FORMATION OF ULTRASTRUCTURAL ADAPTIVE REACTIONS IN BODY TISSUES UNDER EXPERIMENTAL PARKINSONISM
Y.V. Putiy1, O.L. Fuchko2, N.M. Vashchenko1, K.V. Rozova1
- Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
- Uzhhorod National University, Ukraine
DOI: https://doi.org/10.15407/fz69.03.074
![](/images/cite.png)
Abstract
We studied changes in the ultrastructure of brain tissues -
medulla oblongata and striatum, as well as lung and heart
tissues in experimental parkinsonism caused by the action of
rotenone, which was administered once or for 2 weeks. It has
been shown that during the development of a Parkinson-like
state the ultrastructure of tissues disturbance, the development
of mitochondrial and endothelial dysfunction is observed not
only in parts of the brain, but also in other tissues of the body.
Mitochondrial dysfunction is significantly expressed in the
medulla oblongata, as evidenced by, firstly, a decrease in
the total number of mitochondria by 35.7%, and secondly,
damage to their ultrastructure in more than 40% of organelles.
Endothelial dysfunction was indicated by hyperhydration
of the blood-brain barrier. In the tissue of the striatum, the
indicated changes were insignificant, instead, a compensatory
restoration of dynamic processes in the mitochondrial
apparatus, in particular fission-fusion processes, was observed.
In the myocardium, there were also significant changes in
the ultrastructure, this indicated the development of both
mitochondrial and endothelial dysfunctions. As well as in
the medulla oblongata tissue, about 40% of mitochondria
were found to be damaged, although it should be noted
that although not pronounced, but still reliable (by 12.6%)
activation of mitochondrial morphogenesis was observed. The
histohematal barrier, in particular its endothelial layer, thinned
due to destructive processes. Violations of the ultrastructure
were also observed in the lung tissue. Significant changes in
the mitochondrial apparatus with damage to the mitochondrial
structure were revealed. However, the percentage of
structurally damaged organelles was significantly (almost 2
times) lower than in the myocardium (reached only 25%). The
thickness of the endothelial layer of the air barrier increased
by an average of 30%. In tissues where mitochondrial and
endothelial dysfunction were less pronounced during longterm administration of rotenone, adaptive changes begin
to form, which are probably also observed in people with
Parkinson’s disease, which enables them to adapt to the
existing disease.
Keywords:
experimental parkinsonism; rotenone; medulla oblongata; striatum; myocardium; lung tissue; endothelial dysfunction; mitochondrial dysfunction.
References
- Titova N, Schapira AHV, Chaudhuri KR. Nonmotor symptoms in experimental models of Parkinson's disease. In: Nonmotor Parkinson's: The Hidden Face. International Review of Neurobiology. Chaudhuri KR, Titova N. (eds). Vol. 133, Chapter 3, Elsevier, Academic Press (OX). 2017. 63-89.
CrossRef
PubMed
- Titova N, Padmakumar C, Lewis S. Parkinson's: a syndrome rather than a disease? J Neural Transm. 2017;124 (9):907-14.
CrossRef
PubMed PubMedCentral
- Mukherjee A, Cuanalo-Contreras K, Sood A, Soto C. Development of a novel pharmacophore model to screen specific inhibitors for the serine-threonine protein phosphatase calcineurin. Biochem Biophys Reports, 2022; 31(4): 101311.
CrossRef
PubMed PubMedCentral
- Paddock C. Scientists confirm the role of 'molecular switch' in Parkinson's disease. Med News Today. (9). [Internet]. 2018. Available on: https://www. medicalnewstoday.com/articles/323634.
- Burbulla LF, Song F, Mazzulli JR, Zampese E, Wong YC,Jeon S. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. Science. 2017;57(6357):1255-61.
CrossRef
PubMed PubMedCentral
- Gao J, Wang L, Liu J, Xie F, Su B, Wang X. Abnormalities of mitochondrial dynamics in neurodegenerative diseases. Antioxidants (Basel). 2017;6(2):25.
CrossRef
PubMed PubMedCentral
- Norat P, Soldozy S, Sokolowski JD, Grick CM, et al. Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation. npj Regen Med; 2020; 5(22):1-09.
CrossRef
PubMed PubMedCentral
- Savica R, Grossardt BR, Bower JH, Ahlskog JE, Boeve BF, Graff-Radford J. Survival and causes of death among people with clinically diagnosed synucleinopathies with Parkinsonism: A population-based study. JAMA Neurol. 2017;74(7):839-46.
CrossRef
PubMed PubMedCentral
- Mielcarek M, Inuabasi L, Bondulich MK, Muller T, Osborne GF, Franklin SA. Dysfunction of the CNS-heart axis in mouse models of Huntington's disease. PLoS Genet. 2014; 10 (8): e1004550.
CrossRef
PubMed PubMedCentral
- von Wrangel C, Schwabe K, John N, Krauss JK, Alam M. The rotenone-induced rat model of Parkinson's disease: Behavioral and electrophysiological findings. Behav Brain Res. 2015; 279 (15) 52-61.
CrossRef
PubMed
- Patten DA, Wong J, Khacho M, Soubannier V, Mailloux R, Pilon-Larose K. OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand. EMBO J. 2014; 33(22): 2676-91.
CrossRef
PubMed PubMedCentral
- Simon DK, Tanner CM, Brundin P. Parkinson disease epidemiology, pathology, genetics and pathophysiology. Clin Geriatr Med. 2020; 36 (1):1-12.
CrossRef
PubMed PubMedCentral
- Weakley BS. A Beginner's Handbook in Electron Microscopy. Edinburg and London: Churchill Livingstone. 1972.
- Weibel ER. Stereological principles for morphometry in electron microscopic cytology. Int Rev Cytol. 1969, 26 (2): 235-302.
CrossRef
PubMed
- Constable PD, Hinchcliff KW, Done SH, Grünberg W. Diseases of the nervous system veterinary medicine. Vet Med. 2017, (14):1155-370.
- Sarbishegi M, Charkhat Gorgich E A. The effects of celecoxib on rotenone-induced rat model of Parkinson's disease: Suppression of neuroinflammation and oxidative stress-mediated apoptosis. Gene Cell Tissue, 2019; 6 (2): e92178.
CrossRef
- Zhu LH, Luo XG, Zhou YS. Lack of association between three single nucleotide polymorphisms in the PARK9, PARK15, and BST1 genes and Parkinson's disease in the northern Han Chinese population. Chin Med J (Engl). 2012;125(4): 588-92.
CrossRef
- Javadov S, Chapa-Dubocq X, Makarov V. Different approaches to modeling analysis of mitochondrial swelling. Mitochondrion. 2018; 38 (1):58-70.
CrossRef
PubMed PubMedCentral
- Lin A, Peiris NJ, Dhaliwal H, Hakim M, Li W, Ganesh S, Ramaswamy Y, Patel S, Misra A. Mural cells: Potential therapeutic targets to bridge cardiovascular disease and neurodegeneration. Cells. 2021;10 (3):593.
CrossRef
PubMed PubMedCentral
- Lang M, Grünewald A, Pramstaller PP, Hicks AA, Pichler I. A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson's disease by highlighting the use of cybrid models. Cell Mol Life Sci. 2022;79(283).
CrossRef
PubMed PubMedCentral
- Chen W, Guo L, Li M, Wei C, Li S, Xu R. The pathogenesis of amyotrophic lateral sclerosis: Mitochondrial dysfunction, protein misfolding and epigenetics. Brain Res. 2022; 786 (1):147904.
CrossRef
PubMed
- Campello S, Scorrano L. Mitochondrial shape changes: orchestrating cell pathophysiology. EMBO Rep. 2010;11(9):678-84.
CrossRef
PubMed PubMedCentral
- Cogliati S, Frezza C, Soriano ME, Varanita T, QuintanaCabrera R, Corrado M. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell. 2013;155(1):160-71.
CrossRef
PubMed PubMedCentral
|