Pharmacocorrection of mitochondrial dysfunction and energy imbalance of substantia nigra neurons in experimental Parkinson's disease in rats

Volodymyr Maramukha

DOI: http://dx.doi.org/10.12775/JEHS.2020.10.11.013

Abstract


Parkinson's disease (PD) is a progressive disease and the incidence increases markedly with age, treatment has significantly improved the quality of life of patients with PD, but statistics show that these patients continue to show shorter life expectancies compared to the general population.

Aim of the study. To investigate the features of changes in energy balance and mitochondrial dysfunction on the basis of experimental studies in rats in the modeling of PD and justify the development of possible treatment regimens with specific neuroprotective effects on the dopaminergic system.

Materials and methods. The study was carried out on 90 Wistar rats at the age of 6 months weighing 220-290 grams. Parkinsonism was induced by the administration of the neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to experimental rats with neuroprotective treatment: I – Intact (passive control); II – animals with experimental Parkinson's disease (PD, active control); III – PD + Amantadine (AM) IV – PD + AM + Cerebrocurin; V – PD + AM + Pramistar; VI – PD + AM + Gliatilin; VII – PD + AM + Noofen; VIII – PD + AM + Pronoran; IX – PD + AM + Melatonin.

Results. Under conditions of formation of experimental PD in rats develops energy deficiency of neuronal cells and dysfunction of the Krebs cycle with a predominance of anaerobic oxidation of the substrate, as well as the development of mitochondrial dysfunction. Prescribed neuroprotective drugs significantly improved energy metabolism in the brain of rats with PD within statistical significance, increased levels of ATP and ADP, enzymatic activity of mCPK and ATPase, decreased levels of AMP, especially pronounced drugs melatonin, cerebrocurin, gliatilin and pronoran. Neuroprotective therapy of experimental PD in rats contributed to a statistically significant increase in the values of pyruvate, malate, LDH and MDG, and also led to a decrease in the values of lactate and lactic acidosis in brain tissues. The appointment of neuroprotective therapy with basic amantadine therapy led to an increase in energy charge, energy potential, phosphorylation index and thermodynamic control of respiration in the mitochondria of neurons, especially in the groups of melatonin, cerebrocurin, gliatilin and pronoran.

Conclusions. Pharmacocorrection of mitochondrial dysfunction and energy imbalance of dopaminergic neurons in experimental PD in rats may indirectly or directly inhibite to the progression of pathology in PD.


Keywords


Parkinson's disease; neuroprotection; mitochondrial dysfunction; energy balance; melatonin

Full Text:

PDF

References


Sveinbjornsdottir S. The clinical symptoms of Parkinson's disease. J Neurochem. 2016 Oct;139 Suppl 1:318-324. doi: 10.1111/jnc.13691. Epub 2016 Jul 11. PMID: 27401947.

Opara J, Małecki A, Małecka E, Socha T. Motor assessment in Parkinson`s disease. Ann Agric Environ Med. 2017 Sep 21;24(3):411-415. doi: 10.5604/12321966.1232774. Epub 2017 May 11. PMID: 28954481.

Lotankar S, Prabhavalkar KS, Bhatt LK. Biomarkers for Parkinson's Disease: Recent Advancement. Neurosci Bull. 2017 Oct;33(5):585-597. doi: 10.1007/s12264-017-0183-5. Epub 2017 Sep 21. PMID: 28936761; PMCID: PMC5636742.

Cabreira V, Massano J. Doença de Parkinson: Revisão Clínica e Atualização [Parkinson's Disease: Clinical Review and Update]. Acta Med Port. 2019 Oct 1;32(10):661-670. Portuguese. doi: 10.20344/amp.11978. PMID: 31625879.

Cacabelos R. Parkinson's Disease: From Pathogenesis to Pharmacogenomics. Int J Mol Sci. 2017 Mar 4;18(3):551. doi: 10.3390/ijms18030551. PMID: 28273839; PMCID: PMC5372567.

Falkenburger BH, Saridaki T, Dinter E. Cellular models for Parkinson's disease. J Neurochem. 2016 Oct;139 Suppl 1:121-130. doi: 10.1111/jnc.13618. Epub 2016 Apr 18. PMID: 27091001.

Bose A, Beal MF. Mitochondrial dysfunction in Parkinson's disease. J Neurochem. 2016 Oct;139 Suppl 1:216-231. doi: 10.1111/jnc.13731. Epub 2016 Aug 21. PMID: 27546335.

Nguyen M, Wong YC, Ysselstein D, Severino A, Krainc D. Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson's Disease. Trends Neurosci. 2019 Feb;42(2):140-149. doi: 10.1016/j.tins.2018.11.001. Epub 2018 Nov 30. PMID: 30509690; PMCID: PMC6452863.

Rocha EM, De Miranda B, Sanders LH. Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease. Neurobiol Dis. 2018 Jan;109(Pt B):249-257. doi: 10.1016/j.nbd.2017.04.004. Epub 2017 Apr 8. PMID: 28400134.

Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, Santos DP, Blanz J, Obermaier CD, Strojny C, Savas JN, Kiskinis E, Zhuang X, Krüger R, Surmeier DJ, Krainc D. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. Science. 2017 Sep 22;357(6357):1255-1261. doi: 10.1126/science.aam9080. Epub 2017 Sep 7. PMID: 28882997; PMCID: PMC6021018.

Subramaniam SR, Chesselet MF. Mitochondrial dysfunction and oxidative stress in Parkinson's disease. Prog Neurobiol. 2013 Jul-Aug;106-107:17-32. doi: 10.1016/j.pneurobio.2013.04.004. Epub 2013 Apr 30. PMID: 23643800; PMCID: PMC3742021.

Li H, Ham A, Ma TC, Kuo SH, Kanter E, Kim D, Ko HS, Quan Y, Sardi SP, Li A, Arancio O, Kang UJ, Sulzer D, Tang G. Mitochondrial dysfunction and mitophagy defect triggered by heterozygous GBA mutations. Autophagy. 2019 Jan;15(1):113-130. doi: 10.1080/15548627.2018.1509818. Epub 2018 Oct 12. PMID: 30160596; PMCID: PMC6287702.

Larsen SB, Hanss Z, Krüger R. The genetic architecture of mitochondrial dysfunction in Parkinson's disease. Cell Tissue Res. 2018 Jul;373(1):21-37. doi: 10.1007/s00441-017-2768-8. Epub 2018 Jan 25. PMID: 29372317; PMCID: PMC6015629.

Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE. Parkinson disease. Nat Rev Dis Primers. 2017 Mar 23;3:17013. doi: 10.1038/nrdp.2017.13. PMID: 28332488.

Park JS, Davis RL, Sue CM. Mitochondrial Dysfunction in Parkinson's Disease: New Mechanistic Insights and Therapeutic Perspectives. Curr Neurol Neurosci Rep. 2018 Apr 3;18(5):21. doi: 10.1007/s11910-018-0829-3. PMID: 29616350; PMCID: PMC5882770.

Macdonald R, Barnes K, Hastings C, Mortiboys H. Mitochondrial abnormalities in Parkinson's disease and Alzheimer's disease: can mitochondria be targeted therapeutically? Biochem Soc Trans. 2018 Aug 20;46(4):891-909. doi: 10.1042/BST20170501. Epub 2018 Jul 19. PMID: 30026371.

Ryan BJ, Hoek S, Fon EA, Wade-Martins R. Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem Sci. 2015 Apr;40(4):200-10. doi: 10.1016/j.tibs.2015.02.003. Epub 2015 Mar 8. PMID: 25757399.

Raza C, Anjum R, Shakeel NUA. Parkinson's disease: Mechanisms, translational models and management strategies. Life Sci. 2019 Jun 1;226:77-90. doi: 10.1016/j.lfs.2019.03.057. Epub 2019 Apr 10. PMID: 30980848.

Pozo Devoto VM, Falzone TL. Mitochondrial dynamics in Parkinson's disease: a role for α-synuclein? Dis Model Mech. 2017 Sep 1;10(9):1075-1087. doi: 10.1242/dmm.026294. PMID: 28883016; PMCID: PMC5611962.


Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM




Journal of Education, Health and Sport formerly Journal of Health Sciences

Declaration on the original version.

Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

Archives 2011 - 2014

PBN 2011 - 2014

https://pbn.nauka.gov.pl/sedno-webapp/search?search&searchCategory=WORK&filter.inJournal=36616

POL-index 2011 - 2014

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-32a319c5-a850-4f44-ba70-1418a6087655

BASE 2011 - 2014

https://www.base-search.net/Search/Results?lookfor=Journal+of+Health+Sciences+%28Radom%29&type=all&oaboost=1&ling=1&name=&thes=&refid=dcrespl&newsearch=1

http://elibrary.ru/contents.asp?titleid=37467

http://journal.rsw.edu.pl/index.php/JHS/issue/archive

Indexed in Bases, Bazy indeksacyjne: ERIH Plus, Worldcat, PBN/POL-Index, ICI Journals Master List, Directory of Open Access Journals (DOAJ), ZBD, Ulrich's periodicals, Google Scholar, Polska Bibliografia Lekarska, EuroPub database, NLM Catalog Result - NCBI, BASE, Russian Sciences Index, Arianta.

https://zdb-katalog.de/title.xhtml?idn=1080187162

https://europub.co.uk/journals/22625

US NLM = 101679844

101679844 - NLM Catalog Result - NCBI

https://www.ncbi.nlm.nih.gov/nlmcatalog/101679844

Find a library that holds this journal: http://worldcat.org/issn/23918306

 

PBN Poland

https://pbn.nauka.gov.pl/sedno-webapp/journals/49068

POL-index

https://pbn.nauka.gov.pl/polindex-webapp/browse/journal/journal-c39c8169-88d2-45db-9e7f-d948ce9981c4

BASE

https://www.base-search.net/Search/Results?join=AND&bool0[]=AND&lookfor0[]=2391-8306&type0[]=all&page=11&l=pl&oaboost=1&refid=dcpagepl

Redaction, Publisher and Editorial Office

Publisher and Editorial Office
Department of Physical Culture,
Faculty of Earth Sciences and Spatial Management,
Nicolaus Copernicus University in Toruń, Poland
Address: Str. Lwowska 1, 87-100 Toruń, Poland

  Open Access ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

The journal has been approved for inclusion in ERIH PLUS.

The ERIH PLUS listing of the journal is available at https://dbh.nsd.uib.no/publiseringskanaler/erihplus/periodical/info?id=485984

Indexed in Index Copernicus Journals Master List.

http://journals.indexcopernicus.com/Journal+of+Education+Health+and+Sport,p24782242,3.html

ICV 2019 = 100.00 ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

RG Journal Impact: 0.18 *

*This value is calculated using ResearchGate data and is based on average citation counts from work published in this journal. The data used in the calculation may not be exhaustive.

RG Journal impact history

2020Available summer 2021
2018 / 20190.18
20170.07
20160.03

RG Journal impact over time

RG Journal impact
0.180.160.140.120.100.080.060.040.02201620172018
  

Indexed in Polish Scholarly Bibliography (PBN) (PBN Polska Bibliografia Naukowa) (https://pbn.nauka.gov.pl/journals/36616)

is a portal of the Polish Ministry of Science and Higher Education, collecting information on publications of Polish scientists and on Polish and foreign scholarly journals. Polish Scholarly Bibliograhpy is a part of POL-on - System of Information on Higher Education. It is operated by the Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw.

Indexed in Russian Sciences Index Российский индекс научного цитирования (РИНЦ) http://elibrary.ru/contents.asp?titleid=37467

Indexed in Arianta Polish scientific and professional electronic journals Aneta Drabek i Arkadiusz Pulikowski

(http://www1.bg.us.edu.pl/bazy/czasopisma/czasop_full.asp?id=3595)

Partnerzy platformy czasopism