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Abstract <p>Parkinsonism is one of the most common neurological syndromes,characterized by the dysfunction of the dopaminergic system in thebrain, with locomotor and postural functions being compromised among thefirst. The mechanisms underlying parkinsonism development remainlargely unexplored. It is necessary to search for novel etiopathogenetictreatment approaches. Transgenic knockout (KO) animals serve asunique model systems for studying the molecular and genetic basisof brain function in normal and pathological conditions. This reviewfocuses on several transgenic animal models used to investigatedisorders of extrapyramidal nigrostriatal control over spinal andbrainstem sensorimotor networks. Dopamine transporter knockout (DAT-KO)rats are widely employed in dopaminergic system research, as theadministration of alpha-methyl-p-tyrosine (AMPT), a dopamine synthesisblocker, to these animals creates a unique experimental model ofreversible parkinsonism. Early studies have demonstrated the influenceof trace amines (TA) and trace amine-associated receptors (TAARs), specificallyTAAR1 and TAAR5, on dopamine levels and the state of dopaminergicneurons. Notably, TAAR knockout (TAAR-KO) animals exhibited improvedmotor abilities and coordination skills compared to the wild-type.Based on these findings, it can be hypothesized that targeting TAARsin parkinsonism symptoms may restore the function of dopaminergicneurons and compensate for motor impairments. Electrical stimulationof the spinal cord is able to activate neural networks, enhance synapticplasticity, and promote functional recovery in cases of disrupteddopaminergic neurotransmission. Combined with TAAR modulation, thisapproach, as part of the previously proposed multisystem neurorehabilitationstrategy, may ensure a synergistic therapeutic effect.</p>

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Mechanisms of Parkinsonism Development and Novel Approaches to Multisystem Neurorehabilitation

  • 期刊论文

  • 发表日期：

    2025年5月1日

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  • Y. I. Sysoev,
  • D. S. Kalinina,
  • A. E. Makhortykh,
  • P. E. Musienko

摘要

Abstract

Parkinsonism is one of the most common neurological syndromes,characterized by the dysfunction of the dopaminergic system in thebrain, with locomotor and postural functions being compromised among thefirst. The mechanisms underlying parkinsonism development remainlargely unexplored. It is necessary to search for novel etiopathogenetictreatment approaches. Transgenic knockout (KO) animals serve asunique model systems for studying the molecular and genetic basisof brain function in normal and pathological conditions. This reviewfocuses on several transgenic animal models used to investigatedisorders of extrapyramidal nigrostriatal control over spinal andbrainstem sensorimotor networks. Dopamine transporter knockout (DAT-KO)rats are widely employed in dopaminergic system research, as theadministration of alpha-methyl-p-tyrosine (AMPT), a dopamine synthesisblocker, to these animals creates a unique experimental model ofreversible parkinsonism. Early studies have demonstrated the influenceof trace amines (TA) and trace amine-associated receptors (TAARs), specificallyTAAR1 and TAAR5, on dopamine levels and the state of dopaminergicneurons. Notably, TAAR knockout (TAAR-KO) animals exhibited improvedmotor abilities and coordination skills compared to the wild-type.Based on these findings, it can be hypothesized that targeting TAARsin parkinsonism symptoms may restore the function of dopaminergicneurons and compensate for motor impairments. Electrical stimulationof the spinal cord is able to activate neural networks, enhance synapticplasticity, and promote functional recovery in cases of disrupteddopaminergic neurotransmission. Combined with TAAR modulation, thisapproach, as part of the previously proposed multisystem neurorehabilitationstrategy, may ensure a synergistic therapeutic effect.