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Vol. 64 No. 15: Issue 15

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miR-22 exerts anti-alzheimic effects via the regulation of apoptosis of hippocampal neurons

https://doi.org/10.14715/10.14715/cmb/2017.64.15.14
Yu Wang
Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
Lan Zhao
Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
Bohong Kan
Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
Huiyan Shi
Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
Jingxian Han
Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China

Corresponding Author(s) : Jingxian Han

dr1308@163.com

Cellular and Molecular Biology, Vol. 64 No. 15: Issue 15

Abstract

To investigate the expression of miR-22 in the hippocampus of amyloid β (1-42)-induced alzheimic rats, and to assess the underlying mechanism. A total of 60 male Sprague Dawley rats weighing between 274.65 and 293.97 g (mean weight = 284.31 ± 9.66 g) and aged 12 to 14 weeks were randomly assigned to three groups: control group (n = 20), Alzheimer's disease group (AD group; n = 20) and AD + miR-22 mimic group (ADMM group; n = 22). Rat AD model was established by injecting a solution of Aβ1-42 into the hippocampal CA1 regions. After 24 h, rats in the ADMM group also received intraventricular injection of miR-22 mimic continuously for 28 days. The escape latency of rats, neuronal damage in the hippocampus, synaptic structure, brain-derived neurotrophic factor (BDNF), and the expressions of apoptosis-related proteins were assessed or determined, as appropriate. The expression of miR-22 in hippocampus of the AD group was significantly lower than that in the control group (p < 0.05). However, after 28 days of intraventricular injection of miR-22 mimic into AD rats, the expression was significantly increased, relative to control (p < 0.05). The escape latency of AD rats was significantly prolonged, and the number of platform sites significantly reduced when compared to the control group (p < 0.05). However, the escape latency was significantly shortened and the number of platform sites significantly increased in the ADMM group, relative to the control and AD groups. Results of transmission electron microscopy showed that the expression of miR-22 significantly reversed the degradation of synaptic structures in the hippocampus of AD rats as evidenced by recovery of abnormal synaptic cleft width and the length of synaptic active zones (p < 0.05). Results of Nissl staining revealed significant proliferation of gliacyte and loss of Nissl bodies. After miR-22 injection, the number of gliacytes in the hippocampus of AD rats was significantly reduced, while the number of Nissl bodies was significantly increased (p < 0.05). The expressions of BDNF in CA1 and CA2/3 regions of AD rats were significantly lower than those in the control group, and BDNF in the hippocampus of AD rats was significantly increased after 28 days of continuous injection of miR-22 (p < 0.05). The positive expression of Tunnel in the ADMM group (22.67 ± 2.96 %) was significantly higher than that in the AD group (4.49 ± 1.23 %), but significantly lower than that of control (39.51 ± 3.66 %) (p < 0.05). After 28 days of intraventricular injection of miR-22 mimic into AD rats, the expression of Bax protein was significantly down-regulated, while bcl-2 protein was significantly up-regulated (p < 0.05). The expression of miR-22 in the hippocampus of patients with AD inhibits neuronal apoptosis, thereby improving learning and memory dysfunction.

Keywords

MiR-22 Alzheimer's disease Hippocampal neurons Apoptosis Expression.
Wang, Y., Zhao, L., Kan, B., Shi, H., & Han, J. (2018). miR-22 exerts anti-alzheimic effects via the regulation of apoptosis of hippocampal neurons. Cellular and Molecular Biology, 64(15), 84–89. https://doi.org/10.14715/10.14715/cmb/2017.64.15.14
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References
  1. Jack CR, Bennett DA, Blennow K. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement 2018; 14: 535.
  2. Alaa AM, Yoon J, Hu S, van der Schaar M. Personalized Risk Scoring for Critical Care Prognosis Using Mixtures of Gaussian Processes. IEEE Trans Biomed Eng 2018; 65: 207-218.
  3. Harrison P. Alzheimer's disease and chromosome 14: Different gene, same process? British J Psychiatr 2018; 163: 2-5.
  4. Cope TE, Rittman T, Borchert RJ, Jones PS, Vatansever D, Allinson K. Tau burden and the functional connectome in Alzheimer's disease and progressive supranuclear palsy. Brain 2018; 141: 550-567.
  5. Idda ML, Munk R, Abdelmohsen K, Gorospe M. Noncoding RNAs in Alzheimer's disease. Wiley Interdiscip Rev RNA 2018; 9: 1463.
  6. Ross SP, Baker KE, Fisher A, Hoff L, Pak ES, Murashov AK. MiRNA-431 prevents amyloid-β-induced synapse loss in neuronal cell culture model of Alzheimer's Disease by silencing Kremen1. Front Cell Neurosci 2018; 12: 87.
  7. Zhao Y, Lukiw WJ. Microbiome-mediated upregulation of microRNA-146a in sporadic Alzheimer's Disease. Front Neurol 2018; 9: 145.
  8. Meng YC, Ding ZY, Wang HQ, Ning LP, Wang C. Effect of microRNA-155 on angiogenesis after cerebral infarction of rats through AT1R/VEGFR2 pathway. Asian Pac J Trop Med 2015; 8: 829-835.
  9. Zhao WJ, Zhang HF, Su JY. Downregulation of microRNA-195 promotes angiogenesis induced by cerebral infarction via targeting VEGFA. Mol Med Rep 2017; 16: 5434-5440.
  10. Absalon S, Kochanek DM, Raghavan V, Krichevsky AM. MiR-26b upregulated in Alzheimer's Disease activates cell cycle entry, Tau phosphorylation, and apoptosis in post-mitotic neurons. J Neurosci 2013; 33: 14645-14659.
  11. Jovicic A, Moser R, Santos MDFS, Silva Santos Mde F, Luthi-Carter R. MicroRNA-22 overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington's Disease-related mechanisms. Plos One 2013; 8: 54222.
  12. Gunn-Moore D, Kaidanovich-Beilin O, Gallego-Iradi MC, Gunn-Moore F, Lovestone S. Alzheimer's disease in humans and other animals: A consequence of post-reproductive life span and longevity rather than aging. Alzheimers Dement 2018; 14: 195-204.
  13. Segerstrom SC. Personality and incident Alzheimer's disease: Theory, evidence, and future directions. J Gerontol 2018; 12: 43.
  14. Lu J, Shu R, Zhu Y. Dysregulation and dislocation of SFPQ disturbed DNA organization in Alzheimer's Disease and Frontotemporal Dementia. J Alzheimers Dis 2018; 22: 1311-1321.
  15. Mnn V, Ras LF, DeFelice FG. Connecting Alzheimer's disease to diabetes: Underlying mechanisms and potential therapeutic targets. Basic Clin Med 2018; 136: 160-171.
  16. An Y, Varma VR, Varma S, Casanova R, Dammer E, Pletnikova O. Evidence for brain glucose dysregulation in Alzheimer's disease. Alzheimers Dement 2018; 14: 318-329.
  17. Kay DW. Genetics, Alzheimer's disease and senile dementia. British J Psychiatr 2018; 154: 311-320.
  18. Hu X, Song C, Fang M, Li C. Simvastatin inhibits the apoptosis of hippocampal cells in a mouse model of Alzheimer's disease. Exp Ther Med 2018; 15: 1795-1802.
  19. Gu C, Chen C, Wu R, Dong T, Hu X, Yao Y, et al. Long noncoding RNA EBF3-AS promotes neuron apoptosis in Alzheimer's Disease. DNA Cell Biol 2018; 37: 220-226.
  20. Zhang Y, Wang J, Wang C, Li Z, Liu X, Zhang J, et al. Pharmacological basis for the use of Evodiamine in Alzheimer's Disease: Anti-oxidation and anti-apoptosis. Int J Mol Sci 2018; 19: 5.
  21. Ting Y, Medina DJ, Strair RK, Schaar DG. Differentiation-associated miR-22 represses Max expression and inhibits cell cycle progression. Biochem Biophys Res Commun 2010; 394: 606-611.
  22. Xu D, Takeshita F, Hino Y, Fukunaga S, Kudo Y, Tamaki A, et al. MiR-22 represses cancer progression by inducing cellular senescence. J Cell Biol 2011; 193: 409-424.
  23. Song SJ, Ito K, Ala U, Kats L, Webster K, Sun SM, et al. The oncogenic microRNA (miR-22) targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell 2013; 13: 87-101.
  24. Huang S, Wang S, Bian C, Yang Z, Zhou H, Zeng Y, et al. Upregulation of miR-22 promotes osteogenic differentiation and inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by repressing HDAC6 protein expression. Stem Cells Dev 2012; 21: 2531-2540.
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