ppanPersonalized Psychiatry and NeurologyPersonalized Psychiatry and Neurology2712-9179V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology of the Ministry of Health of the Russian Federation (Bekhterev NMRC PN)10.52667/2712-9179-2025-5-4-3-15ppan-145Research ArticleREVIEWThe Role of MicroRNAs as Crucial Regulators of Sleep /Wakefulness in Neurological and Mental Disorders (Systematic Review)SeitkazinaKamila

191014 St. Petersburg

kamilaserikovna@yandex.ruMariinsky HospitalRussian Federation20252412202554315Copyright © Seitkazina K., 20252025Seitkazina K.Seitkazina K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jppn.ru/jour/article/view/145

Sleep quality disorders in patients with neurological diseases are a common comorbid pathology that leads to mutual aggravation syndromes, accelerating the progression and severity of neurological conditions. Sleep problems speed up the progression of neurological diseases. In turn, these diseases further reduce sleep quality, this creates a “vicious cycle”. The prediction and early diagnosis of sleep quality disorders in patients with neurological profiles require the development of new sensitive and specific biomarkers. Among them, microRNA patterns are the most promising. This report will present the results of preclinical and clinical studies on changes in microRNA expression and their association with sleep quality disorders in experimental animals and humans with various neurological diseases and mental disorders. Additionally, a new personalized approach to assessing the risk of sleep quality disorders in patients with neurological and psychiatric profiles will be presented. This approach evaluates the risk of sleep disorders (low, medium, or high) based on the most thoroughly studied microRNA patterns.

sleep disorderneurodegenerative diseasemental disorderepigenetic biomarkermicroRNAReferencesPavlova, M.K.; Latreille, V. Sleep disorders. The American Journal of Medicine. 2019; 132(3):292-299. https://doi.org/10.1016/j.amjmed.2018.09.021.Pavlova, M.K.; Latreille, V. Sleep disorders. The American Journal of Medicine. 2019; 132(3):292-299. https://doi.org/10.1016/j.amjmed.2018.09.021.Gauld, C.; Lopez, R.; Morin, C. Symptom network analysis of the sleep disorders diagnostic criteria based on the clinical text of the ICSD‐3. Journal of Sleep Research. 2022; 31(1):e13435. https://doi.org/10.1111/jsr.13435.Gauld, C.; Lopez, R.; Morin, C. Symptom network analysis of the sleep disorders diagnostic criteria based on the clinical text of the ICSD‐3. Journal of Sleep Research. 2022; 31(1):e13435. https://doi.org/10.1111/jsr.13435.Perez, M.N.; Salas, R.M.E. Insomnia. CONTINUUM: Lifelong Learning in Neurology. 2020; 26(4):1003-1015. https://doi.org/10.1212/CON.0000000000000879.Perez, M.N.; Salas, R.M.E. Insomnia. CONTINUUM: Lifelong Learning in Neurology. 2020; 26(4):1003-1015. https://doi.org/10.1212/CON.0000000000000879.Karnaukhov, V.E.; Narodova, E.A.; Shnayder, N.A. Role of essential amino acid tryptophan in causing sleep disorders and anxiety-depressive disorders. Humans and Their Health. 2022; 25(2):13-23. https://doi.org/10.21626/vestnik/2022-2/02.Karnaukhov, V.E.; Narodova, E.A.; Shnayder, N.A. Role of essential amino acid tryptophan in causing sleep disorders and anxiety-depressive disorders. Humans and Their Health. 2022; 25(2):13-23. https://doi.org/10.21626/vestnik/2022-2/02.Kinoshita, C.; Okamoto, Y.; Aoyama, K.; Nakaki, T. MicroRNA: a key player for the interplay of circadian rhythm ab-normalities, sleep disorders and neurodegenerative diseases. Clocks & Sleep. 2020; 2(3):282-307. https://doi.org/10.3390/clockssleep2030022.Kinoshita, C.; Okamoto, Y.; Aoyama, K.; Nakaki, T. MicroRNA: a key player for the interplay of circadian rhythm ab-normalities, sleep disorders and neurodegenerative diseases. Clocks & Sleep. 2020; 2(3):282-307. https://doi.org/10.3390/clockssleep2030022.Nguyen, T.P.N.; Kumar, M.; Fedele? E. MicroRNA alteration, application as biomarkers, and therapeutic approaches in neurodegenerative diseases. International Journal of Molecular Sciences. 2022; 23(9):4718. https://doi.org/10.3390/ijms23094718.Nguyen, T.P.N.; Kumar, M.; Fedele? E. MicroRNA alteration, application as biomarkers, and therapeutic approaches in neurodegenerative diseases. International Journal of Molecular Sciences. 2022; 23(9):4718. https://doi.org/10.3390/ijms23094718.Khalyfa, A; Sanz-Rubio, D. Genetics and extracellular vesicles of pediatrics sleep disordered breathing and epilepsy. In-ternational Journal of Molecular Sciences. 2019; 20(21):5483. https://doi.org/10.3390/ijms20215483.Khalyfa, A; Sanz-Rubio, D. Genetics and extracellular vesicles of pediatrics sleep disordered breathing and epilepsy. In-ternational Journal of Molecular Sciences. 2019; 20(21):5483. https://doi.org/10.3390/ijms20215483.Konovalova, J.; Gerasymchuk, D.; Parkkinen, I. Interplay between microRNAs and oxidative stress in neurodegenerative diseases. International Journal of Molecular Sciences. 2019; 20(23):6055. https://doi.org/10.3390/ijms20236055.Konovalova, J.; Gerasymchuk, D.; Parkkinen, I. Interplay between microRNAs and oxidative stress in neurodegenerative diseases. International Journal of Molecular Sciences. 2019; 20(23):6055. https://doi.org/10.3390/ijms20236055.Gulia, K.K.; Kumar, V.M. Sleep disorders in the elderly: a growing challenge. Psychogeriatrics. 2018; 18(3):155-165. https://doi.org/10.1111/psyg.12319.Gulia, K.K.; Kumar, V.M. Sleep disorders in the elderly: a growing challenge. Psychogeriatrics. 2018; 18(3):155-165. https://doi.org/10.1111/psyg.12319.Zou, H.; Zhou, H.; Yan, R. Chronotype, circadian rhythm, and psychiatric disorders: Recent evidence and potential mechanisms. Frontiers in Neuroscience. 2022; 16:811771. https://doi.org/10.3389/fnins.2022.811771.Zou, H.; Zhou, H.; Yan, R. Chronotype, circadian rhythm, and psychiatric disorders: Recent evidence and potential mechanisms. Frontiers in Neuroscience. 2022; 16:811771. https://doi.org/10.3389/fnins.2022.811771.Ahangarpour, A.; Belali, R. Role of MicroRNAs in the Regulation of Sleep/wakefulness and Their Expression Changes in the Brain Following Sleep Deprivation. Jundishapur Journal of Physiology. 2024; 2(2):e148771. https://doi.org/10.3295/JJP.2023.2.2.121.Ahangarpour, A.; Belali, R. Role of MicroRNAs in the Regulation of Sleep/wakefulness and Their Expression Changes in the Brain Following Sleep Deprivation. Jundishapur Journal of Physiology. 2024; 2(2):e148771. https://doi.org/10.3295/JJP.2023.2.2.121.Holm, A.; Possovre, M.-L.; Bandarabadi, M. The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio. Proceedings of the National Academy of Sciences of the United States of America. 2022; 119(17):e2112225119. https://doi.org/10.1073/pnas.2112225119.Holm, A.; Possovre, M.-L.; Bandarabadi, M. The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio. Proceedings of the National Academy of Sciences of the United States of America. 2022; 119(17):e2112225119. https://doi.org/10.1073/pnas.2112225119.Yoshida, Y.; Yajima, Y.; Fujikura, Y. Identification of salivary microRNA profiles in male mouse model of chronic sleep disorder. Stress. 2023; 26(1):21-28. https://doi.org/10.1080/10253890.2022.2156783.Yoshida, Y.; Yajima, Y.; Fujikura, Y. Identification of salivary microRNA profiles in male mouse model of chronic sleep disorder. Stress. 2023; 26(1):21-28. https://doi.org/10.1080/10253890.2022.2156783.Wang, Y.; Lv K.; Chen H.; et al. Functional annotation of extensively and divergently expressed miRNAs in suprachias-matic nucleus of Clock Δ19 mutant mice. Bioscience Reports. 2018; 38(6): BSR20180233. https://doi.org/10.1042/BSR20180233.Wang, Y.; Lv K.; Chen H.; et al. Functional annotation of extensively and divergently expressed miRNAs in suprachias-matic nucleus of Clock Δ19 mutant mice. Bioscience Reports. 2018; 38(6): BSR20180233. https://doi.org/10.1042/BSR20180233.Linnstaedt, S.D.; Lv, K.; Chen, H. MicroRNA-19b predicts widespread pain and posttraumatic stress symptom risk in a sex-dependent manner following trauma exposure. Pain. 2020. 161(1):47-60. https://doi.org/10.1097/j.pain.0000000000001709.Linnstaedt, S.D.; Lv, K.; Chen, H. MicroRNA-19b predicts widespread pain and posttraumatic stress symptom risk in a sex-dependent manner following trauma exposure. Pain. 2020. 161(1):47-60. https://doi.org/10.1097/j.pain.0000000000001709.Lyons, L.C.; Vanrobaeys, Y.; Abel, T. Sleep and memory: The impact of sleep deprivation on transcription, translational control, and protein synthesis in the brain. Journal of Neurochemistry. 2023; 166(1):24-46. https://doi.org/10.1111/jnc.15787.Lyons, L.C.; Vanrobaeys, Y.; Abel, T. Sleep and memory: The impact of sleep deprivation on transcription, translational control, and protein synthesis in the brain. Journal of Neurochemistry. 2023; 166(1):24-46. https://doi.org/10.1111/jnc.15787.Karabulut, S.; Bayramov, K.; Bayramov, R. Effects of post-learning REM sleep deprivation on hippocampal plastici-ty-related genes and microRNA in mice. Behavioural Brain Research. 2019; 361:7-13. https://doi.org/10.1016/j.bbr.2018.12.045.Karabulut, S.; Bayramov, K.; Bayramov, R. Effects of post-learning REM sleep deprivation on hippocampal plastici-ty-related genes and microRNA in mice. Behavioural Brain Research. 2019; 361:7-13. https://doi.org/10.1016/j.bbr.2018.12.045.Kim, J.Y.; Kim, W.; Lee, K.-H. The role of microRNAs in the molecular link between circadian rhythm and autism spectrum disorder. Animal Cells and Systems. 2023; 27(1):38-52. https://doi.org/10.1080/19768354.2023.2180535.Kim, J.Y.; Kim, W.; Lee, K.-H. The role of microRNAs in the molecular link between circadian rhythm and autism spectrum disorder. Animal Cells and Systems. 2023; 27(1):38-52. https://doi.org/10.1080/19768354.2023.2180535.Qiu, J.; Zhang, J.; Zhou, Y. MicroRNA-7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland. Journal of Pineal Research. 2019; 66(3):e12552. https://doi.org/10.1111/jpi.12552.Qiu, J.; Zhang, J.; Zhou, Y. MicroRNA-7 inhibits melatonin synthesis by acting as a linking molecule between leptin and norepinephrine signaling pathways in pig pineal gland. Journal of Pineal Research. 2019; 66(3):e12552. https://doi.org/10.1111/jpi.12552.Ma, Q.; Mo, G.; Tan, Y. MicroRNAs and the biological clock: a target for diseases associated with a loss of circadian regu-lation. African Health Sciences. 2020; 20(4):1887-1894. https://doi.org/10.4314/ahs.v20i4.46.Ma, Q.; Mo, G.; Tan, Y. MicroRNAs and the biological clock: a target for diseases associated with a loss of circadian regu-lation. African Health Sciences. 2020; 20(4):1887-1894. https://doi.org/10.4314/ahs.v20i4.46.Soto, M.; Iranzo, A.; Lahoz, S. Serum microRNAs predict isolated rapid eye movement sleep behavior disorder and Lewy body diseases. Movement Disorders. 2022; 37(10):2086-2098. https://doi.org/10.1002/mds.29171.Soto, M.; Iranzo, A.; Lahoz, S. Serum microRNAs predict isolated rapid eye movement sleep behavior disorder and Lewy body diseases. Movement Disorders. 2022; 37(10):2086-2098. https://doi.org/10.1002/mds.29171.Weigend, S.; Holst, S.C.; Meier, J. Prolonged waking and recovery sleep affect the serum microRNA expression profile in humans. Clocks & Sleep. 2018; 1(1):75-86. https://doi.org/10.3390/clockssleep1010008.Weigend, S.; Holst, S.C.; Meier, J. Prolonged waking and recovery sleep affect the serum microRNA expression profile in humans. Clocks & Sleep. 2018; 1(1):75-86. https://doi.org/10.3390/clockssleep1010008.Knarr, M.; Nagaraj, A.B.; Kwiatkowski, L.J.; DiFeo, A. miR-181a modulates circadian rhythm in immortalized bone mar-row and adipose derived stromal cells and promotes differentiation through the regulation of PER3. Scientific Reports. 2019; 9(1):307. https://doi.org/10.1038/s41598-018-36425-w.Knarr, M.; Nagaraj, A.B.; Kwiatkowski, L.J.; DiFeo, A. miR-181a modulates circadian rhythm in immortalized bone mar-row and adipose derived stromal cells and promotes differentiation through the regulation of PER3. Scientific Reports. 2019; 9(1):307. https://doi.org/10.1038/s41598-018-36425-w.Chinnapaiyan, S.; Dutta, R.K.; Devadoss, D. Role of Non-Coding RNAs in Lung Circadian Clock Related Diseases. Inter-national Journal of Molecular Sciences. 2020; 21(8):3013. DOI: 10.3390/ijms21083013.Chinnapaiyan, S.; Dutta, R.K.; Devadoss, D. Role of Non-Coding RNAs in Lung Circadian Clock Related Diseases. Inter-national Journal of Molecular Sciences. 2020; 21(8):3013. DOI: 10.3390/ijms21083013.Yoshida, Y.; Yajima, Y.; Fujikura, Y. Identification of salivary microRNA profiles in male mouse model of chronic sleep disorder. Stress. 2023; 26(1):21-28. https://doi.org/10.1080/10253890.2022.2156783.Yoshida, Y.; Yajima, Y.; Fujikura, Y. Identification of salivary microRNA profiles in male mouse model of chronic sleep disorder. Stress. 2023; 26(1):21-28. https://doi.org/10.1080/10253890.2022.2156783.Alamdari, A.F.; Rahnemayan, S.; Rajabi, H. Melatonin as a promising modulator of aging related neurodegenerative dis-orders: Role of microRNAs. Pharmacological Research. 2021; 173:105839. https://doi.org/10.1016/j.phrs.2021.105839.Alamdari, A.F.; Rahnemayan, S.; Rajabi, H. Melatonin as a promising modulator of aging related neurodegenerative dis-orders: Role of microRNAs. Pharmacological Research. 2021; 173:105839. https://doi.org/10.1016/j.phrs.2021.105839.Moskaleva, P.V.; Shnayder, N.A.; Nasyrova, R.F. Association of polymorphic variants of DDC (AADC), AANAT and ASMT genes encoding enzymes for melatonin synthesis with the higher risk of neuropsychiatric disorders. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2021; 121(5):151. https://doi.org/10.17116/jnevro2021121041151.Moskaleva, P.V.; Shnayder, N.A.; Nasyrova, R.F. Association of polymorphic variants of DDC (AADC), AANAT and ASMT genes encoding enzymes for melatonin synthesis with the higher risk of neuropsychiatric disorders. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2021; 121(5):151. https://doi.org/10.17116/jnevro2021121041151.Mustafin, R.N.; Khusnutdinova, E.K. Epigenetic hypothesis of the role of peptides in aging. Advances in Gerontology. 2018; 31(1):10-20.Mustafin, R.N.; Khusnutdinova, E.K. Epigenetic hypothesis of the role of peptides in aging. Advances in Gerontology. 2018; 31(1):10-20.Hicks, S.D.; Khurana, N.; Williams, J. Diurnal oscillations in human salivary microRNA and microbial transcription: Im-plications for human health and disease. PLOS ONE. 2018; 13(7):e0198288. https://doi.org/10.1371/journal.pone.0198288.Hicks, S.D.; Khurana, N.; Williams, J. Diurnal oscillations in human salivary microRNA and microbial transcription: Im-plications for human health and disease. PLOS ONE. 2018; 13(7):e0198288. https://doi.org/10.1371/journal.pone.0198288.Liang, Y.; Wang, L. Inflamma-microRNAs in Alzheimer’s disease: From disease pathogenesis to therapeutic potentials. Frontiers in Cellular Neuroscience. 2021; 15:785433. https://doi.org/10.3389/fncel.2021.785433.Liang, Y.; Wang, L. Inflamma-microRNAs in Alzheimer’s disease: From disease pathogenesis to therapeutic potentials. Frontiers in Cellular Neuroscience. 2021; 15:785433. https://doi.org/10.3389/fncel.2021.785433.Hijmans, J.G.; Levy, M.; Garcia, V. Insufficient sleep is associated with a pro‐atherogenic circulating microRNA signature. Experimental Physiology. 2019; 104(6):975-982. https://doi.org/10.1113/EP087469.Hijmans, J.G.; Levy, M.; Garcia, V. Insufficient sleep is associated with a pro‐atherogenic circulating microRNA signature. Experimental Physiology. 2019; 104(6):975-982. https://doi.org/10.1113/EP087469.Baek, S.-J.; Ban, H.-J.; Park, S.-M. Circulating microRNAs as potential diagnostic biomarkers for poor sleep quality. Nature and Science of Sleep. – 2021; 13:1001-1012. https://doi.org/10.2147/NSS.S311541.Baek, S.-J.; Ban, H.-J.; Park, S.-M. Circulating microRNAs as potential diagnostic biomarkers for poor sleep quality. Nature and Science of Sleep. – 2021; 13:1001-1012. https://doi.org/10.2147/NSS.S311541.Sağır, F.; Ersoy Tunalı, Tombul, T. MiR-132-3p, miR-106b-5p, and miR-19b-3p are associated with brain-derived neu-rotrophic factor production and clinical activity in multiple sclerosis: A pilot study. Genetic Testing and Molecular Biomarkers. 2021; 25(11):720-726. https://doi.org/10.1089/gtmb.2021.0183.Sağır, F.; Ersoy Tunalı, Tombul, T. MiR-132-3p, miR-106b-5p, and miR-19b-3p are associated with brain-derived neu-rotrophic factor production and clinical activity in multiple sclerosis: A pilot study. Genetic Testing and Molecular Biomarkers. 2021; 25(11):720-726. https://doi.org/10.1089/gtmb.2021.0183.

The authors declare that there are no conflicts of interest present.