Role In Neurotransmission Research Articles

Role of Neurotransmitters (Biomediators) in Plant Responses to Stress

Role of Neurotransmitters (Biomediators) in Plant Responses to Stress

The activation of inflammatory responses in the brain is potentiated by over-expressing acetylcholinesterase in myeloid lineage of transgenic mice.

Acetylcholinesterase (AChE) has functions in neuroinflammation, beyond its classical role in neurotransmission. Understanding the role of AChE in neuroinflammation is of great significance, as it highlights the potential therapeutic targets for the treatment of neurodegenerative diseases. In an invitro study, the expression of AChE was up-regulated in lipopolysaccharide (LPS)-induced microglia/macrophage and contrarily potentiated the inflammatory responses via disturbing the cholinergic anti-inflammatory pathway (CAP). However, the regulation of AChE in neuroinflammation has not been revealed invivo yet. Here, we aim to uncover the inflammatory roles of microglial AChE in LPS-induced neuroinflammation by using the conditional AChE over-expression mouse model. AChE was specifically over-expressed in the myeloid cell linkage of mouse by applying CRISPR/cas9 combined with Cre-LoxP system. LPS was intraperitoneally injected into the mice to induce inflammation. The results showed that the inflammation, induced by LPS, was aggravated in the brain of transgenic mice having over-expression of AChE in microglia. The expressions of pro-inflammatory cytokines were robustly up-regulated in the brains of LPS-treated transgenic mice, as compared to the LPS-treated wildtypes. In parallel, the activations of microglia and astrocytes in hippocampus were enhanced significantly in AChE transgenic mice. Transcriptomics analysis further confirmed the severer inflammation in the transgenic mice than the wildtype after LPS administration. These findings shed light on the regulation of microglial AChE in neuroinflammation invivo for the first time, presenting another angle to understand the role of AChE in neurodegenerative diseases.

Pharmacology and toxicology of Acetylcholinesterase: mechanisms, therapeutic potential, and environmental impact

Acetylcholinesterase (AChE) is a critical enzyme in the nervous system, responsible for terminating synaptic transmission by hydrolyzing acetylcholine. Due to its key role in neurotransmission, AChE and its inhibitors have become significant in treating neurological disorders such as Alzheimer’s, Parkinson’s, and Myasthenia Gravis. However, AChE inhibitors are also widely used in agriculture, posing potential environmental hazards as pesticides. This review provides a detailed analysis of the pharmacological role, therapeutic applications, and toxicological implications of AChE inhibitors. While these compounds offer therapeutic benefits, their environmental persistence and non-target toxicity raise ecological concerns. Balancing the dual impact of AChE inhibitors is vital to maximizing their benefits while minimizing risks.

White matter integrity and motor function: a link between cerebral myelination and longitudinal changes in gait speed in aging.

Gait speed is a robust health biomarker in older adults, correlating with the risk of physical and cognitive impairments, including dementia. Myelination plays a crucial role in neurotransmission and consequently affects various functions, yet the connection between myelination and motor functions such as gait speed is not well understood. Understanding this link could offer insights into diagnosing and treating neurodegenerative diseases that impair mobility. This study analyzed 437 longitudinal observations from 138 cognitively unimpaired adults, aged 22 to 94years, to investigate the relationship between myelin content and changes in gait speed over an average of 6.42years. Myelin content was quantified using a novel multicomponent magnetic resonance relaxometry method, and both usual and rapid gait speeds (UGS, RGS) were measured following standard protocols. Adjusting for covariates, we found a significant fixed effect of myelin content on UGS and RGS. Longitudinally, lower myelin content was linked to a greater decline in UGS, particularly in brain regions associated with motor planning. These results suggest that changes in UGS may serve as a reliable marker of neurodegeneration, particularly in cognitively unimpaired adults. Interestingly, the relationship between myelin content and changes in RGS was only observed in a limited number of brain regions, although the reason for such local susceptibility remains unknown. These findings enhance our understanding of the critical role of myelination in gait performance in unimpaired adults and provide evidence of the interconnection between myelin content and motor functionimpairment.

Neural mechanisms of mutualistic fish cleaning behaviour: a study in the wild.

One crucial interaction for the health of fish communities in coral reefs is performed by cleaner fish by removing ectoparasites from the body of other fish, so-called clients. Studying the underlying mechanisms of this behaviour is essential to understanding how species react to social stimuli and defining the drivers of mutualistic social behaviour. Here, we pinpoint the neural molecular mechanisms in the cleaning behaviour of Labroides dimidiatus in the wild through an in situ interaction experiment at a coral reef in New Caledonia. Five cleaners and clients (Abudefduf saxatilis) were placed into underwater aquaria to interact, while five were not presented with a client. The brain transcriptomes revealed 233 differentially expressed genes in cleaners that were interacting with a client. Among these genes, grin2d, npy, slc6a3 and immediate early genes (IEGs; fosb and fosl1) were related to learning and memory, glutamate and dopamine pathways, which confirm molecular pathways observed in laboratory studies. However, a new potential mechanism was found with npy (neuropeptide Y) as a driver of feeding behaviour. These results show the role of neurotransmitters and IEGs in mutualistic social behaviour, unveiling the mechanism behind the feeding stimulus that leads the cleaner fish to establish mutualistic interactions in coral reefs.

The regulatory roles of a plant neurotransmitter, acetylcholine, on growth, PSII photochemistry and antioxidant systems in wheat exposed to cadmium and/or mercury stress

Heavy metals increase in nature due to anthropogenic activities and negatively impact the growth, progress, and efficiency of plants. Among the toxic metal pollutants that can cause dangerous effects when accumulated by plants, mercury (Hg) and cadmium (Cd) were investigated in this study. These metals typically inhibit important enzymes and halt their functioning, thereby adversely affecting the capability of plants to achieve photosynthesis, respiration, and produce quality crops. Acetylcholine (ACh) serves as a potent neurotransmitter present in both primitive and advanced plant species. Its significant involvement in diverse metabolic processes, particularly in regulating growth and adaptation to stress, needs to be further elucidated. For this aim, effects of acetylcholine (ACh1, 10 μM; ACh2, 100 μM) were survey in Triticum aestivum under Hg and/or Cd stress (Hg, 50 μM; Cd, 100 μM). Wheat seedlings exhibited a growth retardation of about 24% under Hg or Cd stress. Combined stress conditions (Cd + Hg) resulted in a decrease in RWC by approximately 16%. Two different doses of ACh treatment to stressed plants positively affected growth parameters and regulated the water relations. Gas exchange was limited in stress groups, and the photochemical quantum competency of PSII (Fv/Fm) was suppressed. Cd + ACh1 and Cd + ACh2 treatments resulted in approximately 2-fold and 1.5-fold improvement in stomatal conductance and carbon assimilation rate, respectively. Similarly, improvement was observed with ACh treatments in wheat seedlings under Hg stress. Under Cd and/or Hg stress, high levels of H2O2 accumulated and lipid peroxidation occurred. According to our results, ACh treatment upon Cd and Hg stresses improved the activities of SOD, POX, and APX, thereby reducing oxidative damage. In conclusion, ACh treatment was found to ensure stress tolerance and limit the adverse effects caused by heavy metals.

Differential functions of phosphatidylinositol 4-kinases in neurotransmission and synaptic development.

Phosphoinositides, such as PI(4,5)P2, are known to function as structural components of membranes, signalling molecules, markers of membrane identity, mediators of protein recruitment and regulators of neurotransmission and synaptic development. Phosphatidylinositol 4-kinases (PI4Ks) synthesize PI4P, which are precursors for PI(4,5)P2, but may also have independent functions. The roles of PI4Ks in neurotransmission and synaptic development have not been studied in detail. Previous studies on PI4KII and PI4KIIIβ at the Drosophila larval neuromuscular junction have suggested that PI4KII and PI4KIIIβ enzymes may serve redundant roles, where single PI4K mutants yielded mild or no synaptic phenotypes. However, the precise synaptic functions (neurotransmission and synaptic growth) of these PI4Ks have not been thoroughly studied. Here, we used PI4KII and PI4KIIIβ null mutants and presynaptic-specific knockdowns of these PI4Ks to investigate their roles in neurotransmission and synaptic growth. We found that PI4KII and PI4KIIIβ appear to have non-overlapping functions. Specifically, glial PI4KII functions to restrain synaptic growth, whereas presynaptic PI4KIIIβ promotes synaptic growth. Furthermore, loss of PI4KIIIβ or presynaptic PI4KII impairs neurotransmission. The data presented in this study uncover new roles for PI4K enzymes in neurotransmission and synaptic growth.

Mechanistic Concepts of Multifaceted Roles of Neurotransmitters Like Signalling Molecules in Plant Responses to Biotic Stress

Mechanistic Concepts of Multifaceted Roles of Neurotransmitters Like Signalling Molecules in Plant Responses to Biotic Stress

Assessing the Impact of IL-6 and Serotonin on Pain and Symptomatology in Fibromyalgia: An Exploratory Clinical Study.

Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome characterized by widespread pain and a variety of other symptoms, including fatigue, cognitive dysfunction, and sleep disturbances. Recent research has highlighted the potential role of pro-inflammatory cytokines and neurotransmitters in the pathophysiology of FM. This study aimed to investigate the relationship between serum levels of interleukin-6 (IL-6) and serotonin with the clinical parameters observed in patients with fibromyalgia. Additionally, it sought to analyze the similarities and differences among the different groups classified by symptom severity. This cross-sectional study included 26 female patients aged 20-70 diagnosed with FM according to the American College of Rheumatology (ACR) 2016 criteria and 14 healthy controls (HCs). Serum levels of IL-6 and serotonin were measured using electrochemiluminescence and high-performance liquid chromatography (HPLC), respectively. FM patients exhibited significantly higher pain scores (VAS), anxiety, and depression levels compared to HCs. FIQ-R scores were significantly elevated in FM patients, with stratification showing 3.8% mild, 65.4% moderate, 23.1% severe, and 7.7% very severe cases. While no significant difference in IL-6 levels was observed between the FM patients and HCs, a trend towards increased IL-6 levels in patients with higher FIQ-R scores was noted. Serum serotonin levels were significantly lower in the FM patients than in the HCs, with moderate patients having lower levels than those classified as severe and very severe. The study underscores the potential role of IL-6 and serotonin in the pathophysiology of FM, suggesting that these biomarkers could be relevant in assessing the severity and impact of FM. Further research is needed to elucidate these relationships and their implications for developing personalized treatment strategies.

Supraspinal glycinergic neurotransmission in pain: A scoping review of current literature.

The neurotransmitter glycine is an agonist at the strychnine-sensitive glycine receptors. In addition, it has recently been discovered to act at two new receptors, the excitatory glycine receptor and metabotropic glycine receptor. Glycine's neurotransmitter roles have been most extensively investigated in the spinal cord, where it is known to play essential roles in pain, itch, and motor function. In contrast, less is known about supraspinal glycinergic functions, and their contributions to pain circuits are largely unrecognized. As glycinergic neurons are absent from cortical regions, a clearer understanding of how supraspinal glycine modulates pain could reveal new pharmacological targets. This review aims to synthesize the published research on glycine's role in the adult brain, highlighting regions where glycine signaling may modulate pain responses. This was achieved through a scoping review methodology identifying several key regions of supraspinal pain circuitry where glycine signaling is involved. Therefore, this review unveils critical research gaps for supraspinal glycine's potential roles in pain and pain-associated responses, encouraging researchers to consider glycinergic neurotransmission more widely when investigating neural mechanisms of pain.

Role of Biosynthesis and Catabolism of Neurotransmitters in Drug Discovery for Anxiety and Depression.

The purpose of this review is to correlate the probable causes of anxiety disorders with the imbalance of neurotransmitters in the brain and also highlight the drugs for these mental disorders that have been discovered based on the biosynthesis and catabolism of these brain chemicals. Peer-reviewed journal's articles, news and books published in English between 1997 and 2023 describing the role of neurotransmitters in anxiety disorders were searched in Google Scholar, Research Gate and PubMed databases. The contents were carefully analyzed by the authors and understood and compiled to build a concise perspective on the role of biosynthesis and catabolism of neurotransmitters in anxiety and depression. Anxiety disorders are reported to be common patterns of psychological symptoms that impact multiple areas of life. Anxiety and depression are prevalent worldwide and are significantly contributing towards the global health burden. Genetic determinants are believed to play an important role in these disorders. According to modern medicine, one of the most important aspects that is known to be crucial for these disorders is the imbalance of neurotransmitters in the brain. The biosynthesis and catabolism of neurotransmitters have been extensively targeted for innovative drug discovery approaches at various steps that have led to the discovery of many drugs for these psychological disorders. The biosynthetic and catabolic reaction cycles of neurotransmitters and the discovery of drugs based on these hypotheses are discussed. To the best of the authors' knowledge, this review compiles already known descriptive knowledge on "relation of neurotransmitter imbalance with anxiety disorders" in a precise way that will provide readers with an overview of the vast literature.

An Expanded Narrative Review of Neurotransmitters on Alzheimer's Disease: The Role of Therapeutic Interventions on Neurotransmission.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for the pathogenesis of the disease. The accumulation of Aβ plaques and tau affect the balance in chemical neurotransmitters in the brain. Thus, the current review examined the role of neurotransmitters in the pathogenesis of Alzheimer's disease and discusses the alterations in the neurochemical activity and cross talk with their receptors and transporters. In the presence of Aβ plaques and neurofibrillary tangles, changes may occur in the expression of neuronal receptors which in turn triggers excessive release of glutamate into the synaptic cleft contributing to cell death and neuronal damage. The GABAergic system may also be affected by AD pathology in a similar way. In addition, decreased receptors in the cholinergic system and dysfunction in the dopamine neurotransmission of AD pathology may also contribute to the damage to cognitive function. Moreover, the presence of deficiencies in noradrenergic neurons within the locus coeruleus in AD suggests that noradrenergic stimulation could be useful in addressing its pathophysiology. The regulation of melatonin, known for its effectiveness in enhancing cognitive function and preventing Aβ accumulation, along with the involvement of the serotonergic system and histaminergic system in cognition and memory, becomes remarkable for promoting neurotransmission in AD. Additionally, nitric oxide and adenosine-based therapeutic approaches play a protective role in AD by preventing neuroinflammation. Overall, neurotransmitter-based therapeutic strategies emerge as pivotal for addressing neurotransmitter homeostasis and neurotransmission in the context of AD. This review discussed the potential for neurotransmitter-based drugs to be effective in slowing and correcting the neurodegenerative processes in AD by targeting the neurochemical imbalance in the brain. Therefore, neurotransmitter-based drugs could serve as a future therapeutic strategy to tackle AD.

Role of Neurotransmitters in Steady State Hematopoiesis, Aging, and Leukemia.

Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.

Mood Changes in Premenstrual Syndrome seen from Hormonal Changes in the Pituitary Gland

Introduction: The pituitary gland plays a role in the production of the hormones FSH and LH, which influence development follicles And process ovulation. In addition, the pituitary gland indirectly plays a role in regulating the production of serotonin, a neurotransmitter role in arrange atmosphere heart. This research aims to find out about the role of the pituitary gland in mood changes during the premenstrual period. Methodology: This research uses a literature study method by examining existing data. Results: Research results show that change atmosphere liver in the premenstrual phase can caused by change hormonal, like decline production serotonin consequence decreasing rate hormone estrogen and progesterone, which influence mood and emotions. Discussion: The pituitary gland has a role in influencing the ovulation process in the premenstrual phase and also regulates serotonin production which causes an imbalance in the hormones produced by the ovaries, namely estrogen and progesterone, resulting in mood swings.

Revealing molecular determinants governing mambalgin-3 pharmacology at acid-sensing ion channel 1 variants

Acid-sensing ion channels (ASICs) are trimeric proton-gated cation channels that play a role in neurotransmission and pain sensation. The snake venom-derived peptides, mambalgins, exhibit potent analgesic effects in rodents by inhibiting central ASIC1a and peripheral ASIC1b. Despite their distinct species- and subtype-dependent pharmacology, previous structure-function studies have focussed on the mambalgin interaction with ASIC1a. Currently, the specific channel residues responsible for this pharmacological profile, and the mambalgin pharmacophore at ASIC1b remain unknown. Here we identify non-conserved residues at the ASIC1 subunit interface that drive differences in the mambalgin pharmacology from rat ASIC1a to ASIC1b, some of which likely do not make peptide binding interactions. Additionally, an amino acid variation below the core binding site explains potency differences between rat and human ASIC1. Two regions within the palm domain, which contribute to subtype-dependent effects for mambalgins, play key roles in ASIC gating, consistent with subtype-specific differences in the peptides mechanism. Lastly, there is a shared primary mambalgin pharmacophore for ASIC1a and ASIC1b activity, with certain peripheral peptide residues showing variant-specific significance for potency. Through our broad mutagenesis studies across various species and subtype variants, we gain a more comprehensive understanding of the pharmacophore and the intricate molecular interactions that underlie ligand specificity. These insights pave the way for the development of more potent and targeted peptide analogues required to advance our understating of human ASIC1 function and its role in disease.

The Lack of Synapsin Alters Presynaptic Plasticity at Hippocampal Mossy Fibers in Male Mice.

Synapsins are highly abundant presynaptic proteins that play a crucial role in neurotransmission and plasticity via the clustering of synaptic vesicles. The synapsin III isoform is usually downregulated after development, but in hippocampal mossy fiber boutons, it persists in adulthood. Mossy fiber boutons express presynaptic forms of short- and long-term plasticity, which are thought to underlie different forms of learning. Previous research on synapsins at this synapse focused on synapsin isoforms I and II. Thus, a complete picture regarding the role of synapsins in mossy fiber plasticity is still missing. Here, we investigated presynaptic plasticity at hippocampal mossy fiber boutons by combining electrophysiological field recordings and transmission electron microscopy in a mouse model lacking all synapsin isoforms. We found decreased short-term plasticity, i.e., decreased facilitation and post-tetanic potentiation, but increased long-term potentiation in male synapsin triple knock-out (KO) mice. At the ultrastructural level, we observed more dispersed vesicles and a higher density of active zones in mossy fiber boutons from KO animals. Our results indicate that all synapsin isoforms are required for fine regulation of short- and long-term presynaptic plasticity at the mossy fiber synapse.

General and anxiety-linked influences of acute serotonin reuptake inhibition on neural responses associated with attended visceral sensation

Ordinary sensations from inside the body are important causes and consequences of our affective states and behaviour, yet the roles of neurotransmitters in interoceptive processing have been unclear. With a within-subjects design, this experiment tested the impacts of acute increases of endogenous extracellular serotonin on the neural processing of attended internal sensations and the links of these effects to anxiety using a selective serotonin reuptake inhibitor (SSRI) (20 mg citalopram) and a placebo. Twenty-one healthy volunteers (fourteen female, mean age 23.9) completed the Visceral Interoceptive Attention (VIA) task while undergoing functional magnetic resonance imaging (fMRI) with each treatment. The VIA task required focused attention on the heart, stomach, or visual sensation. The relative neural interoceptive responses to heart sensation [heart minus visual attention] (heart-IR) and stomach sensation [stomach minus visual attention] (stomach-IR) were compared between treatments. Visual attention subtraction controlled for the general effects of citalopram on sensory processing. Citalopram was associated with lower interoceptive processing in viscerosensory (the stomach-IR of bilateral posterior insular cortex) and integrative/affective (the stomach-IR and heart-IR of bilateral amygdala) components of interoceptive neural pathways. In anterior insular cortex, citalopram reductions of heart-IR depended on anxiety levels, removing a previously known association between anxiety and the region’s response to attended heart sensation observed with placebo. Preliminary post hoc analysis indicated that citalopram effects on the stomach-IR of the amygdalae corresponded to acute anxiety changes. This direct evidence of general and anxiety-linked serotonergic influence on neural interoceptive processes advances our understanding of interoception, its regulation, and anxiety.

The Regulatory Role of Sleep Hormones, Neurotransmitters, and Gene Expression in Rapid Eye Movement Sleep

The Regulatory Role of Sleep Hormones, Neurotransmitters, and Gene Expression in Rapid Eye Movement Sleep

Phospholipid Scramblase 1 Controls Efficient Neurotransmission and Synaptic Vesicle Retrieval at Cerebellar Synapses.

Phospholipids (PLs) are asymmetrically distributed at the plasma membrane. This asymmetric lipid distribution is transiently altered during calcium-regulated exocytosis, but the impact of this transient remodeling on presynaptic function is currently unknown. As phospholipid scramblase 1 (PLSCR1) randomizes PL distribution between the two leaflets of the plasma membrane in response to calcium activation, we set out to determine its role in neurotransmission. We report here that PLSCR1 is expressed in cerebellar granule cells (GrCs) and that PLSCR1-dependent phosphatidylserine egress occurred at synapses in response to neuron stimulation. Synaptic transmission is impaired at GrC Plscr1 -/- synapses, and both PS egress and synaptic vesicle (SV) endocytosis are inhibited in Plscr1 -/- cultured neurons from male and female mice, demonstrating that PLSCR1 controls PL asymmetry remodeling and SV retrieval following neurotransmitter release. Altogether, our data reveal a novel key role for PLSCR1 in SV recycling and provide the first evidence that PL scrambling at the plasma membrane is a prerequisite for optimal presynaptic performance.

Unraveling emotional regulation through multimodal neuroimaging techniques

Neuroimaging techniques have significantly advanced our understanding of emotional regulation by elucidating the neural mechanisms involved. This review synthesizes findings across multiple modalities—functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), Magnetoencephalography (MEG), Positron Emission Tomography (PET), and Magnetic Resonance Spectroscopy (MRS)—to highlight key insights into emotional processing. The prefrontal cortex (PFC), amygdala, hippocampus, and insula emerge as critical brain regions in regulating emotions. fMRI studies demonstrate increased PFC activity and decreased amygdala responses during effective emotion regulation, indicating top-down control mechanisms. EEG and MEG provide insights into the temporal dynamics of emotional responses, capturing rapid changes in neural activity during emotional tasks. PET and MRS studies reveal the neurochemical basis of emotional regulation, emphasizing the roles of neurotransmitters like serotonin and dopamine. Integration of multimodal approaches, such as fMRI-EEG and fMRI-PET, enhances our understanding by combining spatial, temporal, and neurochemical specificity. Challenges include methodological limitations and the need for diverse participant samples to improve generalizability. Future research should focus on improving spatial and temporal resolution, adopting longitudinal and ecologically valid designs, and fostering interdisciplinary collaborations. These advancements hold promise for developing personalized interventions and treatments for emotional disorders by leveraging neuroimaging biomarkers and understanding the neural underpinnings of emotional regulation.