Changes in the reaction of mitochondrial biogenesis and mitophagy in the tissues of the cerebral cortex and hippocampus in Wistar rats under conditions of experimental Alzheimer's disease
https://doi.org/10.21626/vestnik/2024-3/10
Abstract
Objective - to evaluate changes in the processes of mitochondrial biogenesis and mitophagy in the cerebral cortex and hippocampus in Wistar rats of both genders in experimental Alzheimer's disease. Materials and methods. Alzheimer's disease was modeled in male and female Wistar rats by injection of β-amyloid aggregates 1-42 into the CA1 hippocampal part. After 30 days of exposure, the rats were decapitated, the brain was extracted, the hippocampus and cerebral cortex were isolated with further reception of the mitochondrial fraction, in which changes in the activity of succinate dehydrogenase, cytochrome c oxidase (biomarkers of mitochondrial biogenesis) and citrate synthase (biomarker of mitophagy) were evaluated by spectrophotometric method. Results. It was found that in Wistar rats of both genders under conditions of experimental Alzheimer's disease, compared to sham operated animals, there is a decrease in the activity of succinate dehydrogenase, cytochrome c oxidase and citrate synthase, both in the cerebral cortex and in the hippocampus were observed. At the same time, there were no gender differences in the activity of the studied enzymes in the hippocampus, whereas in the cerebral cortex, the activity of succinate dehydrogenase and cytochrome c oxidase in female rats was lower than in males by 23.4% (p<0.05) and 25.3% (p<0.05), respectively. Conclusion. The study showed that in Wistar rats there are gender differences in the reactions of mitochondrial biogenesis in the cerebral cortex, while in the hippocampus there are no significant differences in the reactions of mitophagy and mitochondrial biogenesis in female and male Wistar rats.
About the Authors
Dmitry I. Pozdnyakov
Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd state Medical University (PMPI - branch of VolgSMU)
Russian Federation
Russian Federation
Anastasia A. Vikhor’
Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd state Medical University (PMPI - branch of VolgSMU)
Russian Federation
Russian Federation
Student, PMPI - branch of VolgSMU, Pyatigorsk, Russian Federation
References
1. Agnello L., Ciaccio M. Neurodegenerative Diseases: From Molecular Basis to Therapy.Int J Mol Sci. 2022;23(21):12854. DOI: 10.3390/ijms232112854.
2. Scheltens P., De Strooper B., Kivipelto M., Holstege H., Chételat G., Teunissen C.E., Cummings J., van der Flier W.M. Alzheimer's disease. Lancet. 2021;397(10284):1577-1590. DOI: 10.1016/S0140-6736(20)32205-4.
3. Zhang X.X., Tian Y., Wang Z.T., Ma Y.H., Tan L., Yu J.T. The Epidemiology of Alzheimer's Disease Modifiable Risk Factors and Prevention. J Prev Alzheimers Dis. 2021;8(3):313-321. DOI: 10.14283/jpad.2021.15.
4. Wu Y., Chen M., Jiang J. Mitochondrial dysfunction in neurodegenerative diseases and drug targets via apoptotic signaling. Mitochondrion. 2019;49:35-45. DOI: 10.1016/j.mito.2019.07.003.
5. Abyadeh M., Gupta V., Chitranshi N., Gupta V., Wu Y., Saks D., Wander Wall R., Fitzhenry M.J., et al. Mitochondrial dysfunction in Alzheimer's disease - a proteomics perspective. Expert Rev Proteomics. 2021;18(4):295-304. DOI: 10.1080/14789450.2021.1918550.
6. Li P.A., Hou X., Hao S. Mitochondrial biogenesis in neurodegeneration. J Neurosci Res. 2017;95(10):2025-2029. DOI: 10.1002/jnr.24042.
7. Dong W., Wang F., Guo W., Zheng X., Chen Y., Zhang W., Shi H. Aβ25-35 Suppresses Mitochondrial Biogenesis in Primary Hippocampal Neurons. Cell Mol Neurobiol. 2016;36(1):83-91. DOI: 10.1007/s10571-015-0222-6.
8. Shefa U., Jeong N.Y., Song I.O., Chung H.J., Kim D., Jung J., Huh Y. Mitophagy links oxidative stress conditions and neurodegenerative diseases. Neural Regen Res. 2019;14(5):749-756. DOI: 10.4103/1673-5374.249218.
9. Reddy P.H., Oliver D.M. Amyloid Beta and Phosphorylated Tau-Induced Defective Autophagy and Mitophagy in Alzheimer's Disease. Cells. 2019;8(5):488. DOI: 10.3390/cells8050488.
10. Louwagie E.J., Larsen T.D., Wachal A.L., Gandy T.C.T., Eclov J.A., Rideout T.C., Kern K.A., Cain J.T., et al. Age and Sex Influence Mitochondria and Cardiac Health in Offspring Exposed to Maternal Glucolipotoxicity. iScience. 2020;23(11):101746. DOI: 10.1016/j.isci.2020.101746.
11. Demarest T.G., Waite E.L., Kristian T., Puche A.C., Waddell J., McKenna M.C., Fiskum G. Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia-ischemia. Neuroscience. 2016;335:103-113. DOI: 10.1016/j.neuroscience.2016.08.026.
12. Paxinos G., Watson J. The Rat Brain in Stereotaxic Coordinates. 7th Edition. New York: Academic Press;2013.
13. Kim H.Y., Lee D.K., Chung B.R., Kim H.V., Kim Y.Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits. J Vis Exp. 2016;(109):53308. DOI: 10.3791/53308.
14. Ju J.S., Jeon S.I., Park J.Y., Lee J.Y., Lee S.C., Cho K.J., Jeong J.M. Autophagy plays a role in skeletal muscle mitochondrial biogenesis in an endurance exercise-trained condition. J Physiol Sci. 2016 Sep;66(5): 417-430. DOI: 10.1007/s12576-016-0440-9.
15. Ding W.X., Yin X.M. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem. 2012;393(7):547-564. DOI: 10.1515/hsz-2012-0119.
16. Lennol M.P., Canelles S., Guerra-Cantera S., Argente J., García-Segura L.M., de Ceballos M.L., Chowen J.A., Frago L.M. Amyloid-β1-40 differentially stimulates proliferation, activation of oxidative stress and inflammatory responses in male and female hippocampal astrocyte cultures. Mech Ageing Dev. 2021;195:111462. DOI: 10.1016/j.mad.2021.111462.
17. Yan W., Zhang T., Kang Y., Zhang G., Ji X., Feng X., Shi G. Testosterone ameliorates age-related brain mitochondrial dysfunction. Aging (Albany NY). 2021;13(12):16229-16247. DOI: 10.18632/aging.203153.
18. Simpkins J.W., Yi K.D., Yang S.H., Dykens J.A. Mitochondrial mechanisms of estrogen neuroprotection. Biochim Biophys Acta. 2010;1800(10):1113-1120. DOI: 10.1016/j.bbagen.2009.11.013.
Review
For citations:
Pozdnyakov D.I., Vikhor’ A.A. Changes in the reaction of mitochondrial biogenesis and mitophagy in the tissues of the cerebral cortex and hippocampus in Wistar rats under conditions of experimental Alzheimer's disease. Humans and their health. 2024;27(3):92-97. (In Russ.) https://doi.org/10.21626/vestnik/2024-3/10. EDN: 616.892.32: 576.311.347
Views:
92
Email this article 