Potential contribution of microRNA-125b targeting p38MAPK to relieving intermittent hypoxia-induced dementia of rat models

Abstract

Allowing for the correlation between intermittent hypoxia and impaired cognition, we intended to figure out whether and how dementia-relevant biomolecules (e.g. miR-125b and p38MAPK) might participate in weakening of intelligence in the context of intermittent hypoxia. Within this investigation, four groups of rat models were established, including rats treated with none, 10% continuous hypoxic (CH), 10% chronic intermittent hypoxia (CIH) and 5% chronic intermittent hypoxia (CIH). Moreover, the learning, memorizing and cognitive abilities of rats were evaluated through performing morris water maze, spatial navigation test and spatial probe test, respectively. Furthermore, expressions of miR-125b and p38MAPK were determined based on reverse transcription-polymerase chain reaction (RT-PCR) or western blotting. And the luciferase reporter gene assay was prepared to validate the targeted relationship between miR-125b and p38MAPK. Consequently, our study results showed that intermittent hypoxia generated more serious cognitive impairment to rats than persistent hypoxia (P < 0.05), and the rats treated with intermittent hypoxia were observed with down-regulated miR-125b expression and up-regulated phospho-p38MAPK expression (P < 0.05). Furthermore, the in-vitro tests exhibited that down-regulated expression of miR-125b and phosphorylation of p38MAPK could promote apoptosis of SH-SY5Y cells, and also depress their viability and proliferation (P < 0.05). The luciferase reporter gene assay also validated a targeted relationship between miR-125b and p38MAPK in SH-SY5Y cells. In conclusion, miR-125b targeting p38MAPK might be involved with modifying learning, memorizing and cognitive abilities of rats that were managed with intermittent hypoxia, which might provide theoretical basis for treating intermittent hypoxia-related dementia.

Keywords: Dementia; Intermittent hypoxia; MiR-125b; P38MAPK; Rat model; SH-SY5Y cell line.