Neurotransmitter Systems Research Articles

Multifunctional, fluorene‐based modulator of cholinergic and GABAergic neurotransmission as a novel drug candidate for palliative treatment of Alzheimer’s disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia (BPSD). Given that cholinergic neurons are predominantly affected in AD, current treatments primarily aim to enhance cholinergic neurotransmission. However, imbalances in other neurotransmitters, such as γ‐aminobutyric acid (GABA), also contribute to AD symptomatology. In the presented research, by using a combination of crystallography and computational methods we developed 6 as a dual modulator of GABAergic and cholinergic neurotransmission systems. Compound 6 demonstrated inhibition of BuChE (IC50 = 0.21 μM) and GABA transporter 1 (IC50 = 10.96 μM) and 3 (IC50 = 7.76 μM), along with a favorable drug‐likeness profile. Subsequent in vivo studies revealed effectiveness of 6 in enhancing memory retention and alleviating anxiety and depression symptoms in animal models, while also proving safe and bioavailable for oral administration. The innovative multi‐target‐directed ligand 6 offers a new approach to treating cognitive deficits and BPSD in AD.

Single Intranasal Administration of Ucn3 Affects the Development of PTSD Symptoms in an Animal Model

Post-traumatic stress disorder (PTSD) is a multifactorial psychological disorder that affects different neurotransmitter systems, including the central CRH system. CRH acts via the CRHR1 and CRHR2 receptors, which exert opposite effects, i.e., anxiogenic or anxiolytic. The aim of this work was to investigate how intranasal administration of the CRHR2-specific agonist urocortin 2 (Ucn2) or urocortin 3 (Ucn3) affects manifestations of PTSD in a single prolonged stress (SPS) animal model of PTSD. Elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behavior. Changes in the gene expressions of CRH, CRHR1, CRHR2, glucocorticoid receptor (GR), and FKBP5 were measured in brain regions (BNST, amygdala, and PVN) responsible for modulating the stress response. The SPS animals spent less time in the OF central zone and were less mobile than the controls; however, the Ucn3 treatment reversed this effect. SPS decreased the GR and FKPB5 mRNA levels in the PVN. Ucn3 suppressed the effect of SPS on FKBP5 mRNA expression in the PVN and increased FKBP5 mRNA in the BNST and PVN compared to the stressed animals. We demonstrate that Ucn3 has the potential to ameliorate anxiety-like behavior in SPS animals and also to affect the neuroendocrine system in the BNST and PVN. In addition, we confirm the important role of CRHR2 signaling in mediating the stress response.

Hippocampus under pressure: molecular mechanisms of cognitive impairment in shr rats

In clinical studies and in animal experiments, data have been obtained indicating the association of chronic hypertension with the development of cognitive impairment. The review examines structural and biochemical changes in the hippocampus of SHR rats with genetic hypertension, which are used as a model of essential hypertension, as well as vascular dementia. The dysfunction of the hypothalamic-pituitary-adrenocortical system, observed in SHR rats at an early age, may, along with the development of hypertension, be a key factor in the damage to the hippocampus at the structural and molecular levels. Global changes at the body level (hypertension, neurohumoral dysfunction) are associated with the development of vascular pathology and destruction of the blood-brain barrier. Changes in multiple biochemical glucocorticoid-dependent processes in the hippocampus (dysfunction of steroid hormone receptors, disorders of neurotransmitter systems, BDNF deficiency, oxidative stress, neuroinflammation) are accompanied by structural changes including cellular processes of neuroinflammation (microgliosis, astrogliosis), disorders of neurogenesis in the subgranular neurogenic niche, neurodegenerative processes at the level of synapses, axons and dendrites up to neuronal cell death. The consequence of this is dysfunction of the hippocampus, a key structure of the limbic system necessary for the realization of cognitive functions. Summarizing of the available results at various levels, from the level of the organism and the structure of the brain (hippocampus) to the molecular one, allows us to confirm the translational validity of SHR rats for modeling the mechanisms of vascular dementia.

Effects of lateral ventricle injection of 5,7-dihydroxytryptamine on neurons in the medial prefrontal cortex of rats: An electrophysiology study

The medial prefrontal cortex (mPFC) is closely associated with various psychopathologies in humans, and its dysfunction is invariably accompanied by abnormalities in the serotonin (5-hydroxytryptamine, 5-HT) system of the brain. In this study, in-vivo extracellular recording techniques were used to investigate changes in the excitability of pyramidal neurons and interneurons in the rat mPFC following injection of 5,7-dihydroxytryptamine (5,7-DHT) into the bilateral lateral ventricles to damage the serotoninergic neurons. The levels of 5-HT in the mPFC and dorsal raphe nucleus of rats were determined by high-performance liquid chromatography. The results showed that the levels of 5-HT were significantly reduced in the mPFC and dorsal raphe nucleus two weeks after injection of 5,7-DHT into the bilateral lateral ventricles, relative to the normal group. The discharge frequency of pyramidal neurons in the mPFC was markedly increased compared to the normal group, with a significant rise in burst discharge, while the average discharge frequency of interneurons was significantly reduced and tended towards irregular activity. The results of the study indicated that the brain’s 5-HT neurotransmitter system not only directly affects the activity of mPFC pyramidal neurons but also modulates the electrical activity of interneurons, thereby regulating the local microcircuitry within the mPFC and participating in its function

The Role of the Vagus Nerve in the Microbiome and Digestive System in Relation to Epilepsy.

The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.

Harnessing Brain Plasticity: The Therapeutic Power of Repetitive Transcranial Magnetic Stimulation (rTMS) and Theta Burst Stimulation (TBS) in Neurotransmitter Modulation, Receptor Dynamics, and Neuroimaging for Neurological Innovations

Transcranial magnetic stimulation (TMS) methods have become exciting techniques for altering brain activity and improving synaptic plasticity, earning recognition as valuable non-medicine treatments for a wide range of neurological disorders. Among these methods, repetitive TMS (rTMS) and theta-burst stimulation (TBS) show significant promise in improving outcomes for adults with complex neurological and neurodegenerative conditions, such as Alzheimer’s disease, stroke, Parkinson’s disease, etc. However, optimizing their effects remains a challenge due to variability in how patients respond and a limited understanding of how these techniques interact with crucial neurotransmitter systems. This narrative review explores the mechanisms of rTMS and TBS, which enhance neuroplasticity and functional improvement. We specifically focus on their effects on GABAergic and glutamatergic pathways and how they interact with key receptors like N-Methyl-D-Aspartate (NMDA) and AMPA receptors, which play essential roles in processes like long-term potentiation (LTP) and long-term depression (LTD). Additionally, we investigate how rTMS and TBS impact neuroplasticity and functional connectivity, particularly concerning brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase receptor type B (TrkB). Here, we highlight the significant potential of this research to expand our understanding of neuroplasticity and better treatment outcomes for patients. Through clarifying the neurobiology mechanisms behind rTMS and TBS with neuroimaging findings, we aim to develop more effective, personalized treatment plans that effectively address the challenges posed by neurological disorders and ultimately enhance the quality of neurorehabilitation services and provide future directions for patients’ care.

Role of adenosine in the pathophysiology and treatment of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental condition characterized by persistent inattention, hyperactivity, and impulsivity. Although its precise etiology remains unclear, current evidence suggests that dysregulation within the neurotransmitter system plays a key role in the pathogenesis of ADHD. Adenosine, an endogenous nucleoside widely distributed throughout the body, modulates various physiological processes, including neurotransmitter release, sleep regulation, and cognitive functions through its receptors. This review critically examines the role of the adenosine system in ADHD, focusing on the links between adenosine receptor function and ADHD-related symptoms. Additionally, it explores how adenosine interacts with dopamine and other neurotransmitter pathways, shedding light on its involvement in ADHD pathophysiology. This review aims to provide insights into the potential therapeutic implications of targeting the adenosine system for ADHD management.

Abnormal Granger causal connectivity based on altered gray matter volume and associated neurotransmitters of adolescents with internet gaming disorder revealed by a multimodal neuroimaging study

Although prior studies have revealed alterations in gray matter volume (GMV) among individuals with internet gaming disorder (IGD). The brain's multifaceted functions hinge crucially on the intricate connections and communication among distinct regions. However, the intricate interaction of information between brain regions with altered GMV and other regions, and how they synchronize with various neurotransmitter systems, remains enigmatic. Therefore, we aimed to integrate structural, functional and molecular data to explore the GMV-based Granger causal connectivity abnormalities and their correlated neurotransmitter systems in IGD adolescents. Voxel-based morphometry (VBM) analysis was firstly performed to investigate GMV differences between 37 IGD adolescents and 35 matched controls. Brain regions with altered GMV were selected as seeds for further Granger causality analysis (GCA). Two-sample t tests were performed using the SPM12 toolkit to compare the GMV and Granger causal connectivity between IGD and control groups (GRF corrected, Pvoxel<0.005, Pcluster<0.05). Then, GMV-based Granger causal connectivity was spatially correlated with PET- and SPECT-derived maps covering multifarious neurotransmitter systems. Multiple comparison correction was performed using false discovery rate (FDR). Compared with controls, IGD adolescents showed higher GMV in the caudate nucleus and lingual gyrus. For the GCA, IGD adolescents showed higher Granger causal connectivity from insula, putamen, supplementary motor area (SMA) and middle cingulum cortex (MCC) to the caudate nucleus, and lower Granger causal connectivity from superior/inferior parietal gyrus (SPG/IPG) and middle occipital gyrus (MOG) to the lingual gyrus. Besides, GMV-based Granger causal connectivity of IGD adolescents were associated with the dopaminergic, serotonergic, GABAergic and noradrenaline systems. This study revealed that the caudate nucleus and lingual gyrus may be the key sites of neuroanatomical changes in IGD adolescents, and whole-brain Granger causal connectivity abnormalities based on altered GMV involved large brain networks including reward, cognitive control, and visual attention networks, and these abnormalities are associated with a variety of neurotransmitter systems, which may be associated with higher reward sensitivity, cognitive control, and attention control dysfunction.

Pharmacological manipulation of neurotransmitter activity induces disparate effects on cerebral blood flow and resting-state fluctuations

Abstract Functional MRI methods can assess aspects of drug-induced brain response. Resting blood oxygenation level dependent (BOLD) fMRI and arterial spin labeling (ASL) perfusion MRI indirectly measure brain function through the coupling of activity to cerebral blood flow (CBF) and oxygenation but their relative sensitivity has not been directly compared. We assessed changes in resting measures of BOLD and ASL MRI in response to two neurotransmitter modulators: citalopram, a selective serotonin reuptake inhibitor, and alprazolam, a positive allosteric modulator of GABA type A receptor. Thirty healthy subjects were imaged in a placebo-controlled study, with N=20 subjects receiving each treatment as part of an incomplete block design. Time-averaged CBF images from ASL and measures of resting-state fluctuations of BOLD and ASL images were assessed for significant effects. Following acute citalopram administration, analysis of the ASL data showed a reduction in time-averaged regional CBF in regions associated with high levels of 5-HT1A receptor density. In contrast, following alprazolam administration, BOLD amplitude of low frequency fluctuations showed a highly significant and cortically widespread increase, consistent with the distribution of GABA-A receptors. Only a marginal decrease in ASL CBF was detected after alprazolam intake. BOLD and ASL are each sensitive to drugs targeting neurotransmitter systems, but appear to reflect different aspects of neural metabolism and the balance between excitatory and inhibitory activity. Accordingly, their combination may best capture the effects of neurotransmitter modulations, and thus be advantageous for pharmacological MRI studies.

Neuroplasticity and Cocaine Exposure During Adolescence

The adolescent brain is particularly vulnerable to the effects of cocaine exposure due to ongoing neurodevelopment especially in areas that are crucial for cognitive and emotional regulation. This review explores the multifaceted impact of cocaine on neuroplasticity during adolescence, thereby highlighting both the immediate and long-term consequences of drug exposure. Key findings from recent studies indicate that cocaine use during adolescence leads to significant alterations in synaptic plasticity, dendritic spine morphology, and neurotransmitter systems, which may persist into adulthood and contribute to addictive behaviors. Additionally, the interaction between genetic predispositions, environmental stressors, and drug exposure is emphasized. The review also analyzed the risks of early-life stress and social isolation on cocaine-induced neuroplasticity, which can render anxiety-related behaviors and lead to neurological changes. Future studies should incorporate longitudinal design to understand the long-term trajectory of neuroplasticity induced by cocaine. This paper can provide some suggestions to the development of prevention and intervention programs for adolescents at risk.

Vitamin C improved anxiety and depression like behavior induced by chronic unpredictable mild stress in adolescent rats by influencing on oxidative stress balance, neurotransmitter systems, and inflammatory response

ABSTRACT Objectives: Stress is an adaptive response to different events in daily life that could strain physically, emotionally, or psychologically. Adolescence is an important developmental period due to physical, psychological, and social maturation. The aim of our study is to state whether chronic unpredictable mild stress (CUMS) during adolescence in male rats can cause anxiety and depression in adulthood and whether vitamin C (Vit C) can prevent this problem or not. Methods: For this purpose, we performed behavioral tests, including open field test, elevated plus maze, and forced swimming test. In addition, we investigated the metabolism of serotonin, the level of inflammation, oxidative stress and brain-derived neurotrophic factor (BDNF) in the brain cortex tissue of animals. Results: Results indicated that CUMS exacerbates mood-related behaviors by affecting the brain oxidative stress balance, inflammatory response, and serotonin metabolism. Moreover, we found that CUMS-Vit C co-treatment could significantly reverse CUMS-induced complications by restoration of the mentioned biochemical parameters. Discussion: Taken together, we would like to suggest the use of Vit C supplementation as a safe, inexpensive, and effective strategy for the management of CUMS.

Abnormal percent amplitude of fluctuation in patients with lifelong premature ejaculation is associated with neurotransmitter profiles.

Identifying additional imaging biomarkers of lifelong premature ejaculation (LPE) may provide valuable insights into understanding the underlying neural mechanisms of this disorder. Forty-six LPE patients and thirty-five healthy controls (HCs) were enrolled in this study. The Percent Amplitude of Fluctuation (PerAF) method was used to assess differences in brain function in LPE patients compared to HCs during the resting-state. Receiver operating characteristic (ROC) analysis was used to investigate the potential biomarkers based on the imaging findings. Correlation analysis was then applied to examine the relationships between the neuroimaging findings and clinical symptoms. We also investigated whether PerAF alterations in LPE patients were associated with specific neurotransmitter systems. Compared to HCs, LPE patients showed increased PerAF in the middle cingulate cortex (MCC), supramarginal gyrus, Rolandic operculum, parahippocampus/hippocampus (ParaHIPP/HIPP) as well as insula; and decreased PerAF in the precuneus, inferior temporal cortex plus occipital cortex. The MCC and ParaHIPP/HIPP exhibited higher classification performance on ROC analysis. Positive correlations were found between the Premature Ejaculation Diagnostic Tool score and PerAF in the insula, and the International Index of Erectile Function score and PerAF in the precuneus. Additionally, altered PerAF in LPE patients correlated significantly with the spatial distribution of dopamine, acetylcholine and epinephrine pathways. Our findings indicate that LPE patients have PerAF-related changes in certain brain regions associated with visual, sensory and/or emotional processing, and reveal that the abnormal control of ejaculatory function may be related to the combined dysregulation of neurotransmitter systems in LPE patients.

An overview of the pathophysiology of agitation in Alzheimer's dementia with a focus on neurotransmitters and circuits.

Alzheimer's dementia (AD) is a progressive, neurodegenerative disease often accompanied by neuropsychiatric symptoms that profoundly impact both patients and caregivers. Agitation is among the most prevalent and distressing of these symptoms and often requires treatment. Appropriate therapeutic interventions depend on understanding the biological basis of agitation and how it may be affected by treatment. This narrative review discusses a proposed pathophysiology of agitation in Alzheimer's dementia based on convergent evidence across research approaches. Available data indicate that agitation in Alzheimer's dementia is associated with an imbalance of activity between key prefrontal and subcortical brain regions. The monoamine neurotransmitter systems serve as key modulators of activity within these brain regions and circuits and are rendered abnormal in AD. Patients with AD who exhibited agitation symptoms during life have alterations in neurotransmitter nuclei and related systems when the brain is examined at autopsy. The authors present a model of agitation in Alzheimer's dementia in which noradrenergic hyperactivity along with serotonergic deficits and dysregulated striatal dopamine release contribute to agitated and aggressive behaviors.

Exploring the Frontier: The Human Microbiome’s Role in Rare Childhood Neurological Diseases and Epilepsy

Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut–brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this disease and other rare neurological diseases.

Abnormal EEG Effects of Acute Apomorphine Injection in 5xFAD Transgenic Mice Are Partially Normalized in Those Chronically Pretreated with Apomorphine: The Time–Frequency Clustering of EEG Spectra

Background: In experimental and clinical studies of pharmacological treatments for Alzheimer’s disease (AD), the electroencephalogram (EEG) frequency spectrum approach has demonstrated its efficacy in determining the characteristics of pathological changes in the functioning of different cerebral structures, interconnections between them, and disturbances in the brain neurotransmitter systems. The main results have been obtained in frames of traditionally used so-called “classical” EEG frequency bands: delta, theta, alpha, and beta. Objective: This unified approach simplifies comparing data from different studies but loses the dynamic peculiarities of the effects because of their time-dependent transition through the borders of the “classical” bands. Methods: In this study on non-narcotized freely moving 5xFAD transgenic mice, a model of AD, chronically pretreated with a non-selective dopamine (DA) receptor agonist, apomorphine (APO), we analyze the transitory EEG effects of acute APO injection in different brain areas by use of our “time–frequency” clustering program. The acute injection of APO was used to compare DA receptor sensitivity in 5xFAD mice pretreated with either APO or saline vs. wild-type (WT) mice pretreated with saline. Results: After acute APO injection, the clusters of enhanced EEG activity centered in the theta–alpha frequency range observed in WT mice disappeared in 5xFAD mice pretreated with saline and practically recovered in 5xFAD mice pretreated with APO. Conclusions: In 5xFAD mice pretreated with saline, the sensitivity of DA receptors was disturbed; chronic APO pretreatment mainly recovered this characteristic in 5xFAD mice. The “clustering” of pharmacological EEG effects and their time-dependent transition between classical frequency bands is a new effective approach for analyzing cerebral neurotransmission in neurodegenerative pathologies.

Unraveling the Relationship between Oral Habits and Anxiety: A Narrative Review

ABSTRACT This narrative review aims to elucidate the bidirectional relationship between oral habits and anxiety, examining potential underlying mechanisms, psychological factors, and clinical implications. A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus and Google Scholar, to identify relevant articles published in peer-reviewed journals. Studies investigating the relationship between oral habits (e.g., bruxism, nail biting) and anxiety disorders, as well as associated psychological factors, were included. Oral habits and anxiety exhibit a bidirectional relationship, with individuals engaging in oral habits as coping mechanisms to alleviate anxiety and stress, while anxiety can act as a precipitating factor for the development or exacerbation of oral habits. Common underlying mechanisms include dysregulation of the hypothalamic-pituitary-adrenal axis, alterations in neurotransmitter systems, and psychosocial factors. Psychological factors, such as cognitive-behavioral factors, emotional regulation, and attentional biases, further influence the manifestation and maintenance of both oral habits and anxiety. Understanding the complex interplay between oral habits and anxiety is crucial for holistic approaches to healthcare. Integrated assessment and management strategies are needed to address both conditions effectively, with emphasis on behavioral interventions, pharmacological approaches, and multidisciplinary collaboration between dental and mental health professionals. By recognizing and addressing the bidirectional nature of this relationship, healthcare providers can optimize patient care and improve overall well-being.

A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antipsychotic Drugs

Background: Psychosis is a debilitating mental disorder characterized by a profound disconnection from reality, manifesting in symptoms such as hallucinations, delusions, and disorganized thinking. The pathophysiology of psychosis is multifaceted, involving an interplay of neurobiological, genetic, and environmental factors. Neurobiologically, dysregulation of neurotransmitter systems particularly dopaminergic, serotonergic, and glutamatergic pathways-plays a central role, with excessive dopaminergic activity linked to positive symptoms and glutamatergic dysfunction implicated in cognitive impairments. Genetic predisposition, evidenced by significant heritability and associations with specific genetic variants, intersects with environmental factors such as stress, trauma, and substance use to influence the onset and progression of psychosis. Cognitive disruptions, including deficits in attention, memory, and executive function, exacerbate the disorder’s impact. This phenomenon has led to short-term as well as long-term psychosocial and mental health implications for all. Objective: To determine the antipsychotic activity of pharmaceuticals, numerous antipsychotic screening models are available. Determining the optimal animal model for measuring antipsychotic activity is the primary goal of this study. Methods: A search for literature was carried out using several keywords, including "Antipsychotic," "In-vivo models," "In-vitro models," and "Behavior models," on the databases Science Direct and PubMed. For the purpose of obtaining the most appropriate articles to fulfil the goal of this review article, the search was customized by using the necessary filters. Results: Research and review articles based on neuroleptic screening models are available to determine the antipsychotic activity of novel pharmacological compounds. Conclusion: Following our research, we identified several helpful models for evaluating the antipsychotic activity of pharmaceuticals and proposed that combining invitro and in-vivo techniques with behavioral methodologies might yield the most appropriate results for our field of study.

Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.

Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.

SCREENING STUDY OF THE PSYCHOTROPIC ACTIVITY OF NEUROPEPTIDE COMPOUNDS IN CONDITIONS OF MERCAZOLYL HYPOTHYROIDISM

Introduction. To date, there has been an increase in thyroid diseases mediated by a violation of regulatory mechanisms on the part of the central structures of the hypothalamic-pituitary-thyroid system. Numerous scientific studies have revealed that the emerging thyroid imbalance in thyroid diseases causes the development of metabolic syndrome, disorders of the cardiovascular system, as well as neuropsychic changes, which are often the first clinical manifestations of thyroid pathology. The current direction today is the study and development of means of correction of possible neuropsychic disorders. Of interest are the compounds of the peptide structure, on the basis of which effective drugs with a wide variety of pharmacological properties are being synthesized today. It has been proven that peptide compounds have neurotropic, psychotropic, anxiolytic, and other pharmacological effects due to their effect on the functional activity of neurotransmitter systems. The aim of the study was a screening study of the psychotropic activity of peptide compounds in conditions of hypofunction of the thyroid gland. Material and methods. The study was conducted on male rats divided into groups: I-th – control animals; II-th – individuals with induced hypothyroidism; III, IV, V, VI, VII and VIII-th – animals treated with hypothyroidism, respectively, Thr-Lys-Pro-Arg-Pro-Gly-Pro, ACTH(4-7)-Pro-Gly-Pro, ACTH(6-9)-Pro-Gly-Pro, Pro-Gly-Pro, Pro-Gly-Pro-Leu, Arg-Pro-Gly-Pro, Pro-Gly-Pro-Val and Met-Thr-Lys-Pro-Arg-Pro-Gly-Pro doses 87; 87; 89; 33; 44; 42; 42; 88 mcg/kg/day, which were 1/10 of the molecular weight of the studied substances. The psychotropic activity of the studied peptides was studied using the Open Field test. Results. It was found that in the conditions of experimental hypothyroidism, there is an inhibition of motor and exploratory activity against the background of an increase in anxiety levels (duration of freezing, grooming reactions and the number of defecations). The studied peptide compounds had a corrective effect to varying degrees on the psychoemotional state of laboratory animals in conditions of hypofunction of the thyroid gland. Conclusions. The results of a screening study in a number of regulatory peptides indicate that the compounds ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro have the most pronounced psychotropic activity in relation to behavioral indicators in the Open Field test under conditions of experimental hypothyroidism.

A neurotransmitter atlas of C. elegans males and hermaphrodites

Mapping neurotransmitter identities to neurons is key to understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In the Caenorhabditis elegans nervous system, neurotransmitter identities have been largely assigned by expression pattern analysis of neurotransmitter pathway genes that encode neurotransmitter biosynthetic enzymes or transporters. However, many of these assignments have relied on multicopy reporter transgenes that may lack relevant cis-regulatory information and therefore may not provide an accurate picture of neurotransmitter usage. We analyzed the expression patterns of 16 CRISPR/Cas9-engineered knock-in reporter strains for all main types of neurotransmitters in C. elegans (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, and octopamine) in both the hermaphrodite and the male. Our analysis reveals novel sites of expression of these neurotransmitter systems within both neurons and glia, as well as non-neural cells, most notably in gonadal cells. The resulting expression atlas defines neurons that may be exclusively neuropeptidergic, substantially expands the repertoire of neurons capable of co-transmitting multiple neurotransmitters, and identifies novel sites of monoaminergic neurotransmitter uptake. Furthermore, we also observed unusual co-expression patterns of monoaminergic synthesis pathway genes, suggesting the existence of novel monoaminergic transmitters. Our analysis results in what constitutes the most extensive whole-animal-wide map of neurotransmitter usage to date, paving the way for a better understanding of neuronal communication and neuronal identity specification in C. elegans.