Rossijskij fiziologičeskij žurnal im. I.M. Sečenova

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.

Chronic pain is a complex condition that directly affects the quality of life of patients. Regulation and treatment of chronic pain are associated with a number of difficulties, primarily due to the multifactorial nature of this condition. The causes of chronic pain can be associated not only with physical damage, such as various injuries, diseases and the development of neuroinflammation, but also with a violation of the synthesis of neurotransmitters, as well as complex processes of neurogenesis. In this review, we describe the complex and multifaceted interaction between dopaminergic regulation, neurogenesis and neuroinflammation on the development of chronic pain. Further studies of these relationships can lead to the creation of targeted therapeutic strategies aimed at eliminating chronic pain. Moreover, understanding the mechanisms underlying analgesia associated with the dopamine reward system can form the basis for the development of new therapeutic approaches to relieve and control pain.

Migraine with its high prevalence, complex pathogenesis, including changes in the nervous, immune, cardiovascular systems, and limited effectiveness of drug treatment, is one of the urgent problems of modern medicine. The search for new pharmaceutical targets and development of pharmacological agents is required. Since the end of the 20th century, studies have shown the possible involvement of the brain's dopaminergic system in the pathogenesis of migraine. Migraine pain is often combined with premonitory yawning and drowsiness, accompanied by nausea and vomiting, postdromal drowsiness, euphoria and polyuria, which may be related to dopaminergic activity. The study of dopaminergic mechanisms of migraine development may form the basis of future drug lines for the therapy of cephalgia. One of the problems in modern clinical practice is the selection of therapy for the treatment and prevention of migraine. Excessive uncontrolled use of analgesics for pain attacks increases the risk of transition of episodic migraine into a chronic form. In this regard, recently great importance has been given to the study of non-drug treatment methods, among which neuromodulation occupies a special place. Electrical stimulation of the cervical spinal cord has shown high efficacy in chronic migraine in the clinic, but the mechanisms of migraine neuromodulation have not been determined. This review describes the current understanding of the role of dopamine in the development of migraine, considers a new experimental model for studying the mechanisms of its development – animals with dopaminergic dysregulation, with dopamine transporter knockout (DAT-KO), describes possible mechanisms, prerequisites and experience of using spinal electrical stimulation for the treatment of migraine.

The article presents a summary and critical analysis of the literature data on neural interfaces mainly for the last five years. An examples, experimental findings, clinical outcomes of applications of neural interfaces aimed at enhancing human capabilities in interacting with the environment and leveraging advancements in electronics, nanoscale bioengineering, and artificial intelligence to improve quality of life or advance regenerative medicine are shown. The review highlights the most promising types of neural interfaces, with particular emphasis on invasive technologies and the application of cutting-edge developments in implantable materials characterized by high biocompatibility, long-term stability, and optimized biophysical properties. Materials for invasive technologies are evaluated in terms of their suitability for specific biomedical applications, accompanied by comparative analyses. Significant attention is devoted to emerging technologies in biomimetics and electrical biostimulation, as well as innovative approaches to the applied aspects of brain and spinal interfaces. Thus, this review serves as a valuable resource for students and professionals whose educational and career interests are focused on an in-depth exploration of neural interface technologies.