Mechanisms of Parkinsonism Development and Novel Approaches to Multisystem Neurorehabilitation

Parkinsonism is one of the most common neurological syndromes, characterized by the dysfunction of the dopaminergic system in the brain, with locomotor and postural functions being compromised among the first. The mechanisms underlying parkinsonism development remain largely unexplored. It is necessary to search for novel etiopathogenetic treatment approaches. Transgenic knockout (KO) animals serve as unique model systems for studying the molecular and genetic basis of brain function in normal and pathological conditions. This review focuses on several transgenic animal models used to investigate disorders of extrapyramidal nigrostriatal control over spinal and brainstem sensorimotor networks. Dopamine transporter knockout (DAT-KO) rats are widely employed in dopaminergic system research, as the administration of alpha-methyl-p-tyrosine (AMPT), a dopamine synthesis blocker, to these animals creates a unique experimental model of reversible parkinsonism. Early studies have demonstrated the influence of trace amines (TA) and trace amine-associated receptors (TAARs), specifically TAAR1 and TAAR5, on dopamine levels and the state of dopaminergic neurons. Notably, TAAR knockout (TAAR-KO) animals exhibited improved motor abilities and coordination skills compared to the wild-type. Based on these findings, it can be hypothesized that targeting TAARs in parkinsonism symptoms may restore the function of dopaminergic neurons and compensate for motor impairments. Electrical stimulation of the spinal cord is able to activate neural networks, enhance synaptic plasticity, and promote functional recovery in cases of disrupted dopaminergic neurotransmission. Combined with TAAR modulation, this approach, as part of the previously proposed multisystem neurorehabilitation strategy, may ensure a synergistic therapeutic effect.