Role In Neurotransmission Research Articles

Bulbospinal nociceptive ON and OFF cells related neural circuits and transmitters.

The rostral ventromedial medulla (RVM) is a bulbospinal nuclei in the descending pain modulation system, and directly affects spinal nociceptive transmission through pronociceptive ON cells and antinociceptive OFF cells in this area. The functional status of ON and OFF neurons play a pivotal role in pain chronification. As distinct pain modulative information converges in the RVM and affects ON and OFF cell excitability, neural circuits and transmitters correlated to RVM need to be defined for an in-depth understanding of central-mediated pain sensitivity. In this review, neural circuits including the role of the periaqueductal gray, locus coeruleus, parabrachial complex, hypothalamus, amygdala input to the RVM, and RVM output to the spinal dorsal horn are discussed. Meanwhile, the role of neurotransmitters is concluded, including serotonin, opioids, amino acids, cannabinoids, TRPV1, substance P and cholecystokinin, and their dynamic impact on both ON and OFF cell activities in modulating pain transmission. Via clarifying potential specific receptors of ON and OFF cells, more targeted therapies can be raised to generate pain relief for patients who suffer from chronic pain.

Antidepressant Effect of Alpha Lipoic Acid in Rats Exposed to Chronic Unpredictable Mild Stress: Putative Role of Neurotransmitters and 5HT3 Receptor

Depression is a neuropsychiatric disorder characterized by altered emotion and cognition. Alpha lipoic acid (ALA) is a potent natural antioxidant and exhibits neuroprotective effects. However, its antidepressant activity and its mechanism of action in rats exposed to chronic unpredictable mild stress (CUMS) need to be evaluated. The rats were divided into six groups. Group, I vehicle control (without stress), II- CUMS, III- fluoxetine (FLX) (50 mg/kg p.o.), IV, V, and VI were treated with ALA (50, 100, 200 mg/kg, p.o.), respectively. All the groups, except I, were subjected to CUMS + treatments from day 1 to day 42. Body weight and behavioral parameters like sucrose preference test (SPT), Morris water maze (MWM), resident intruder test (RIT), and marble-burying test (MBT) were performed on day 0, day 21, and day 42, and forced swim test (FST) on last day 42 and 43 only. The rats were further sacrificed for biochemical and histopathological evaluation. ALA significantly improved behavioral function, increased antioxidant strength, reduced lipid peroxidation, restored monoamines, and protected CA3 neurons. Further, docking studies revealed strong binding of ALA on the 5HT3 receptor. The study demonstrates that ALA might be exhibiting antidepressant effects in part by restoring monoamines and modulating the 5HT3 receptor.

Neural control of coronary artery blood flow by non-adrenergic and non-cholinergic mechanisms.

What is the topic of this review? How non-adrenergic, non-cholinergic neural mechanisms regulate coronary artery blood flow. What advances does it highlight? The main coronary arteries dynamically adapt to maintain adequate blood flow to the working myocardium. There is growing evidence for an important role of non-classic neurotransmitters in regulating coronary blood flow. This review highlights current evidence for non-adrenergic, non-cholinergic control of coronary artery blood flow and our understanding of the dynamics of this system. Blood flow through the coronary vasculature is essential to maintain myocardial function. As the metabolic demand of the heart increases, so does blood flow through the coronary arteries in a dynamic and adaptive manner. Several mechanisms, including local metabolic factors, mechanical forces and autonomic neural control, regulate coronary artery blood flow. To date, neural control has predominantly focused on the classical neurotransmitters of noradrenaline and acetylcholine. However, autonomic nerves, sympathetic, parasympathetic and sensory, release a variety of neurotransmitters that can directly affect the coronary vasculature. Reduced or altered coronary blood flow and autonomic imbalance are hallmarks of most cardiovascular diseases. Understanding the role of autonomic non-adrenergic, non-cholinergic cotransmitters in coronary blood flow regulation is fundamental to furthering our understanding of this vital system and developing novel targeted therapies.

Monoamine Neurotransmitters and Drug Addiction

Drug addiction is a chronic, relapsing brain disease. Various addictive drugs act on the reward circuit and eventually cause changes in the release of neurotransmitters, resulting in a rewarding effect. Among them, the monoamine neurotransmitters 5-hydroxytryptamine, norepinephrine and dopamine play an essential role in drug addiction. The role and mechanism of monoamine neurotransmitters in drug addiction are reviewed and discussed.

Neurotransmitters in Type 2 Diabetes and the Control of Systemic and Central Energy Balance.

Efficient signal transduction is important in maintaining the function of the nervous system across tissues. An intact neurotransmission process can regulate energy balance through proper communication between neurons and peripheral organs. This ensures that the right neural circuits are activated in the brain to modulate cellular energy homeostasis and systemic metabolic function. Alterations in neurotransmitters secretion can lead to imbalances in appetite, glucose metabolism, sleep, and thermogenesis. Dysregulation in dietary intake is also associated with disruption in neurotransmission and can trigger the onset of type 2 diabetes (T2D) and obesity. In this review, we highlight the various roles of neurotransmitters in regulating energy balance at the systemic level and in the central nervous system. We also address the link between neurotransmission imbalance and the development of T2D as well as perspectives across the fields of neuroscience and metabolism research.

Taxonomy of psychopathology based on a neurochemical framework

IntroductionTemperament and mental illness are considered to be variations along the same continuum of imbalance in the neurophysiological regulation of behaviour.ObjectivesThis presentation presents the benefits of constructivism approach to psychiatric taxonomies.MethodsThe presentation reviews findings in neurochemistry that link temperament traits in healthy individuals and symptoms of psychiatric disorders to complex relationships between neurotransmitter systems.ResultsSpecialization between neurotransmitter systems underlying temperament traits is analyzed here from a functional ecology perspective that considers the structure of adult temperament corresponding to the functional structure of human activities. In contrast to a more popular search for neuroanatomic biomarkers of psychopathology and temperament traits in healthy individuals, this presentation focuses on neurochemistry-based biomarkers. The roles of monoamine neurotransmitters (serotonin, dopamine, noradrenalin), as well as the roles of acetylcholine, neuropeptides and opioid receptor systems in the regulation of specific dynamical properties of behaviour are summarized within the neurochemical Functional Ensemble of Temperament (FET) model (Table 1) (Trofimova & Robbins, Neurosci Biobehav Rev, 2016, 64, 382-402; Trofimova, Neuropsychobiology, 2021, 80(2), 101-133).Image 2:ConclusionsThe FET framework allows having a neurochemistry-based structure of a taxonomy that can classify both, healthy bio-psychological traits and symptoms of psychopathology. The presentation will give examples of how the FET framework can be used in psychiatry and clinical psychology.Disclosure of InterestNone Declared

Tyrosinase Immobilization Strategies for the Development of Electrochemical Biosensors-A Review.

The development of enzyme biosensors has successfully overcome various challenges such as enzyme instability, loss of enzyme activity or long response time. In the electroanalytical field, tyrosinase is used to develop biosensors that exploit its ability to catalyze the oxidation of numerous types of phenolic compounds with antioxidant and neurotransmitter roles. This review critically examines the main tyrosinase immobilization techniques for the development of sensitive electrochemical biosensors. Immobilization strategies are mainly classified according to the degree of reversibility/irreversibility of enzyme binding to the support material. Each tyrosinase immobilization method has advantages and limitations, and its selection depends mainly on the type of support electrode, electrode-modifying nanomaterials, cross-linking agent or surfactants used. Tyrosinase immobilization by cross-linking is characterized by very frequent use with outstanding performance of the developed biosensors. Additionally, research in recent years has focused on new immobilization strategies involving cross-linking, such as cross-linked enzyme aggregates (CLEAs) and magnetic cross-linked enzyme aggregates (mCLEAs). Therefore, it can be considered that cross-linking immobilization is the most feasible and economical approach, also providing the possibility of selecting the reagents used and the order of the immobilization steps, which favor the enhancement of biosensor performance characteristics.

Enteric neuroanatomy and smooth muscle activity in the western diamondback rattlesnake (Crotalus atrox)

BackgroundGastrointestinal (GI) functions are controlled by the enteric nervous system (ENS) in vertebrates, but data on snakes are scarce, as most studies were done in mammals. However, the feeding of many snakes, including Crotalus atrox, is in strong contrast with mammals, as it consumes an immense, intact prey that is forwarded, stored, and processed by the GI tract. We performed immunohistochemistry in different regions of the GI tract to assess the neuronal density and to quantify cholinergic, nitrergic, and VIPergic enteric neurons. We recorded motility patterns and determined the role of different neurotransmitters in the control of motility. Neuroimaging experiments complemented motility findings.ResultsA well-developed ganglionated myenteric plexus (MP) was found in the oesophagus, stomach, and small and large intestines. In the submucous plexus (SMP) most neurons were scattered individually without forming ganglia. The lowest number of neurons was present in the SMP of the proximal colon, while the highest was in the MP of the oesophagus. The total number of neurons in the ENS was estimated to be approx. 1.5 million. In all regions of the SMP except for the oesophagus more nitric oxide synthase+ than choline-acetyltransferase (ChAT)+ neurons were counted, while in the MP ChAT+ neurons dominated. In the SMP most nerve cells were VIP+, contrary to the MP, where numerous VIP+ nerve fibers but hardly any VIP+ neuronal cell bodies were seen. Regular contractions were observed in muscle strips from the distal stomach, but not from the proximal stomach or the colon. We identified acetylcholine as the main excitatory and nitric oxide as the main inhibitory neurotransmitter. Furthermore, 5-HT and dopamine stimulated, while VIP and the ß-receptor-agonist isoproterenol inhibited motility. ATP had only a minor inhibitory effect. Nerve-evoked contractile responses were sodium-dependent, insensitive to tetrodotoxin (TTX), but sensitive to lidocaine, supported by neuroimaging experiments.ConclusionsThe structure of the ENS, and patterns of gastric and colonic contractile activity of Crotalus atrox are strikingly different from mammalian models. However, the main excitatory and inhibitory pathways appear to be conserved. Future studies have to explore how the observed differences are an adaptation to the particular feeding strategy of the snake.

Sex-dimorphic hindbrain lactate regulation of ventromedial hypothalamic nucleus glucoregulatory neuron 5’-AMP-activated protein kinase activity and transmitter marker protein expression

BackgroundThe oxidizable glycolytic end-product L-lactate is a gauge of nerve cell metabolic fuel stability that metabolic-sensory hindbrain A2 noradrenergic neurons impart to the brain glucose-regulatory network. Current research investigated the premise that hindbrain lactate deficiency exerts sex-specific control of energy sensor and transmitter marker protein responses to hypoglycemia in ventromedial hypothalamic nucleus (VMN) glucose-regulatory nitrergic and γ-aminobutyric acid (GABA) neurons. MethodsNitric oxide synthase (nNOS)- or glutamate decarboxylase65/67 (GAD)-immunoreactive neurons were laser-catapult-microdissected from male and female rat VMN after subcutaneous insulin injection and caudal fourth ventricular L-lactate or vehicle infusion for Western blot protein analysis. ResultsHindbrain lactate repletion reversed hypoglycemia-associated augmentation (males) or inhibition (females) of nitrergic neuron nNOS expression, and prevented up-regulation of phosphorylated AMPK 5’-AMP-activated protein kinase (pAMPK) expression in those neurons. Hypoglycemic suppression of GABAergic neuron GAD protein was averted by exogenous lactate over the rostro-caudal length of the male VMN and in the middle region of the female VMN. Lactate normalized GABA neuron pAMPK profiles in hypoglycemic male (caudal VMN) and female (all VMN segments) rats. Hypoglycemic patterns of norepinephrine (NE) signaling were lactate-dependent throughout the male VMN, but confined to the rostral and middle female VMN. ConclusionsResults document, in each sex, regional VMN glucose-regulatory transmitter responses to hypoglycemia that are controlled by hindbrain lactate status. Hindbrain metabolic-sensory regulation of hypoglycemia-correlated nitric oxide or GABA release may entail AMPK-dependent mechanisms in specific VMN rostro-caudal segments in each sex. Additional effort is required to examine the role of hindbrain lactoprivic-sensitive VMN neurotransmitters in lactate-mediated attenuation of hypoglycemic hyperglucagonemia and hypercorticosteronemia in male and female rats.

Imaging of glutamate in acute carbon monoxide poisoning using chemical exchange saturation transfer.

This study adopted the Glutamate Chemical Exchange Saturation Transfer (GluCEST) imaging technique to quantitatively analyze cranial glutamate and discussed the effectiveness of GluCEST values in identifying the pathogenesis of encephalopathy after CO poisoning. The routine MRI and functional MRI scans of two cohorts of subjects (CO group, n = 29; Control group, n = 21) were performed. Between-group comparisons were conducted for GluCEST% in regions of interest (ROI), including the basal ganglia, the thalamus, the frontal lobe, the occipital lobe, the genu of corpus callosum, the cingulate gyrus, and the cuneus. Moreover, an age-stratified subgroup analysis was devised, and a correlational analysis was performed for GluCEST% in each ROI, including the time in coma, Simple Mini-Mental State Examination Scale (MMSE) score, Hamilton Anxiety Scale score, and blood COHb%. As compared to the healthy control, the CO group led to significantly increasing GluCEST% in the basal ganglia, the occipital lobe, the genu of the corpus callosum, the cingulate gyrus, and the cuneus (p < 0.05). In the subgroup analysis for age, adult patients had higher GluCEST% in the basal ganglia, the thalamus, the occipital lobe, the cingulate gyrus, and the cuneus compared to healthy adults (p < 0.05). In addition, the correlational analysis of CO-poisoned patients revealed a statistical association between the GluCEST% and the MMSE in the thalamus and the genu of the corpus callosum. The GluCEST technique is superior to routine MRI in that it can identify the cerebral biochemical changes sooner after acute CO poisoning, which is significant for our understanding of the role of neurotransmitters in the pathological basis of this disease. Brain injury caused by CO poisoning may be different in adults and children.

Pentameric ligand gated ion channels' intracellular domain interaction with RIC3 chaperone.

Pentameric ligand-gated ion channels (pLGICs) are cys-loop receptors important in transduction of electrical signals between neurons in the peripheral and central nervous system. Their significant role in neurotransmission has increased the research in neuropharmacology. Members of this protein family are found in mammals, but also in prokaryotes that can often incorporate additional domains whose roles are largely uncharacterized. pLGICs include nicotinic acetylcholinereceptors, gamma-amino butyric acid A receptors, glycine receptors and type 3 serotonin receptors (5HT3). These receptors are integral membrane protein complexes composed of five subunits that surround the central pore. Each subunit incorporates a large extracellular domain which contains the agonist-binding site, four transmembrane segments (TM1-4) which form the ion pore, a large intracellular domain (ICD) between TM3 and TM4, and a short extracellular C-terminal region. The ionotropic serotonin subtype-3 (5-HT3) receptor is of current interest as a therapeutic target in the treatment of alcohol abuse. Selective pharmacological antagonists reduce alcohol consumption in preclinical and clinical models. To date only two applications have been fully realized in the clinic: the treatment of emesis and irritable-bowel syndrome. Competitive antagonists, called setrons, target 5HT3R, are used in the management of nausea and vomiting associated with radiation and chemotherapies in cancer patients. These drugs interact with off-target subunits of the receptor and consequently lead to many undesired effects including headache and drowsiness. In order to understand and characterize effective control of neurotransmitter-gated pLGICs, we have explored the interaction of 5HT3R with RIC-3 chaperone which mediates functional expression of the channels. In the present study, synthetic pLGIC peptides were used to probe and characterize the interaction with RIC-3 in native sources such as mouse brains and neuronal cell lines.

Exploring the Role of Neurotransmitters in Multiple Sclerosis: An Expanded Review

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Although emerging evidence has shown that changes in neurotransmitter levels in the synaptic gap may contribute to the pathophysiology of MS, their specific role has not been elucidated yet. In this review, we aim to analyze preclinical and clinical evidence on the structural and functional changes in neurotransmitters in MS and critically discuss their potential role in MS pathophysiology. Preclinical studies have demonstrated that alterations in glutamate metabolism may contribute to MS pathophysiology, by causing excitotoxic neuronal damage. Dysregulated interaction between glutamate and GABA results in synaptic loss. The GABAergic system also plays an important role, by regulating the activity and plasticity of neural networks. Targeting GABAergic/glutamatergic transmission may be effective in fatigue and cognitive impairment in MS. Acetylcholine (ACh) and dopamine can also affect the T-mediated inflammatory responses, thereby being implicated in MS-related neuroinflammation. Also, melatonin might affect the frequency of relapses in MS, by regulating the sleep-wake cycle. Increased levels of nitric oxide in inflammatory lesions of MS patients may be also associated with axonal neuronal degeneration. Therefore, neurotransmitter imbalance may be critically implicated in MS pathophysiology, and future studies are needed for our deeper understanding of their role in MS.

Communication of gut microbiota and brain via immune and neuroendocrine signaling.

The gastrointestinal tract of the human is inhabited by about 5 × 1013 bacteria (of about 1,000 species) as well as archaea, fungi, and viruses. Gut microbiota is known to influence the host organism, but the host may also affect the functioning of the microbiota. This bidirectional cooperation occurs in three main inter-organ signaling: immune, neural, and endocrine. Immune communication relies mostly on the cytokines released by the immune cells into circulation. Also, pathogen-associated or damage-associated molecular patterns (PAMPs or DAMPs) may enter circulation and affect the functioning of the internal organs and gut microbiota. Neural communication relies mostly on the direct anatomical connections made by the vagus nerve, or indirect connections via the enteric nervous system. The third pathway, endocrine communication, is the broadest one and includes the hypothalamic-pituitary-adrenal axis. This review focuses on presenting the latest data on the role of the gut microbiota in inter-organ communication with particular emphasis on the role of neurotransmitters (catecholamines, serotonin, gamma-aminobutyric acid), intestinal peptides (cholecystokinin, peptide YY, and glucagon-like peptide 1), and bacterial metabolites (short-chain fatty acids).

Norepinephrine inhibits CD8+ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma

BackgroundMental stress-induced neurotransmitters can affect the immune system in various ways. Therefore, a better understanding of the role of neurotransmitters in the tumour immune microenvironment is expected to promote the development of novel anti-tumour therapies.MethodsIn this study, we analysed the plasma levels of neurotransmitters in anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb)-resistance patients and sensitive patients, to identify significantly different neurotransmitters. Subsequently, animal experiments and experiments in vitro were used to reveal the specific mechanism of norepinephrine’s (NE) effect on immunotherapy.ResultsThe plasma NE levels were higher in anti-PD-1 mAb-resistance patients, which may be the main cause of anti-PD-1 mAb resistance. Then, from the perspective of the immunosuppressive microenvironment to explore the specific mechanism of NE-induced anti-PD-1 mAb resistance, we found that NE can affect the secretion of C-X-C Motif Chemokine Ligand 9 (CXCL9) and adenosine (ADO) in tumour cells, thereby inhibiting chemotaxis and function of CD8+ T cells. Notably, the WNT7A/β-catenin signalling pathway plays a crucial role in this progression.ConclusionNE can affect the secretion of CXCL9 and ADO in tumour cells, thereby inhibiting chemotaxis and the function of CD8+ T cells and inducing anti-PD-1 mAb resistance in lung adenocarcinoma (LUAD).

Group I Metabotropic Glutamate Receptors Modulate Motility and Enteric Neural Activity in the Mouse Colon.

Glutamate is the major excitatory neurotransmitter in the central nervous system, and there is evidence that Group-I metabotropic glutamate receptors (mGlu1 and mGlu5) have established roles in excitatory neurotransmission and synaptic plasticity. While glutamate is abundantly present in the gut, it plays a smaller role in neurotransmission in the enteric nervous system. In this study, we examined the roles of Group-I mGlu receptors in gastrointestinal function. We investigated the expression of Grm1 (mGlu1) and Grm5 (mGlu5) in the mouse myenteric plexus using RNAscope in situ hybridization. Live calcium imaging and motility analysis were performed on ex vivo preparations of the mouse colon. mGlu5 was found to play a role in excitatory enteric neurotransmission, as electrically-evoked calcium transients were sensitive to the mGlu5 antagonist MPEP. However, inhibition of mGlu5 activity did not affect colonic motor complexes (CMCs). Instead, inhibition of mGlu1 using BAY 36-7620 reduced CMC frequency but did not affect enteric neurotransmission. These data highlight complex roles for Group-I mGlu receptors in myenteric neuron activity and colonic function.

Role of neurotransmitters and intestinal microbiota in pathogenesis of atopic dermatitis

Role of neurotransmitters and intestinal microbiota in pathogenesis of atopic dermatitis

The role of certain neurotransmitters in the emergence and progression of malignant tumors, and the potential of using neurotransmitter antagonists to block the carcinogenic effect of the tumor stroma

The role of certain neurotransmitters in the emergence and progression of malignant tumors, and the potential of using neurotransmitter antagonists to block the carcinogenic effect of the tumor stroma

CLINICAL AND SOCIAL CHARACTERISTICS AND FEATURES OF BIOCHEMICAL INDICATORS IN PERSONS WITH MENTAL DISORDERS WHO HAVE COMMITTED VIOLENT CRIMES

The relevance of the study is conditioned by the need to develop effective methods to prevent public danger arising from persons suffering from mental disorders, with identification of factors that influence aggressive behavior formation in order to improve measures to prevent crimes related to violence. the purpose of this work was to study the socio-demographic, clinical and psychopathological features and biochemical parameters in persons with mental disorders who committed violent crimes. the scientific novelty is determined by the importance of establishing the features of the complex influence of clinical, biological and social factors on the tendency to heteroaggression, the lack of scientifically substantiated data on the role of neurotransmitter and hormonal systems in aggressive behavior formation in patients with severe forms of mental pathology. Materials and methods. the research sample consisted of 100 respondents aged 18 to 60 years with a verified diagnosis of a severe mental disorder and the fact of criminal prosecution for violent crimes. the clinical features of the patients were evaluated using a clinical-psychopathological method with identification of the leading characteristics in psychopathological symptoms and syndromes. Standardized assessment of clinical characteristics was provided by the use of the psychometric methodology "Positive and Negative Syndrome Scale" (PANSS), the methodology "Structured Assessment of Unsafe Behavior Risk" (SOROP). for laboratory testing, blood and urine samples were used to determine the levels of serotonin, dopamine, cortisol, testosterone, free T3 (free T3), estradiol. Results. the most common clinical and social characteristics of persons with severe mental disorders and persistent aggressive criminal behavior were identified and described. in the majority of respondents, the indicators of the neurotransmitter system (serotonin, dopamine levels) were found to differ significantly from the reference values. a negative correlation was determined between serotonin excretion and the sum of points according to SOROP technique, as well as the subscale of aggression, which is part of the indicators in PANSS technique. Conclusions. the obtained data contribute to understanding the nature of heteroaggression in persons with mental disorders, indicating the need for further studying the relationship of social, clinical and biological parameters, determining their role in aggressive behavior formation in this contingent of patients.

Animal models of Obsessive-Compulsive Disorder (OCD)

Treatment developments, brain imaging studies, and results of pharmacological research elicit revision of related pathological theories to Obsessive-compulsive disorder (OCD) and new research patterns. One of the important and alluring new research patterns under the neurobiological approach corresponding to the pathology and treatment of obsessive-compulsive disorder (OCD) is animal models which are used in this disorder. Insomuch, many endeavors have been applied in order to expand animal models of OCD during recent 30 years. In the hope of, increasing our understanding and knowledge about pathology as well as the treatment of this disorder. By considering the methodology of developing obsessive behaviors in animals, OCD animal models are divided into three classifications behavioral, pharmacological, and genetic. Research and studies using different animal models indicate the role of the serotonin neurotransmitter particularly the 5-HT2c receptor, the Dopamine neurotransmitter particularly the D1 and D2 receptors, and at the less level the role of the NMDA receptor of the Glutamate neurotransmitter in the pathology of OCD disorder.

The role of neurotransmitters and indicators of oxidative stress in the formation of disorders of central conductive structures in patients who came into contact with metallic mercury

Introduction. Studies of toxic lesions due to exposure to metallic mercury compounds do not allow us to identify the features of the violation of central afferent conducting structures in the long-term period of chronic mercury intoxication (CHMI). The contribution of various systems to the development of pathology is not sufficiently disclosed. The study aims to identify the role of neurotransmitters in pathological changes in central hemodynamics, the value of lipid peroxidation products and the activity of antioxidant protection in the demyelination of central afferent conductive structures in workers exposed to metallic mercury in the workplace. Materials and methods. The authors examined 47 people (group one) - trained chemical production workers exposed to metallic mercury, and group two (51 people) - patients in the long-term period of CHMI. The control group (CG) consisted of 30 people who had no contact with toxicants. We have determined concentration of neurotransmitters, lipid peroxidation products (LPP), superoxide dismutase (SOD) and reduced glutathione (RG), nitric oxide. Results. Experts observed statistically significant changes in indicators in subgroups with and without changes in cerebral hemodynamics and in group two when compared with group one. Comparison of persons with CHMI without changes in blood circulation with the presence of disorders revealed an increase in normetanephrine in the latter, a decrease in NT-3. Correlation analysis showed: in group jne, there was a statistically significant difference between the vasomotor reactivity index (VRI) and serotonin. In group two - between CHMI and serotonin, adrenaline and dopamine. Changes in afferent pathways are interrelated with indicators of oxidative stress. Violations are accompanied by the formation of a pathological system, are signs of dysregulatory pathology. Limitations. The disadvantage of the study is the fact that scientists determined the content of neurotransmitters and products of lipid peroxidation and antioxidant protection in the blood of the subjects, and not in the structures of the brain. Conclusion. The increased content of biogenic amines leads to a change in peripheral blood circulation and regulation of cerebral blood flow by pressor action on the regulation of the vascular bed, leading to vasoconstriction, changes in the bioelectric activity of the structures of the reticular formation of the midbrain, hypothalamus, thalamocortical structures, most pronounced in the long-term period of chronic mercury intoxication. We found that the formation of demyelination in patients with chronic mercury intoxication was accompanied by a decrease in the concentration of NT-3. It was natural to reduce the level of reduced glutathione and superoxide dismutase in neurodegenerative processes in trained workers exposed to metallic mercury at work, and in patients with a long period of chronic mercury intoxication. Ethics. The study was conducted in compliance with the principles of the Helsinki Declaration of the World Association "Ethical principles of conducting Scientific medical research with human participation" (as amended in 2008), "Rules of Clinical Practice in the Russian Federation" (approved by the Order of the Ministry of Health of the Russian Federation dated 06/19/2003 No. 266).