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Identification of miRNA expression associated with Alzheimer’s disease and neurodegeneration in rat models with obstructive sleep apnea

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Abstract

Background

Obstructive sleep apnea (OSA) is a common disorder that is associated with increased cerebrovascular disease and neurocognitive impairment. Although reports on cardiovascular and cerebrovascular morbidity have been conducted, there are few research on the mechanism related to cognitive decline and dementia especially, Alzheimer’s disease (AD). Recent study reinforces OSA-AD link with amyloid deposition in the OSA brain and APOE genotype prevalence in OSA. This study is designed to find a link between OSA and neurodegenerative with successful animal model setting.

Methods

A total of 16 rats were used, divided into the control and OSA group. For OSA, 0.3% cross-linked hyaluronic acid was injected twice every 12 weeks into the base of the tongue to create an OSA model. After 12 and 24 weeks, chronic OSA was identified with full channel polysomnography (PSG). The Morris water maze (MWM) test was conducted in control and OSA groups at 22 weeks, and pathological findings were subsequently confirmed 24 weeks after OSA induction. In addition, we studied the epigenetic changes with miRNA to identify the biomarkers for the prediction of dementia in OSA.

Results

In the MWM test, the speed of finding the platform was lower than that of the control group (47.0 ± 13.9 s; OSA group/12.4 ± 6.1 s; control, p < 0.01). In brain histopathologic changes, disorganized cortex layers in OSA group were prominent compared with the control cortex. Hippocampal cortex in OSA also showed a disorganized CA1 region with degenerative neurons and fibrillary changes, compared with the control. The miRNA analysis identified an up-regulation in MiR-132-5p/137-3p/137-5p/501-3p, also known as AD, and a down-regulation of MiR-182/183-3p/183-5p/200a-3p/200b-3p/21-5p.

Conclusion

OSA rat model with tongue hypertrophy showed neurodegenerative changes in brain and the epigenetic changes of mRNA/miRNA which have been known as AD-related genes.

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Acknowledgements

This study was carried out with the support of ‘R&D Program for Forest Science Technology (Project No. 2020196D10-2222-BA01, 2021389B10-2223-0102)’ provided by the Korea Forest Service (Korea Forestry Promotion Institute). This research was supported by “Regional Innovation Strategy (RIS)” through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (2022RIS-005).

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Authors and Affiliations

  1. Sleep Medicine Research Center, Department of Neurology, International St. Mary’s Hospital, Catholic Kwandong University, Incheon, 22711, Republic of Korea

    Hyeyun Kim

  2. Department of Pathology, International St. Mary’s Hospital, Catholic Kwandong University, Incheon, 22711, Republic of Korea

    Ju Yeon Pyo

  3. Department of Physiology, College of Medicine, Catholic Kwandong University, Gangneung, 25601, Republic of Korea

    Jiyeon Moon, Seungeun Lee, Minchae Kim, Yein Choi & Byong-Gon Park

  4. Department of Neurology, Chungbuk National University Hospital, Cheongju, 28644, Republic of Korea

    Dong-Ick Shin

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  1. Hyeyun Kim
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Correspondence to Dong-Ick Shin or Byong-Gon Park.

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Conflict of interest

Hyeyun Kim, Ju Yeon Pyo, Jiyeon Moon, Seungeun Lee, Minchae Kim, Yein Choi, Dong-Ick Shin4, Byong-Gon Park declares that they have no conflict of interest.

Ethical approval

This study was conducted under the supervision and approval of the Animal Ethics Committee for the maintenance and management of animals, and certain temperatures, humidity, diet, and water supply were conducted. All experiments were carried out in accordance with “Care and Use of Laboratory Animals” published by the US National Institutes of Health, and the study was approved by the Committee for the Care and Use of Laboratory Animals at Catholic Kwandong University (2019-006). Procedures, manufacturing, and sacrifice processes were carried out in compliance with the three R principles of animal study (replacement, reduction, and refinement).

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Kim, H., Pyo, J.Y., Moon, J. et al. Identification of miRNA expression associated with Alzheimer’s disease and neurodegeneration in rat models with obstructive sleep apnea. Mol. Cell. Toxicol. 19, 789–798 (2023). https://doi.org/10.1007/s13273-022-00309-y

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