Permeability of the blood-brain barrier in toxic parkinsonism
- Authors: Gradinar М.М.1, Chernykh I.V.1, Abalenikhina Y.V.1, Shchulkin А.V.1, Yakusheva Е.N.1
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Affiliations:
- Ryazan State Medical University named after Academician I.P. Pavlov
- Issue: Vol 27, No 10 (2024)
- Pages: 32-37
- Section: Problems of experimental biology and medicine
- URL: https://bakhtiniada.ru/1560-9596/article/view/270958
- DOI: https://doi.org/10.29296/25877313-2024-10-05
- ID: 270958
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Abstract
Introduction. Parkinson's disease (PD) is a chronic neurodegenerative disease of the central nervous system with accumulation of alpha-synuclein and degeneration of nigrostriatal neurons. A number of studies have shown that one of the links in the pathogenesis of PD may also be microdamage of blood vessels. However, how these changes affect intercellular contacts of endothelial cells and the permeability of the blood-brain barrier has not yet been studied.
The aim of the study. To study the permeability of the blood-brain barrier and the level of proteins of intercellular contacts in experimental toxic parkinsonism.
Material and methods. The study was performed on male Wistar rats weighing 280-320 g. Toxic parkinsonism was modeled by subcutaneous administration of rotenone at a dose of 2.5 mg/kg 1 time per day for 7 and 28 days. Dopamine levels were determined in the striatum and midbrain by the ELISA method, and the level of intercellular contact proteins occludin, E-cadherin and ZO-1 were analyzed in the cerebral cortex by the western blot. The permeability of the blood-brain barrier was assessed by penetration of Evans blue dye into brain tissue.
Results. The administration of rotenone caused the development of experimental parkinsonism, which manifested itself in a typical clinical picture and a decrease in dopamine levels in the striatum and midbrain on days 7 and 28 of administration. At the same time, there was a decrease in the relative amounts of occludin, E-cadherin and ZO-1. These biochemical changes led to the permeability of the blood-brain barrier to the Evans blue dye on the 7th and 28th days of the experiment, which indicates an increase in the permeability of the blood-brain barrier.
Conclusion. Thus, in rotenone-induced parkinsonism, the permeability of the blood-brain barrier increases, which is caused by a decrease in specific tight junction proteins that form the connection between endothelial cells and the perivascular microenvironment. The results obtained make a significant contribution to modern understanding of the pathogenesis of Parkinson's disease and allow to identify new approaches to its treatment.
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##article.viewOnOriginalSite##About the authors
М. М. Gradinar
Ryazan State Medical University named after Academician I.P. Pavlov
Author for correspondence.
Email: masha.gradinar1995@mail.ru
ORCID iD: 0000-0002-2246-4127
Assistant, Department of Pharmacology
Russian Federation, 9 Vysokovoltnaya str., Ryazan, 390026I. V. Chernykh
Ryazan State Medical University named after Academician I.P. Pavlov
Email: ivchernykh88@mail.ru
ORCID iD: 0000-0002-5618-7607
Dr.Sc. (Biol.), Associate Professor, Head of the Department of Pharmaceutical Chemistry and Pharmacognosy
Russian Federation, 9 Vysokovoltnaya str., Ryazan, 390026Yu. V. Abalenikhina
Ryazan State Medical University named after Academician I.P. Pavlov
Email: abalenihina88@mail.ru
ORCID iD: 0000-0003-0427-0967
Dr.Sc. (Med.), Associate Professor, Department of Biological Chemistry
Russian Federation, 9 Vysokovoltnaya str., Ryazan, 390026А. V. Shchulkin
Ryazan State Medical University named after Academician I.P. Pavlov
Email: alekseyshulkin@rambler.ru
ORCID iD: 0000-0003-1688-0017
Dr.Sc. (Med.), Associate Professor, Department of Pharmacology
Russian Federation, 9 Vysokovoltnaya str., Ryazan, 390026Е. N. Yakusheva
Ryazan State Medical University named after Academician I.P. Pavlov
Email: e.yakusheva@rzgmu.ru
ORCID iD: 0000-0001-6887-4888
Dr.Sc. (Med.), Professor, Head of the Department of Pharmacology
Russian Federation, 9 Vysokovoltnaya str., Ryazan, 390026References
- Akhmetzhanov V.K., Shashkin Ch.S., Kerimbayev T.T. Parkinson's disease. Diagnostic criteria. Differential diagnosis. Journal Neurosurgery and Neurology of Kazakhstan. 2016; 4(45): 18–25. (In Russ.) URL: https://cyberleninka.ru/article/n/bolezn-parkinsona-kriterii-diagnostiki-differentsialnaya-diagnostika
- van der Mark M., Brouwer M., Kromhout H., Nijssen P. et al. Is pesticide use related to Parkinson disease? Some clues to heterogeneity in study results. Environ Health Perspect. 2012; 120(3): 340–347. doi: 10.1289/ehp.1103881.
- Sherer T.B., Richardson J.R., Testa C.M. et al. Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease. J Neurochem. 2007; 100(6): 1469–1479. doi: 10.1111/j.1471-4159.2006.04333.x.
- Agency Toxic Subst. Dis. Registry (ATSDR). Toxicological profile for toxaphene. US Dep. Health Hum. Serv., Atlanta, Ga. 2010. http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=548&tid=99.
- Pan-Montojo F., Schwarz M., Winkler C. et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep. 2012;2:898. doi: 10.1038/srep00898.
- Tanner C.M., Kamel F., Ross G.W. et al. Rotenone, paraquat, and Parkinson's disease. Environ Health Perspect. 2011; 119(6): 866–872. doi: 10.1289/ehp.1002839.
- Desai B.S., Monahan A.J., Carvey P.M., Hendey B. Blood-brain barrier pathology in Alzheimer's and Parkinson's disease: implications for drug therapy. Cell Transplant. 2007; 16(3): 285–299. doi: 10.3727/000000007783464731.
- Chernykh I.V., Shchulkin A.V., Mylnikov P.Yu. et al. Functional activity of P-glycoprotein in blood-brain barrier during experimental Parkinson's syndrome. I.P. Pavlov Russian Medical Biological Herald. 2019; 27(2): 150–159 (In Russ.). doi: 10.23888/PAVLOVJ2019272150-159.
- Chernykh I.V., Shchulkin A.V., Gatsanoga M.V. et al. Functional activity of P-glycoprotein with underlying brain ischemia. Science of the young (Eruditio Juvenium). 2019; 7(1): 46–52 (In Russ.). doi: 10.23888/HMJ20197146-52.
- Voronkov D.N., Dikalova Yu.V., Khudoerkov R.M. et. al. Brain nigrostriatal system changes in rotenone-induced parkinsonism (quantitative immune-morphological study). Annals of Neurology 2013; 7(2): 34–38. (In Russ.). URL: https://cyberleninka.ru/article/n/izmeneniya-v-nigrostriatnyh obrazovaniyah-mozga-pri-modelirovanii-parkinsonizma-indutsirovannogo-rotenonom-kolichestvennoe.
- Mironov A.N. Guidelines for conducting preclinical studies of medicines. Part one. M.: Vulture and K, 2012. 944 p.12. (In Russ.).
- Jin Z., Ke J., Guo P. et al. Quercetin improves blood-brain barrier dysfunction in rats with cerebral ischemia reperfusion via Wnt signaling pathway. Am J Transl Res. 2019; 11(8): 4683–4695. Published 2019 Aug 15.
- Wang Q., Deng Y., Huang L. et al. Hypertonic saline downregulates endothelial cell-derived VEGF expression and reduces blood-brain barrier permeability induced by cerebral ischaemia via the VEGFR2/eNOS pathway. Int J Mol Med. 2019; 44(3): 1078–1090. doi: 10.3892/ijmm.2019.
- Begley D.J. ABC transporters and the blood-brain barrier. Curr Pharm Des. 2004; 10(12): 1295–1312. doi: 10.2174/1381612043384844.
- Sharif A.E., Abdurashitov A.S., Namykin A.A. et. al. Changes in Blood-Brain Barrier Permeability under the Influence of Loud Sound. Izv. Saratov Univ. (N. S.), Ser. Chemistry. Biology. Ecology. 2019; 19(3): 312−321 (In Russ.). doi: 10.18500/1816-9775-2019-19-3-312-321.
- Sweeney M.D., Zhao Z., Montagne A. et al. Blood-Brain Barrier: From Physiology to Disease and Back. Physiol Rev. 2019; 99(1): 21–78. doi: 10.1152/physrev.00050.2017.
- Tornavaca O., Chia M., Dufton N. et al. ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. J Cell Biol. 2015; 208(6): 821–838. doi: 10.1083/jcb.201404140.
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