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Neurochemical Research Oct 2023Astrocytes release numerous factors known to contribute to the process of synaptogenesis, yet knowledge about the signals that control their release is limited. We...
Astrocytes release numerous factors known to contribute to the process of synaptogenesis, yet knowledge about the signals that control their release is limited. We hypothesized that neuron-derived signals stimulate astrocytes, which respond to neurons through the modulation of astrocyte-released synaptogenic factors. Here we investigate the effect of cholinergic stimulation of astrocytes on synaptogenesis in co-cultured neurons. Using a culture system where primary rat astrocytes and primary rat neurons are first grown separately allowed us to independently manipulate astrocyte cholinergic signaling. Subsequent co-culture of pre-stimulated astrocytes with naïve neurons enabled us to assess how prior stimulation of astrocyte acetylcholine receptors uniquely modulates neuronal synapse formation. Pre-treatment of astrocytes with the acetylcholine receptor agonist carbachol increased the expression of synaptic proteins, the number of pre- and postsynaptic puncta, and the number of functional synapses in hippocampal neurons after 24 h in co-culture. Astrocyte secretion of the synaptogenic protein thrombospondin-1 increased after cholinergic stimulation and inhibition of the receptor for thrombospondins prevented the increase in neuronal synaptic structures. Thus, we identified a novel mechanism of neuron-astrocyte-neuron communication, where neuronal release of acetylcholine stimulates astrocytes to release synaptogenic proteins leading to increased synaptogenesis in neurons. This study provides new insights into the role of neurotransmitter receptors in developing astrocytes and into our understanding of the modulation of astrocyte-induced synaptogenesis.
Topics: Rats; Animals; Astrocytes; Synapses; Neurons; Coculture Techniques; Cholinergic Agents
PubMed: 37402036
DOI: 10.1007/s11064-023-03979-9 -
Neuroscience and Biobehavioral Reviews Sep 2023Sensory systems are highly plastic, but the mechanisms of sensory plasticity remain unclear. People with vision or hearing loss demonstrate significant neural network... (Review)
Review
Sensory systems are highly plastic, but the mechanisms of sensory plasticity remain unclear. People with vision or hearing loss demonstrate significant neural network reorganization that promotes adaptive changes in other sensory modalities as well as in their ability to combine information across the different senses (i.e., multisensory integration. Furthermore, sensory network remodeling is necessary for sensory restoration after a period of sensory deprivation. Acetylcholine is a powerful regulator of sensory plasticity, and studies suggest that cholinergic medications may improve visual and auditory abilities by facilitating sensory network plasticity. There are currently no approved therapeutics for sensory loss that target neuroplasticity. This review explores the systems-level effects of cholinergic signaling on human visual and auditory perception, with a focus on functional performance, sensory disorders, and neural activity. Understanding the role of acetylcholine in sensory plasticity will be essential for developing targeted treatments for sensory restoration.
Topics: Humans; Acetylcholine; Deafness; Auditory Perception; Cholinergic Agents; Hearing Loss; Neuronal Plasticity; Visual Perception; Sensory Deprivation
PubMed: 37467908
DOI: 10.1016/j.neubiorev.2023.105323 -
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 -
International Journal of Molecular... Feb 2021Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It... (Review)
Review
Mushroom poisoning has always been a threat to human health. There are a large number of reports about ingestion of poisonous mushrooms every year around the world. It attracts the attention of researchers, especially in the aspects of toxin composition, toxic mechanism and toxin application in poisonous mushroom. is a large genus of mushrooms and contains toxic substances including muscarine, psilocybin, psilocin, aeruginascin, lectins and baeocystin. In order to prevent and remedy mushroom poisoning, it is significant to clarify the toxic effects and mechanisms of these bioactive substances. In this review article, we summarize the chemistry, most known toxic effects and mechanisms of major toxic substances in mushrooms, especially muscarine, psilocybin and psilocin. Their available toxicity data (different species, different administration routes) published formerly are also summarized. In addition, the treatment and medical application of these toxic substances in mushrooms are also discussed. We hope that this review will help understanding of the chemistry and toxicology of mushrooms as well as the potential clinical application of its bioactive substances to benefit human beings.
Topics: Agaricales; Animals; Humans; Lectins; Muscarine; Mushroom Poisoning; Organophosphorus Compounds; Psilocybin; Tryptamines
PubMed: 33672330
DOI: 10.3390/ijms22042218 -
Physiological Research Sep 2017Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune... (Review)
Review
Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.
Topics: Animals; Anti-Inflammatory Agents; Cholinergic Agents; Cholinergic Neurons; Humans; Inflammation; Neuroimmunomodulation; Signal Transduction; Vagus Nerve
PubMed: 28937230
DOI: 10.33549/physiolres.933671 -
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 -
Acta Physiologica (Oxford, England) Nov 2022Cardiac autonomic nervous system (ANS) dysregulation is a hallmark of several cardiovascular diseases. Adrenergic signaling enhanced cardiomyocyte cohesion via...
AIM
Cardiac autonomic nervous system (ANS) dysregulation is a hallmark of several cardiovascular diseases. Adrenergic signaling enhanced cardiomyocyte cohesion via PKA-mediated plakoglobin phosphorylation at serine 665, referred to as positive adhesiotropy. This study investigated cholinergic regulation of cardiomyocyte cohesion using muscarinic receptor agonist carbachol (CCH).
METHODS
Dissociation assays, Western blot analysis, immunostaining, atomic force microscopy (AFM), immunoprecipitation, transmission electron microscopy (TEM), triton assays, and siRNA knockdown of genes were performed in either HL-1 cells or plakoglobin (PG) wild type (Jup ) and knockout (Jup ) mice, which served as a model for arrhythmogenic cardiomyopathy.
RESULTS
In HL-1 cells grown in norepinephrine (NE)-containing medium for baseline adrenergic stimulation, and murine cardiac slice cultures from Jup and Jup mice CCH treatment impaired cardiomyocyte cohesion. Immunostainings and AFM experiments revealed that CCH reduced desmoglein 2 (DSG2) localization and binding at cell borders. Furthermore, CCH reduced intercalated disc plaque thickness in both Jup and Jup mice, evidenced by TEM analysis. Immunoprecipitation experiments in HL-1 cells revealed no changes in DSG2 interaction with desmoplakin (DP), plakophilin 2 (PKP2), PG, and desmin (DES) after CCH treatment. However, knockdown of any of the above proteins abolished CCH-mediated loss of cardiomyocyte cohesion. Furthermore, in HL-1 cells, CCH inhibited adrenergic-stimulated ERK phosphorylation but not PG phosphorylation at serine 665. In addition, CCH activated the AKT/GSK-3β axis in the presence of NE.
CONCLUSION
Our results demonstrate that cholinergic signaling antagonizes the positive effect of adrenergic signaling on cardiomyocyte cohesion and thus causes negative adhesiotropy independent of PG phosphorylation.
Topics: Mice; Animals; Myocytes, Cardiac; Desmoglein 2; gamma Catenin; Glycogen Synthase Kinase 3 beta; Desmoplakins; Carbachol; Proto-Oncogene Proteins c-akt; Plakophilins; RNA, Small Interfering; Desmin; Cholinergic Agents; Receptors, Muscarinic; Adrenergic Agents; Norepinephrine; Serine
PubMed: 36039679
DOI: 10.1111/apha.13881 -
Journal of Physiology and Pharmacology... Dec 2018Acrylamide (ACR) is a chemical compound, that forms in starchy food products during cooking at high-temperatures, including frying, baking, and roasting. ACR is a known... (Review)
Review
Acrylamide (ACR) is a chemical compound, that forms in starchy food products during cooking at high-temperatures, including frying, baking, and roasting. ACR is a known lethal neurotoxin. The presented review suggests that the mechanism of ACR's neurotoxicity may be related to an impaired cholinergic transmission in the central and peripheral nervous system and redox imbalance. These may not only affect ongoing brain functions but also participate in etiology of neurodegeneration.
Topics: Acrylamide; Animals; Cholinergic Agents; Humans; Nervous System; Neurotoxins
PubMed: 30898983
DOI: 10.26402/jpp.2018.6.03 -
Neuroscience and Biobehavioral Reviews Aug 2015An increasing body of evidence has implicated the central muscarinic system as contributing to a number of symptoms of schizophrenia and serving as a potential target... (Review)
Review
An increasing body of evidence has implicated the central muscarinic system as contributing to a number of symptoms of schizophrenia and serving as a potential target for pharmaceutical interventions. A theoretical review is presented that focuses on the central muscarinic system's contribution to the cognitive symptoms of schizophrenia. The aim is to bridge the void between pertinent neuropsychological and neurobiological research to provide an explanatory account of the role that the central muscarinic system plays in the symptoms of schizophrenia. First, there will be a brief overview of the relevant neuropsychological schizophrenia literature, followed by a concise introduction to the central muscarinic system. Subsequently, we will draw from animal, neuropsychological and pharmacological literature, and discuss the findings in relation to cognition, schizophrenia and the muscarinic system. Whilst unifying the multiple domains of research into a concise review will act as a useful line of enquiry into the central muscarinic systems contribution to the symptoms of schizophrenia, it will be made apparent that more research is needed in this field.
Topics: Acetylcholine; Animals; Brain; Cholinergic Agents; Cognition; Humans; Receptors, Muscarinic; Schizophrenia; Schizophrenic Psychology
PubMed: 26003527
DOI: 10.1016/j.neubiorev.2015.05.011 -
The Cochrane Database of Systematic... Mar 2018Tardive dyskinesia (TD) remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that TD could have a component... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tardive dyskinesia (TD) remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that TD could have a component of central cholinergic deficiency. Cholinergic drugs have been used to treat TD.
OBJECTIVES
To determine the effects of cholinergic drugs (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86, tacrine, metoxytacrine, galantamine, ipidacrine, donepezil, rivastigmine, eptastigmine, metrifonate, xanomeline, cevimeline) for treating antipsychotic-induced TD in people with schizophrenia or other chronic mental illness.
SEARCH METHODS
An electronic search of the Cochrane Schizophrenia Group's Study-Based Register of Trials (16 July 2015 and April 2017) was undertaken. This register is assembled by extensive searches for randomised controlled trials in many electronic databases, registers of trials, conference proceedings and dissertations. References of all identified studies were searched for further trial citations.
SELECTION CRITERIA
We included reports identified by the search if they were of controlled trials involving people with antipsychotic-induced TD and chronic mental illness, who had been randomly allocated to either a cholinergic agent or to a placebo or no intervention. Two review authors independently assessed the methodological quality of the trials.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and, where possible, estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We analysed data on an intention-to-treat basis, with the assumption that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
We included 14 studies investigating the use of cholinergic drugs compared with placebo published between 1976 and 2014. All studies involved small numbers of participants (five to 60 people). Three studies that investigated the new cholinergic Alzheimer drugs for the treatment of TD are new to this update. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, we are unsure if data are incomplete, and data were often poorly or selectively reported.We are uncertain about the effect of new or old cholinergic drugs on no clinically important improvement in TD symptoms when compared with placebo; the quality of evidence was very low (RR 0.89, 95% CI 0.65 to 1.23; 27 people, 4 RCTs). Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (low-quality evidence, RR 1.11, 95% CI 0.55 to 2.24; 147 people). Again, due to very low-quality evidence, we are uncertain about the effects on mental state (RR 0.50, 95% CI 0.10 to 2.61; 77 people, 5 RCTs), adverse events (RR 0.56, 95% CI 0.15 to 2.14; 106 people, 4 RCTs), and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 288 people 12 RCTs). No study reported on social confidence, social inclusion, social networks, or personalised quality of life.
AUTHORS' CONCLUSIONS
TD remains a major public health problem. The clinical effects of both older cholinergic drugs and new cholinergic agents, now used for treating Alzheimer's disease, are unclear, as too few, too small studies leave many questions unanswered. Cholinergic drugs should remain of interest to researchers and currently have little place in routine clinical work. However, with the advent of new cholinergic agents now used for treating Alzheimer's disease, scope exists for more informative trials. If these new cholinergic agents are to be investigated for treating people with TD, their effects should be demonstrated in large well-designed, conducted and reported randomised trials.
Topics: Antipsychotic Agents; Cholinergic Agents; Dyskinesia, Drug-Induced; Humans; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 29553158
DOI: 10.1002/14651858.CD000207.pub2