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Frontiers in Immunology 2021Neurological and immunological signals constitute an extensive regulatory network in our body that maintains physiology and homeostasis. The cholinergic system plays a... (Review)
Review
Neurological and immunological signals constitute an extensive regulatory network in our body that maintains physiology and homeostasis. The cholinergic system plays a significant role in neuroimmune communication, transmitting information regarding the peripheral immune status to the central nervous system (CNS) and vice versa. The cholinergic system includes the neurotransmitter\ molecule, acetylcholine (ACh), cholinergic receptors (AChRs), choline acetyltransferase (ChAT) enzyme, and acetylcholinesterase (AChE) enzyme. These molecules are involved in regulating immune response and playing a crucial role in maintaining homeostasis. Most innate and adaptive immune cells respond to neuronal inputs by releasing or expressing these molecules on their surfaces. Dysregulation of this neuroimmune communication may lead to several inflammatory and autoimmune diseases. Several agonists, antagonists, and inhibitors have been developed to target the cholinergic system to control inflammation in different tissues. This review discusses how various molecules of the neuronal and non-neuronal cholinergic system (NNCS) interact with the immune cells. What are the agonists and antagonists that alter the cholinergic system, and how are these molecules modulate inflammation and immunity. Understanding the various functions of pharmacological molecules could help in designing better strategies to control inflammation and autoimmunity.
Topics: Animals; Autoimmunity; Cholinergic Agents; Humans; Inflammation; Mice; Neurons; Receptors, Cholinergic; Signal Transduction
PubMed: 33936095
DOI: 10.3389/fimmu.2021.660342 -
Neuron Nov 2022Cholinergic neurons in the medial septum (MS) constitute a major source of cholinergic input to the forebrain and modulate diverse functions, including sensory...
Cholinergic neurons in the medial septum (MS) constitute a major source of cholinergic input to the forebrain and modulate diverse functions, including sensory processing, memory, and attention. Most studies to date have treated cholinergic neurons as a single population; as such, the organizational principles underling their functional diversity remain unknown. Here, we identified two subsets (D28K versus D28K) of cholinergic neurons that are topographically segregated in mice, Macaca fascicularis, and humans. These cholinergic subpopulations possess unique electrophysiological signatures, express mutually exclusive marker genes (kcnh1 and aifm3 versus cacna1h and gga3), and make differential connections with physiologically distinct neuronal classes in the hippocampus to form two structurally defined and functionally distinct circuits. Gain- and loss-of-function studies on these circuits revealed their differential roles in modulation of anxiety-like behavior and spatial memory. These results provide a molecular and circuitry-based theory for how cholinergic neurons contribute to their diverse behavioral functions.
Topics: Humans; Mice; Animals; Cholinergic Neurons; Cholinergic Agents; Prosencephalon; Hippocampus
PubMed: 36130594
DOI: 10.1016/j.neuron.2022.08.025 -
PloS One 2013Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the... (Review)
Review
Mushroom-forming fungi produce a wide array of toxic alkaloids. However, evolutionary analyses aimed at exploring the evolution of muscarine, a toxin that stimulates the parasympathetic nervous system, and psilocybin, a hallucinogen, have never been performed. The known taxonomic distribution of muscarine within the Inocybaceae is limited, based only on assays of species from temperate regions of the northern hemisphere. Here, we present a review of muscarine and psilocybin assays performed on species of Inocybaceae during the last fifty years. To supplement these results, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine whether muscarine was present in 30 new samples of Inocybaceae, the majority of which have not been previously assayed or that originated from either the tropics or temperate regions of the southern hemisphere. Our main objective is to test the hypothesis that the presence of muscarine is a shared ancestral feature of the Inocybaceae. In addition, we also test whether species of Inocyabceae that produce psilocybin are monophyletic. Our findings suggest otherwise. Muscarine has evolved independently on several occasions, together with several losses. We also detect at least two independent transitions of muscarine-free lineages to psilocybin-producing states. Although not ancestral for the family as a whole, muscarine is a shared derived trait for an inclusive clade containing three of the seven major lineages of Inocybaceae (the Inocybe, Nothocybe, and Pseudosperma clades), the common ancestor of which may have evolved ca. 60 million years ago. Thus, muscarine represents a conserved trait followed by several recent losses. Transitions to psilocybin from muscarine-producing ancestors occurred more recently between 10-20 million years ago after muscarine loss in two separate lineages. Statistical analyses firmly reject a single origin of muscarine-producing taxa.
Topics: Agaricales; Animals; Evolution, Molecular; Fruiting Bodies, Fungal; Genetic Speciation; Humans; Muscarine; Phylogeny; Psilocybin; Sequence Analysis, DNA
PubMed: 23717644
DOI: 10.1371/journal.pone.0064646 -
Molecules (Basel, Switzerland) Apr 2021Epilepsy is a common brain disorder characterized by recurrent epileptic seizures with neuronal hyperexcitability. Apart from the classical imbalance between excitatory... (Review)
Review
Epilepsy is a common brain disorder characterized by recurrent epileptic seizures with neuronal hyperexcitability. Apart from the classical imbalance between excitatory glutamatergic transmission and inhibitory γ-aminobutyric acidergic transmission, cumulative evidence suggest that cholinergic signaling is crucially involved in the modulation of neural excitability and epilepsy. In this review, we briefly describe the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability. Then, we summarize the findings from experimental and clinical research on the role of cholinergic signaling in epilepsy. Furthermore, we provide some perspectives on future investigation to reveal the precise role of the cholinergic system in epilepsy.
Topics: Animals; Cholinergic Agents; Epilepsy; Humans; Receptors, Nicotinic
PubMed: 33924731
DOI: 10.3390/molecules26082258 -
Nature Neuroscience Dec 2022Variation in an animal's behavioral state is linked to fluctuations in brain activity and cognitive ability. In the neocortex, state-dependent circuit dynamics may...
Variation in an animal's behavioral state is linked to fluctuations in brain activity and cognitive ability. In the neocortex, state-dependent circuit dynamics may reflect neuromodulatory influences such as that of acetylcholine (ACh). Although early literature suggested that ACh exerts broad, homogeneous control over cortical function, recent evidence indicates potential anatomical and functional segregation of cholinergic signaling. In addition, it is unclear whether states as defined by different behavioral markers reflect heterogeneous cholinergic and cortical network activity. Here, we perform simultaneous, dual-color mesoscopic imaging of both ACh and calcium across the neocortex of awake mice to investigate their relationships with behavioral variables. We find that higher arousal, categorized by different motor behaviors, is associated with spatiotemporally dynamic patterns of cholinergic modulation and enhanced large-scale network correlations. Overall, our findings demonstrate that ACh provides a highly dynamic and spatially heterogeneous signal that links fluctuations in behavior to functional reorganization of cortical networks.
Topics: Animals; Mice; Neocortex; Acetylcholine; Arousal; Calcium; Cholinergic Agents
PubMed: 36443609
DOI: 10.1038/s41593-022-01202-6 -
Molecules (Basel, Switzerland) Sep 2022In recent years, an impressive number of research studies have been conducted to improve the understanding of the structure and function of the cholinergic system, and...
In recent years, an impressive number of research studies have been conducted to improve the understanding of the structure and function of the cholinergic system, and significant progress has also been made in elucidating the roles of neuronal and non-neuronal acetylcholine (ACh) in the pathogenesis and treatment of human disease [...].
Topics: Acetylcholine; Cholinergic Agents; Humans; Neurons; Signal Transduction
PubMed: 36144707
DOI: 10.3390/molecules27185971 -
Neuroscience Feb 2021In this review we will discuss the effect of two neuromodulatory transmitters, acetylcholine (ACh) and adenosine, on the synaptic release probability and short-term... (Review)
Review
In this review we will discuss the effect of two neuromodulatory transmitters, acetylcholine (ACh) and adenosine, on the synaptic release probability and short-term synaptic plasticity. ACh and adenosine differ fundamentally in the way they are released into the extracellular space. ACh is released mostly from synaptic terminals and axonal bouton of cholinergic neurons in the basal forebrain (BF). Its mode of action on synaptic release probability is complex because it activate both ligand-gated ion channels, so-called nicotinic ACh receptors and G-protein coupled muscarinic ACh receptors. In contrast, adenosine is released from both neurons and glia via nucleoside transporters or diffusion over the cell membrane in a non-vesicular, non-synaptic fashion; its receptors are exclusively G-protein coupled receptors. We show that ACh and adenosine effects are highly specific for an identified synaptic connection and depend mostly on the presynaptic but also on the postsynaptic receptor type and discuss the functional implications of these differences.
Topics: Acetylcholine; Cholinergic Agents; Presynaptic Terminals; Receptors, Muscarinic; Receptors, Nicotinic; Synaptic Transmission
PubMed: 32540364
DOI: 10.1016/j.neuroscience.2020.06.006 -
World Journal of Gastroenterology Jul 2022Cholinergic nerves are widely distributed throughout the human body and participate in various physiological activities, including sensory, motor, and visceral... (Review)
Review
Cholinergic nerves are widely distributed throughout the human body and participate in various physiological activities, including sensory, motor, and visceral activities, through cholinergic signaling. Cholinergic signaling plays an important role in pancreatic exocrine secretion. A large number of studies have found that cholinergic signaling overstimulates pancreatic acinar cells through muscarinic receptors, participates in the onset of pancreatic diseases such as acute pancreatitis and chronic pancreatitis, and can also inhibit the progression of pancreatic cancer. However, cholinergic signaling plays a role in reducing pain and inflammation through nicotinic receptors, but enhances the proliferation and invasion of pancreatic tumor cells. This review focuses on the progression of cholinergic signaling and pancreatic diseases in recent years and reveals the role of cholinergic signaling in pancreatic diseases.
Topics: Acute Disease; Cholinergic Agents; Humans; Pancreas; Pancreatitis; Receptors, Muscarinic
PubMed: 35978870
DOI: 10.3748/wjg.v28.i25.2910 -
Preface: Cholinergic mechanisms: This is the Preface for the special issue "Cholinergic Mechanisms".Journal of Neurochemistry Sep 2021This special issue of the Journal of Neurochemistry, entitled "Cholinergic Mechanisms," presents 15 reviews and two original papers, which have been selected to cover...
This special issue of the Journal of Neurochemistry, entitled "Cholinergic Mechanisms," presents 15 reviews and two original papers, which have been selected to cover the broad spectrum of topics and disciplines presented at the XVIth International Symposium on Cholinergic Mechanisms (ISCM-XVI), ranging from the molecular and the cellular to the clinical and the cognitive mechanisms of cholinergic transmission. The authors discuss recent developments in the field, for instance, the association of cholinergic transmission with a number of important neurological and neuromuscular diseases in the central and peripheral nervous systems.
Topics: Acetylcholine; Animals; Brain; Cholinergic Agents; Cholinergic Neurons; Humans; Peripheral Nervous System; Synaptic Transmission
PubMed: 34458988
DOI: 10.1111/jnc.15480 -
Respiratory Medicine 2019Tiotropium is a long-acting muscarinic antagonist approved for maintenance treatment of asthma in children, adolescents, and adults in the United States, and recommended... (Review)
Review
OBJECTIVE
Tiotropium is a long-acting muscarinic antagonist approved for maintenance treatment of asthma in children, adolescents, and adults in the United States, and recommended as add-on treatment for uncontrolled asthma despite treatment with inhaled corticosteroids and/or long-acting beta-2 agonists. This review traces the journey of tiotropium from its historical origins through early preclinical testing to human clinical trials and real-life studies.
DATA SOURCES
A search was performed in PubMed using search terms 'tiotropium' and 'asthma.' Relevant references cited in those articles were reviewed.
STUDY SELECTIONS
English language articles published from December 2008-December 2018 were screened. Articles evaluating the efficacy, cost-effectiveness, real-life evidence, and steroid-sparing effect of tiotropium with inadequately controlled asthma were included.
RESULTS
Anticholinergics have a long history of use in the treatment of obstructive airway diseases. Evidence indicates that tiotropium's mechanism of action consists of bronchodilation and diminished mucus secretion, with preclinical evidence suggesting an anti-inflammatory effect as well. Phase 2 and 3 clinical trials have demonstrated that tiotropium is efficacious and safe, resulting in significant improvements in lung function in adults, adolescents, and children across asthma severities. Emerging evidence suggests that add-on tiotropium might potentially enable reductions in inhaled corticosteroid dose in patients with uncontrolled asthma. Further, tiotropium is a cost-effective treatment option that is also effective in the clinical practice setting.
CONCLUSIONS
An increasing body of evidence indicates that tiotropium can play a significant role in the treatment of patients with uncontrolled asthma.
Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Child; Cholinergic Antagonists; Clinical Trials as Topic; Cost-Benefit Analysis; Expectorants; Humans; Muscarinic Antagonists; Prevalence; Tiotropium Bromide; Treatment Outcome; United States; Young Adult
PubMed: 31212121
DOI: 10.1016/j.rmed.2019.06.008