional regulation [6]. The lncRNA H19 has been associated with the regulation of human tumor growth [10] and activation of the Wnt signaling pathway [11]. We hypothesized that lncRNA H19 might regulate apoptosis of hippocampal neurons via the Wnt signaling. Using a rat DM model, we investigated the impact of lncRNA H19 on learning and memory, apoptosis of hippocampal neurons, and involvement of the Wnt signaling
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