Investigation of Parkinsonism Development Mechanisms and Novel Approaches to Multisystem Neurorehabilitation

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Abstract

Parkinsonism is one of the most prevalent neurological syndromes, characterized by the disruption of the dopaminergic system of the brain. It has been demonstrated that locomotor and postural functions are amongst the earliest to be compromised. The mechanisms underlying parkinsonism remain largely unexplored, necessitating the development of novel etiopathogenetic treatment approaches. Transgenic knockout (KO) animals serve as a unique model for studying the molecular and genetic basis of brain functioning in both normal and pathological conditions. This review focuses on certain transgenic animal models used to investigate disruptions in the extrapyramidal nigrostriatal control of spinal and brainstem sensorimotor networks. Rats with a dopamine transporter deficiency (DAT-KO) are widely utilized to study the dopaminergic system. The administration of alpha-methyl-p-tyrosine (AMPT), a dopamine synthesis inhibitor, to these animals allows for the creation of a unique reversible parkinsonism model. The TAAR-KO mice model provides a valuable tool for evaluating the functional significance of the trace amine (TA) system and its associated receptors (trace amine associated receptors, TAAR) in sensorimotor control. Early studies have demonstrated the influence of TAAR1 and TAAR5 receptors on dopamine levels and the state of dopaminergic neurons. Notably, TAAR-KO animals exhibit improved motor abilities and coordination skills compared to wild-type animals. Based on these findings, it can be hypothesized that targeting trace amine receptors may help restore the function of dopaminergic neurons and compensate for motor disturbances associated with parkinsonism. Electrical stimulation of the spinal cord is capable of activating neuronal networks, enhancing synaptic plasticity, and promoting functional recovery when dopaminergic neurotransmission is impaired. In combination with the effects on trace amine receptors, this approach, as part of the previously proposed multisystem neurorehabilitation strategy, may contribute to a synergistic therapeutic effect.

About the authors

Y. I. Sysoev

Pavlov Institute of Physiology

Email: susoyev92@mail.ru
St. Petersburg, Russia

D. S. Kalinina

Institute of Translational Biomedicine, St. Petersburg State University; Neurobiology Program, Scientific Center for Genetics and Life Sciences, Scientific and Technological University “Sirius”

St. Petersburg, Russia; Federal Territory Sirius, Russia

A. E. Makhortykh

Neurobiology Program, Scientific Center for Genetics and Life Sciences, Scientific and Technological University “Sirius”

Federal Territory Sirius, Russia

P. E. Musienko

Institute of Translational Biomedicine, St. Petersburg State University; Neurobiology Program, Scientific Center for Genetics and Life Sciences, Scientific and Technological University “Sirius”; Federal center of brain research and neurotechnologies

Email: pol-spb@mail.ru
St. Petersburg, Russia; Federal Territory Sirius, Russia; Moscow, Russia

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