Morphine induces the apoptosis of mouse hippocampal neurons HT-22 through upregulating miR-181-5p

Abstract

Objective: To elucidate the role of morphine in inducing apoptosis of mouse hippocampal neurons HT-22 by upregulating microRNA-181-5p (miR-181-5p).

Materials and methods: After treatment of different doses of morphine, changes in proliferative ability, apoptosis, and expression levels of miR-181-5p and MAPK1 in HT-22 cells were assessed through a series of functional experiments. Regulatory effects of miR-181-5p on morphine-induced phenotype changes of HT-22 cells were examined. The interaction between miR-181-5p and MAPK1, and their involvement in morphine-induced neuron apoptosis were explored by Luciferase assay and rescue experiments, respectively.

Results: Morphine treatment markedly attenuated viability and proliferative ability in HT-22 cells, while apoptotic rate increased. MiR-181-5p was upregulated and MAPK1 was downregulated in HT-22 cells by morphine induction. Knockdown of miR-181-5p enhanced viability and proliferative ability, as well as reduced apoptosis in morphine-induced HT-22 cells. MiR-181-5p could specifically bind MAPK1 and negatively regulate its expression level. Knockdown of MAPK1 was able to reverse the regulatory effects of miR-181-5p on morphine-induced phenotype changes of HT-22 cells.

Conclusions: Morphine induces apoptosis of hippocampal neurons HT-22 by upregulating miR-181-5p to suppress the level of MAPK1.