Inhibition of microRNA-10b-5p up-regulates HOXD10 to attenuate Alzheimer’s disease in rats via the Rho/ROCK signalling pathway

Abstract

Objective

It is believed that microRNAs (miRNAs) participate in the pathogenesis of Alzheimer’s disease (AD), but the specified function of miR-10b-5p in the disease has not been thoroughly understood. Thereafter, this research aimed to assess the function of miR-10b-5p in AD.

Methods

Rat AD models were established by injected with amyloid-β_1-42 (Aβ_1-42), which were mainly treated with lentivirus-miR-10b-5p inhibitor, or lentivirus-overexpressed homeobox D10 (HOXD10). MiR-10b-5p, HOXD10, RhoA, ROCK1 and ROCK2 expression in rat hippocampal tissues were determined. Afterwards, the behaviour of rats was tested, and neuronal apoptosis, pathological injury, and inflammatory factors and oxidative stress-related factors were all assessed. Finally, the target relation between miR-10b-5p and HOXD10 was detected.

Results

MiR-10b-5p was upregulated while HOXD10 was downregulated, and the Rho/ROCK signalling pathway was activated in hippocampal tissues of rats with AD. Inhibition of miR-10b-5p could attenuate the neuronal apoptosis, pathological injury, inflammation reaction, and oxidative stress by elevating HOXD10 and inhibiting the Rho/ROCK signalling pathway in AD rats. Moreover, HOXD10 was targeted by miR-10b-5p.

Conclusion

Inhibited miR-10b-5p decelerated the development of AD by promoting HOXD10 and inactivating the Rho/ROCK signalling pathway, and our findings may contribute to the exploration of AD treatment.

Keywords:

• Alzheimer’s disease
• microRNA-10b-5p
• homeobox D10
• the Rho/ROCK signalling pathway
• neuronal apoptosis
• pathological injury
• inflammation reaction
• oxidative stress

Acknowledgements

The authors acknowledge the reviewers for their helpful comments on this paper.

Disclosure statement

The authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by the Project of Hunan Provincial Health Committee [2,02,00,497], Scientific Research Fund Project of Hunan Provincial Health Commission (20200497) and Hengyang Science and Technology Plan Project (2020jh042748).