Types Of Neurotransmitters Research Articles

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.

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.

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 C. 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. 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 neurons that uptake monoaminergic neurotransmitters. 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.

Dip2a regulates stress susceptibility in the basolateral amygdala.

JOURNAL/nrgr/04.03/01300535-202506000-00025/figure1/v/2024-08-05T133530Z/r/image-tiff Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post-traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A (Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid-associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

Power consumption during forward locomotion of C. elegans: an electrical circuit simulation

Biological neuronal networks are of great interest for emerging technological approaches such as neuromorphic engineering due to their capability to efficiently process information. To understand the principles governing this energy efficiency, it is useful to investigate model organisms with small and well-characterized neuronal networks. Caenorhabditis elegans (C. elegans) is such a model organism and perfectly suited for this purpose, because its neuronal network consists of only 302 neurons whose interconnections are known. In this work, we design an ideal electrical circuit modeling this neuronal network in combination with the muscles it controls. We simulate this circuit by a run-time efficient wave digital algorithm. This allows us to investigate the energy consumption of the network occurring during locomotion of C. elegans and hence deduce potential design principles from an energy efficiency point of view. Simulation results verify that a locomotion is indeed generated. We conclude from the corresponding energy consumption rates that a small number of neurons in contrast to a high number of interconnections is favorable for consuming only little energy. This underlines the importance of interneurons. Moreover, we find that gap junctions are a more energy-efficient connection type than synapses, and inhibitory synapses consume more energy than excitatory ones. However, the energetically cheapest connection types are not the most frequent ones in C. elegans’ neuronal network. Therefore, a potential design principle of the network could be a balance between low energy costs and a certain functionality.Graphical abstractEnergy consumption rates during forward locomotion of C. elegans. a Rates for the ion channels of all neurons, and b average rates for ion channels of a single, active neuron. c Comparison of average rates with respect to the number of active sensory, motor, and interneurons. d Rates for all gap junctions and synapses, and e rates for all synapses of a specific neurotransmitter type. f Average rates for a single synaptic or gap junctions connection vs the total number of connections present for the type of connection (i.e. ACh-synapse, GABA-synapse, Glu-synapse, gap junction).

On-Site Formation of Functional Dopaminergic Presynaptic Terminals on Neuroligin-2-Modified Gold-Coated Microspheres.

Advancements in neural interface technologies have enabled the direct connection of neurons and electronics, facilitating chemical communication between neural systems and external devices. One promising approach is a synaptogenesis-involving method, which offers an opportunity for synaptic signaling between these systems. Janus synapses, one type of synaptic interface utilizing synaptic cell adhesion molecules for interface construction, possess unique features that enable the determination of location, direction of signal flow, and types of neurotransmitters involved, promoting directional and multifaceted communication. This study presents the first successful establishment of a Janus synapse between dopaminergic (DA) neurons and abiotic substrates by using a neuroligin-2 (NLG2)-mediated synapse-inducing method. NLG2 immobilized on gold-coated microspheres can induce synaptogenesis upon contact with spatially isolated DA axons. The induced DA Janus synapses exhibit stable synaptic activities comparable to that of native synapses over time, suggesting their suitability for application in neural interfaces. By calling for DA presynaptic organizations, the NLG2-immobilized abiotic substrate is a promising tool for the on-site detection of synaptic dopamine release.

The Role of Neurotransmitters in Relation to Psychiatric Conditions Throughout the COVID-19 Epidemic

Various studies have reported the presence of psychiatric symptoms among individuals diagnosed with COVID-19, encompassing heightened stress levels, impaired cognitive function, depressive mood, anxiousness, post-traumatic stress disorder (PTSD), psychotic symptoms, and suicidal ideation. The objective of this review was to elucidate the involvement of neurotransmitters in psychiatric disorders following the COVID-19 pandemic. There are multiple variables that can influence the results of research studies examining the presence of symptoms or the initiation of psychiatric disorders in individuals diagnosed with COVID-19. Factors associated with mental health difficulties include direct involvement in the healthcare field, presence of a psychiatric disease within the family, limited social support, advanced age, solitary living arrangements, and the utilization of high dosages of steroids during the acute phase. Multiple types of neurotransmitters are involved in the modulation of stress levels inside the human body. The neurotransmitters implicated in this process include dopamine, serotonin, epinephrine and norepinephrine, acetylcholine, gamma-aminobutyric acid (GABA), and glutamate. In summary, cytokines have a pivotal role in modulating the hypothalamic-pituitary-adrenal (HPA) axis within the brain, hence potentially giving rise to psychiatric manifestations including impaired sleep, heightened stress, depressive affect, and several other psychological disturbances.

Trainable Bilingual Synaptic Functions in Bio-enabled Synaptic Transistors.

The signal transmission of the nervous system is regulated by neurotransmitters. Depending on the type of neurotransmitter released by presynaptic neurons, neuron cells can either be excited or inhibited. Maintaining a balance between excitatory and inhibitory synaptic responses is crucial for the nervous system's versatility, elasticity, and ability to perform parallel computing. On the way to mimic the brain's versatility and plasticity traits, creating a preprogrammed balance between excitatory and inhibitory responses is required. Despite substantial efforts to investigate the balancing of the nervous system, a complex circuit configuration has been suggested to simulate the interaction between excitatory and inhibitory synapses. As a meaningful approach, an optoelectronic synapse for balancing the excitatory and inhibitory responses assisted by light mediation is proposed here by deploying humidity-sensitive chiral nematic phases of known polysaccharide cellulose nanocrystals. The environment-induced pitch tuning changes the polarization of the helicoidal organization, affording different hysteresis effects with the subsequent excitatory and inhibitory nonvolatile behavior in the bio-electrolyte-gated transistors. By applying voltage pulses combined with stimulation of chiral light, the artificial optoelectronic synapse tunes not only synaptic functions but also learning pathways and color recognition. These multifunctional bio-based synaptic field-effect transistors exhibit potential for enhanced parallel neuromorphic computing and robot vision technology.

Profiling neurotransmitter-evoked glial responses by RNA-sequencing analysis.

Fundamental properties of neurons and glia are distinctively different. Neurons are excitable cells that transmit information, whereas glia have long been considered as passive bystanders. Recently, the concept of tripartite synapse is proposed that glia are structurally and functionally incorporated into the synapse, the basic unit of information processing in the brains. It has then become intriguing how glia actively communicate with the presynaptic and postsynaptic compartments to influence the signal transmission. Here we present a thorough analysis at the transcriptional level on how glia respond to different types of neurotransmitters. Adult fly glia were purified from brains incubated with different types of neurotransmitters ex vivo. Subsequent RNA-sequencing analyses reveal distinct and overlapping patterns for these transcriptomes. Whereas Acetylcholine (ACh) and Glutamate (Glu) more vigorously activate glial gene expression, GABA retains its inhibitory effect. All neurotransmitters fail to trigger a significant change in the expression of their synthesis enzymes, yet Glu triggers increased expression of neurotransmitter receptors including its own and nAChRs. Expressions of transporters for GABA and Glutamate are under diverse controls from DA, GABA, and Glu, suggesting that the evoked intracellular pathways by these neurotransmitters are interconnected. Furthermore, changes in the expression of genes involved in calcium signaling also functionally predict the change in the glial activity. Finally, neurotransmitters also trigger a general metabolic suppression in glia except the DA, which upregulates a number of genes involved in transporting nutrients and amino acids. Our findings fundamentally dissect the transcriptional change in glia facing neuronal challenges; these results provide insights on how glia and neurons crosstalk in a synaptic context and underlie the mechanism of brain function and behavior.

Neurotransmitter Systems in the Etiology of Major Neurological Disorders: Emerging Insights and Therapeutic Implications.

Neurotransmitters serve as chemical messengers playing a crucial role in information processing throughout the nervous system, and are essential for healthy physiological and behavioural functions in the body. Neurotransmitter systems are classified as cholinergic, glutamatergic, GABAergic, dopaminergic, serotonergic, histaminergic, or aminergic systems, depending on the type of neurotransmitter secreted by the neuron, allowing effector organs to carry out specific functions by sending nerve impulses. Dysregulation of a neurotransmitter system is typically linked to a specific neurological disorder. However, more recent research points to a distinct pathogenic role for each neurotransmitter system in more than one neurological disorder of the central nervous system. In this context, the review provides recently updated information on each neurotransmitter system, including the pathways involved in their biochemical synthesis and regulation, their physiological functions, pathogenic roles in diseases, current diagnostics, new therapeutic targets, and the currently used drugs for associated neurological disorders. Finally, a brief overview of the recent developments in neurotransmitter-based therapeutics for selected neurological disorders is offered, followed by future perspectives in that area of research.

In-silico Studies on Phthalimide GABA Analogs for Anticonvulsant Activity Against Sodium Channel and GABA-AT

Introduction: GABA is a type of inhibitory neurotransmitter; it blocks or inhibits certain nerve transmission. Our nervous system is calmed by GABA, thus preventing excessive fear or anxiety is a simple and rapid approach to raise and maintain healthy mental health. Some medical conditions associated with a change in the level of GABA are anxiety and mood disorders, schizophrenia, autism spectrum disorder, depression, epilepsy, and seizures. The aim of this study to increase the activity of GABA which can be enhanced by the incorporation of anthracene, phthalimide, benzene, and thalidomide. Materials and methods: Insilico Docking study was carried out by using Auto Dock 4.0 against GABA-AT protein and the binding energy was found out to be -7.61kcal/mol. GABA-Phthalimide substitution, derivatives were designed as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. The phthalimide pharmacophores interaction with voltage dependent sodium channels in neurons was investigated. Results and conclusion: This suggests the substitution of GABA as a possible lead compound. Therefore, in the present study, N, N-phthaloyl GABA combine with aniline a Noval compound 4-(1,3-dioxoisoindolin-2-yl)-N-phenylbutanamide is designed with improved anticonvulsant properties.

Quasi-LPV positive observer-based control of closed-loop deep brain stimulation systems

Parkinson’s disease is a neurodegenerative disorder in which dopamine (a specific type of neurotransmitter) production by neurons is destroyed in the brain. Therefore, there is less or no production of dopamine in the human brain and the patient has motor and non-motor complications. The main reason for Parkinson’s disease is the basal ganglia (BG) system imbalance. Therefore, it is imperative to find effective control methods to stabilize and regulate the BG system. To control the BG system within the normal oscillating performance, the opinion of closed-loop deep brain stimulation (DBS) system is used as the most innovative surgical treatment. In this paper, a quasi-linear parameter-varying (LPV) model is extracted from two known nonlinear models (the RT model and the modified RT model with 19 dynamics as the state variables of the BG system) as a comprehensive model to result in a more accurate control for the DBS system. The theoretical contributions in this paper are novel because this model is considered as a positive system and the related theories and properties are discussed. In view of this, quasi-LPV positive observer-based control method is designed for two situations; when all parameters are available for estimation (exact observer) and when all accurate parameters cannot be easily accessed (inexact observer). By designing such controllers, the provided algorithm does not need the availability of the scheduling parameters of the model, which is the novel challenge of this paper. The positivity and asymptotic stability of the proposed controllers have been studied based on linear matrix inequalities. The feasibility of the proposed closed-loop system and the effectiveness of the controllers are verified by numerical simulation. The designed controllers make the closed-loop DBS system stable and positive in both situations. It is while, without this controller, there is no such oscillating performance for Parkinsonian patients.

Analytical approaches to examine gamma-aminobutyric acid and glutamate vesicular co-packaging.

Multi-transmitter neurons, i.e., those that release more than one type of neurotransmitter, have been found in many organisms and brain areas. Given the peculiar biology of these cells, as well as the potential for diverse effects of each of the transmitters released, new tools, and approaches are necessary to parse the mechanisms and functions of synaptic co-transmission. Recently, we and others have studied neurons that project to the lateral habenula and release both gamma-aminobutyric acid (GABA) and glutamate, in some cases by packaging both transmitters in the same synaptic vesicles. Here, we discuss the main challenges with current electrophysiological approaches to studying the mechanisms of glutamate/GABA co-release, a novel statistical analysis that can identify co-packaging of neurotransmitters versus release from separate vesicle, and the implications of glutamate/GABA co-release for synapse function and plasticity.

Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons Inhibits Pyramidal Cells.

We studied how histamine and GABA release from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influence circuit processing. We optostimulated histamine/GABA from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDC axons). Whole-cell recordings from PFC neurons in layer 2/3 of prelimbic, anterior cingulate, and infralimbic regions were used to monitor excitability before and after optostimulated histamine/GABA release in male and female mice. We found that histamine-GABA release influences the PFC through actions on distinct neuronal types: the histamine stimulates fast-spiking interneurons; and the released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast-spiking nonaccommodating interneurons, histamine released from TMNHDC axons induced additive gain changes, which were blocked by histamine H1 and H2 receptor antagonists. The excitability of other fast-spiking interneurons in the PFC was not altered. In contrast, the GABA released from TMNHDC axons predominantly produced divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. This inhibitory effect on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAA receptor antagonists. Across the adult life span (from 3 to 18 months of age), the GABA released from TMNHDC axons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals who maintain cognitive performance into later life, the increases in TMNHDC GABA modulation of PyrNs during aging could enhance information processing and be an adaptive mechanism to buttress cognition.SIGNIFICANCE STATEMENT The hypothalamus controls arousal state by releasing chemical neurotransmitters throughout the brain to modulate neuronal excitability. Evidence is emerging that the release of multiple types of neurotransmitters may have opposing actions on neuronal populations in key cortical regions. This study demonstrates for the first time that the neurotransmitters histamine and GABA are released in the prefrontal cortex from axons originating from the tuberomammillary nucleus of the hypothalamus. This work demonstrates how hypothalamic modulation of neuronal excitability is maintained throughout adult life, highlighting an unexpected aspect of the aging process that may help maintain cognitive abilities.

Dopamine and the Causes, Prevention, and Advanced Treatments of Parkinson’s Disease.

Parkinson's disease (PD) is a neurodegenerative disorder with a wide range of motor and non-motor symptoms. Despite optimal medical management, PD still results in a high disability rate and secondary complications, and many patients lead a sedentary lifestyle, which in turn is also associated with a higher co-morbidity and mortality. Dopamine is a type of monoamine neurotransmitter. It is made in your brain and acts as a chemical messenger, communicating messages between nerve cells in your brain and the rest of your body. Dopamine is what motivates us to do something. Dopamine is a large factor in many of our day-to-day actions: it decides our mood, what we remember, and even how we move and act. This Dopamine and PD study is anticipated to inform those with PD of treatments that work better than others. Strong elements of this research paper include treatments such as MR-Guided focused Ultrasound, Gene Therapy, Park-in-Shape, and the rise of a PD Vaccine. This research paper's secondary goal is to inform those looking to avoid PD or who already have PD and wish to avoid the symptoms on how to avoid the symptoms of the disease. This Dopamine and PD study aims to explain what dopamine is, how it works, how it affects the body, and the effects of unhealthy levels of dopamine.

Emulating Excitatory and Inhibitory Functions in Artificial Synaptic Devices

Synaptic signals are controlled by neurotransmitters. The synaptic signals can be excited or inhibited depending on the types of neurotransmitters. The demonstration of the balancing between excitatory and inhibitory signals has important implications for the complex and efficient computing of the nervous system. Emulating the excitatory-inhibitory balancing behaviors of the nervous system is one way to establish neuromorphic computing. In this study, we demonstrate artificial synapses using PEDOT:PSS channel and neurotransmitter solutions to emulate the excitatory-inhibitory balancing behaviors. The devices show excitatory and inhibitory postsynaptic characteristics using the neurotransmitter solutions. Also, using the interaction between excitatory and inhibitory synaptic responses, the devices emulate the excitatory-inhibitory balancing behaviors of the nervous system. The devices exhibit multifunctional characteristics similar to the biological synapses, resulting in their potential for use in neuromorphic devices.

Distinct cell populations of ventral tegmental area process motivated behavior

It is well known that dopamine transmission from the ventral tegmental area (VTA) modulates motivated behavior and reinforcement learning. Although dopaminergic neurons are the major type of VTA neurons, recent studies show that a significant proportion of the VTA contains GABAergic and type 2 vesicular glutamate transporter (VGLUT2)-positive neurons. The non-dopaminergic neurons are also critically involved in regulating motivated behaviors. Some VTA neurons appear to co-release two different types of neurotransmitters. They are VGLUT2-DA neurons, VGLUT2-GABA neurons and GABA-DA neurons. These co-releasing neurons show distinct features compared to the neurons that release a single neurotransmitter. Here, we review how VTA cell populations wire to the other brain regions and how these projections differentially contribute to motivated behavior through the distinct molecular mechanism. We summarize the activities, projections and functions of VTA neurons concerning motivated behavior. This review article discriminates VTA cell populations related to the motivated behavior based on the neurotransmitters they release and extends the classical view of the dopamine-mediated reward system.

A Pilot Study on Plasma and Urine Neurotransmitter Levels in Children with Tic Disorders.

Background: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and/or vocal tics that commonly affect children’s physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and serotonergic neurotransmitters. The purpose of this study was to preliminarily investigate the differences in the three types of neurotransmitters in plasma and urine between children with TD and healthy children. Methods: We collected 94 samples of plasma and 69 samples of urine from 3–12-year-old Chinese Han children with TD before treatment. The plasma and urine of the same number of healthy Chinese Han children, matched for age and sex, participating in a physical examination, were collected. Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the three types of neurotransmitters in the above samples. Results: The plasma levels of norepinephrine, glutamic acid, and γ-aminobutyric acid, and the urine levels of normetanephrine and 5-hydroxyindoleacetic acid were higher in the TD children than in healthy children. The area under the curve (AUC) values of the above neurotransmitters in plasma and urine analyzed by receiver operating characteristic curve analysis were all higher than 0.6, with significant differences. Among them, the combined AUC of dopamine, norepinephrine, normetanephrine, glutamic acid, and γ-aminobutyric acid in the 8–12-year-old subgroup was 0.930, and the sensitivity and specificity for TD were 0.821 and 0.974, respectively (p = 0.000). Conclusions: There are differences in plasma and urine neurotransmitters between TD children and healthy children, which lays a foundation for further research on the pathogenesis of TD.

Abstract 633: Delineating tumor-neural communication in brain metastasis with spatiotemporal transcriptomic analysis and multi-cellular crosstalk modeling

Abstract Brain metastases are diagnosed in 20-40% of all cancer patients. Despite the advancements in neurosurgery, radiotherapy, and chemotherapy, one-year survival of metastatic brain tumor patients still within a single digit such that brain metastases constitute about 20% of annual cancer deaths. These facts clearly indicate a critical need for better understanding of mechanisms that promote the growth of brain metastases. Emerging data, including ours, indicate that different types of metastatic cancer cells leverage dissimilar sets of neurotransmitters to favor their outgrowth in the brain. However, there are over sixty types of neurotransmitters in the brain being synthesized and released by various types of neural cells, we need a systemic investigation of how they mediate the pathogenesis of brain metastases in concert. Since neurotransmitters, gliotransmitters, neurotrophic factors, and neural cytokines, called neuroactive substances, are the most abundant and key intercellular communication signals in the brain, we hypothesize that tumor cells leverage these neuroactive substances to assimilate into neural circuitry via communicating with neural cells including neurons, astrocytes, microglia, oligodendrocyte, and others, in promoting the vicious circle of tumor-neural crosstalk during brain metastasis development. By performing spatial transcriptomics analysis on mouse brain sections bearing metastatic tumors, we found that tumor lesions at different locations and even tumor-surrounding areas in the brain regions could be differentiated into different cellular clusters based on gene transcriptomic expressions. We further predicted several paracrine and autocrine signaling between and within tumors as well as tumor-surrounding neural niches in different tumor locations (e.g., centers or edges), of different tumor sizes, and at various tumor development stages, using our Cell-Cell Communication Explorer (CCC-Explorer) modeling software. Functional experiments were conducted to demonstrate that cell type-specific depletion of the secreted NSs deactivated the activities of corresponding receptors and downstream signaling in co-cultured metastatic brain tumor cells. Characterizing spatiotemporal tumor-neural crosstalk in the brain metastatic niche would provide a new strategy in the development of novel and effective therapeutics of brain metastases. Citation Format: Xin Wang, Ying Zhu, Jianting Sheng, Hong Zhao, Stephen Wong. Delineating tumor-neural communication in brain metastasis with spatiotemporal transcriptomic analysis and multi-cellular crosstalk modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 633.

Potential benefits of exogenous neurotransmitters in alleviating transport stress in koi carp, Cyprinus carpio

The transport of live fish is an important process in the ornamental fish trade. As such, reducing transport stress plays a vital role in improving fish survival and minimizing economic losses. The objective of this study was to assess the efficacy of exogenous neurotransmitters in alleviating transport stress in koi carp, Cyprinus carpio. First, fish were subjected to simulated transport, and samples were collected at 0, 4, 6, 12, 24, and 48 h for the determination of water quality parameters and serum indices. The results indicated that the pH of the water decreased and ammonium nitrogen (NH4-N) was enhanced with the increase of transport time. The most significant changes in stress-related indices were observed at 4 h after transport, and thus the subsequent transport experiments were scheduled for 4 h. Three types of exogenous neurotransmitters were added to the water, and fish were transported for 4 h to determine the efficacy of the neurotransmitters. Gamma-aminobutyric acid (GABA) increased the pH, and decreased the NH4-N content of the water. The concentrations of serum adrenaline, cortisol, and glucose were decreased by GABA supplementation. Guanidine acetic acid (GAA) increased the pH of the water, and decreased the concentrations of serum adrenaline and cortisol. The addition of 5-hydroxytryptamine (5-HT) lowered the NH4-N level of the water, and decreased the concentrations of serum adrenaline and cortisol in the fish. In conclusion, the addition of exogenous neurotransmitters to transport water may help to alleviate transport stress by improving water quality and depressing the enhancement of stress-related hormones.