IS THERE AN ORGAN-SPECIFIC EXPRESSION OF CANDIDATE GENES (DJ1, PINK1) IN TISSUES OF THE ORGANISM UNDER EXPERIMENTAL PARKINSONISM AND ITS PATHOGENETIC THERAPY?

Rozova Kateryna Vsevolodovna Rozova Kateryna Vsevolodovna,Putiy Yuliya Vladimirovna Putiy Yuliya Vladimirovna

doi:10.31435/rsglobal_sr/30012021/7378

Rozova Kateryna Vsevolodovna Rozova Kateryna Vsevolodovna, Putiy Yuliya Vladimirovna Putiy Yuliya Vladimirovna

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https://doi.org/10.31435/rsglobal_sr/30012021/7378

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Abstract

It have been studied the changes in the structural and functional state of mitochondria and expression of PINK1 and DJ1 genes in brain tissue - medulla oblongata and striatum and lung and heart tissue in experimental parkinsonism and its pathogenetic treatment with the help of a broad-spectrum antihypoxant Kapikor. It was shown that undrt experimental parkinsonism, in addition to damage to the ultrastructure of the mitochondrial apparatus in cells of body tissues, there are significant changes in mRNA expression of DJ1 and PINK1 genes, which are associated with the formation of mitochondrial dysfunction. They have a multidirectional character in the tissues of the brain - decrease, and in the tissues of the heart and lungs - increase. The degree of such changes in expression is organ-specific and more pronounced in the tissues of the visceral organs than in the tissues of the brain. Also, it was shown that the use of broad-spectrum antioxidant, which contains mildenium dehydrate and gamma-butyrobetaine dihydrate, there are significant changes in the expression of mRNA genes DJ1 and PINK1, which are also organ-specific - the expression of mRNA of all DJ1 genes increased in to a greater extent, the expression of PINK1 gene mRNA decreased sharply in brain tissues, and also increased sharply in lung and heart tissues. The data obtained indicate a complex and ambiguous relationship between the level of expression of the studied candidate genes involved in the formation of experimental parkinsonism, and the severity of mitochondrial dysfunction, which is one of the pathogenetic causes of parkinsonism.

Highlights

In the 21st century, Parkinson's disease (PD) has become the second most common neurodegenerative disease in the world after Alzheimer's disease
Studies have shown that changes in the level of mRNA expression of the DJ1 gene in experimental parkinsonism (EP) was unidirectional in all studied tissues, namely its reduction: in the medulla oblongata - by 11.4%; in the striatum - by 19.2%; in heart tissue - 11.7 times, and in lung tissue - by 3 orders of magnitude, ie almost to zero (Fig. 1)
Regarding the level of mRNA expression of the PINK1 gene, the dynamics of changes was unidirectional in all tissues, but inverse to that established with respect to the DJ1 gene (Fig. 2)

Summary

Introduction

In the 21st century, Parkinson's disease (PD) has become the second most common neurodegenerative disease in the world after Alzheimer's disease. The results of experimental and clinical studies indicate that in the pathogenesis of this disease, as well as a significant part of other emerging pathological conditions, mitochondrial (MD) and / or endothelial dysfunction (ED). The study of the genetic nature of the disease began in the late twentieth century after the identification of mutations in the gene encoding the protein α-synuclein (SNCA), identifying the role of this protein in the formation of Lewy bodies and, its participation in the development of PD. Of the many candidate genes studied, Parkin, PINK1, and DJ1 are often considered [2]. Parkin cooperates with PINK1 in the so-called quality control, such as neurons, by activating mitophagy in conditions of mitochondrial damage [3]

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