Open Access

MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer's disease mice

  • Authors:
    • Fang‑Zhou Chen
    • Ying Zhao
    • Hui‑Zhao Chen
  • View Affiliations

  • Published online on: October 24, 2018     https://doi.org/10.3892/ijmm.2018.3957
  • Pages: 91-102
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disease that often occurs at a slow pace yet deteriorates with time. MicroRNAs (miRs) have been demonstrated to offer novel therapeutic hope for disease treatment. The aim of the present study was to investigate the effect of miR‑98 on amyloid β (Aβ)‑protein production, oxidative stress and mitochondrial dysfunction through the Notch signaling pathway by targeting hairy and enhancer of split (Hes)‑related with YRPW motif protein 2 (HEY2) in mice with AD. A total of 70 Kunming mice were obtained and subjected to behavioral assessment. The levels of oxidative stress‑related proteins glutathione peroxidase, reduced glutathione, superoxide dismutase, malondialdehyde, acetylcholinesterase and Na+‑K+‑ATP were measured. Morphological changes in brain tissue, HEY2‑positivity levels, neuronal apoptotic index (AI) and neuron mitochondrial DNA (mtDNA) levels were also determined. Subsequently, the levels of miR‑98 and the mRNA and protein levels of HEY2, Jagged1, Notch1, Hes1, Hes5, β‑amyloid precursor protein, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein in tissues and hippocampal neurons were determined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. Finally, hippocampal neuron viability and apoptosis were determined using an MTT assay and flow cytometry, respectively. The levels of miR‑98‑targeted HEY2 and miR‑98 were low and the levels of HEY2 were high in the AD mice. The AD mice exhibited poorer learning and memory abilities, oxidative stress function, and morphological changes of pyramidal cells in the hippocampal CA1 region. Furthermore, the AD mice exhibited increased protein levels of HEY2 and AI in the CA1 region of brain tissues with reduced mtDNA levels and dysfunctional neuronal mitochondria. miR‑98 suppressed hippocampal neuron apoptosis and promoted hippocampal neuron viability by inactivating the Notch signaling pathway via the inhibition of HEY2. In conclusion, the results demonstrated that miR‑98 reduced the production of Aβ and improved oxidative stress and mitochondrial dysfunction through activation of the Notch signaling pathway by binding to HEY2 in AD mice.
View Figures
View References

Related Articles

Journal Cover

January 2019
Volume 43 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Chen, F., Zhao, Y., & Chen, H. (2019). MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer's disease mice. International Journal of Molecular Medicine, 43, 91-102. https://doi.org/10.3892/ijmm.2018.3957
MLA
Chen, F., Zhao, Y., Chen, H."MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer's disease mice". International Journal of Molecular Medicine 43.1 (2019): 91-102.
Chicago
Chen, F., Zhao, Y., Chen, H."MicroRNA-98 reduces amyloid β-protein production and improves oxidative stress and mitochondrial dysfunction through the Notch signaling pathway via HEY2 in Alzheimer's disease mice". International Journal of Molecular Medicine 43, no. 1 (2019): 91-102. https://doi.org/10.3892/ijmm.2018.3957