The use of neurotoxins in fundamental, medical and biological sciences on the example of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Abstract

Introduction. Neurotoxins are a class of chemicals that damage neurons. Some pesticides have a similar effect. The increase in areas with developed heavy industry and agriculture, uncontrolled use of pesticides contribute to the emergence and progression of Alzheimer’s and Parkinson’s disease (PD). The insidiousness of PD is that it is still incurable, since there is no early diagnosis: for decades it has been asymptomatic, and by the time of manifestation there are no target neurons for therapy. Considering that the diagnosis is made at the late stages of PD development, the treatment of the disease is ineffective. It follows that in order to increase the effectiveness of treatment, it should be started as early as possible - before the appearance of motor symptoms, at the preclinical stage. To do this, it is first necessary to develop an early (preclinical) diagnosis of PD based on an in-depth study of the cellular and molecular mechanisms of pathogenesis. In order to develop early diagnosis and preventive therapy of PD, proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used in this study. Material and methods. To simulate the preclinical and clinical stages of PD, inbred lines of animals were injected with MPTP according to certain schemes. The behavior of experimental animals was assessed, and after their decapitation, the content of monoamines in the structures of the brain, peripheral organs, and blood plasma was determined by HPLC, and a morphofunctional analysis of the studied tissues and organs was performed. Results. The clinical stage of PD was modeled in animals, which corresponds to the key characteristics of PD in humans. A hypothetical preclinical stage of PD was modeled in animals, on which the method of early diagnosis was successfully tested. This model shows a number of important biochemical changes in peripheral organs, indicating the systemic nature of the disease and preceding the onset of the clinical stage of PD. Research limitations. The results of this study can only be applied to humans only after similar results have been obtained in monkeys. Limitations. Only after obtaining similar results in monkeys the results of this study can be translated to humans. Conclusion. Knowledge about the mechanisms of action of some neurotoxins is expanding, which are successfully used for the needs of fundamental, medical and biological sciences.