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

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.

Chronic MPTP in Mice Damage-specific Neuronal Phenotypes within Dorsal Laminae of the Spinal Cord

The neurotoxin 1-methyl, 4-phenyl, 1, 2, 3, 6-tetrahydropiridine (MPTP) is widely used to produce experimental parkinsonism. Such a disease is characterized by neuronal damage in multiple regions beyond the nigrostriatal pathway including the spinal cord. The neurotoxin MPTP damages spinal motor neurons. So far, in Parkinson’s disease (PD) patients alpha-synuclein aggregates are described in the dorsal horn of the spinal cord. Nonetheless, no experimental investigation was carried out to document whether MPTP affects the sensory compartment of the spinal cord. Thus, in the present study, we investigated whether chronic exposure to small doses of MPTP (5 mg/kg/X2, daily, for 21 days) produces any pathological effect within dorsal spinal cord. This mild neurotoxic protocol produces a damage only to nigrostriatal dopamine (DA) axon terminals with no decrease in DA nigral neurons assessed by quantitative stereology. In these experimental conditions we documented a decrease in enkephalin-, calretinin-, calbindin D28K-, and parvalbumin-positive neurons within lamina I and II and the outer lamina III. Met-Enkephalin and substance P positive fibers are reduced in laminae I and II of chronically MPTP-treated mice. In contrast, as reported in PD patients, alpha-synuclein is markedly increased within spared neurons and fibers of lamina I and II after MPTP exposure. This is the first evidence that experimental parkinsonism produces the loss of specific neurons of the dorsal spinal cord, which are likely to be involved in sensory transmission and in pain modulation providing an experimental correlate for sensory and pain alterations in PD.