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Trends in Molecular Medicine Sep 2016Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of... (Review)
Review
Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of suppressing inflammation but can also induce metabolic syndrome-related processes. We summarize here evidence linking miRNA pathways which share regulatory networks in metabolic and anxiety-related conditions. In particular, miRNAs involved in these disorders include regulators of acetylcholine signaling in the nervous system and their accompanying molecular machinery. These have been associated with anxiety-prone states in individuals, while also acting as inflammatory suppressors. In peripheral tissues, altered miRNA pathways can lead to dysregulated metabolism. Common pathways in metabolic and anxiety-related phenomena might offer an opportunity to reclassify 'healthy' and 'unhealthy', as well as metabolic and anxiety-prone biological states, and inform putative strategies to treat these disorders.
Topics: Acetylcholine; Animals; Anxiety; Gene Expression Regulation; Humans; Inflammation; Metabolic Diseases; MicroRNAs; Signal Transduction
PubMed: 27496210
DOI: 10.1016/j.molmed.2016.07.001 -
The Journal of Investigative Dermatology Dec 2022The M3 muscarinic acetylcholine receptor is predominantly expressed in the basal epidermal layer where it mediates the effects of the autocrine/paracrine cytotransmitter...
The M3 muscarinic acetylcholine receptor is predominantly expressed in the basal epidermal layer where it mediates the effects of the autocrine/paracrine cytotransmitter acetylcholine. Patients with the autoimmune blistering disease pemphigus develop autoantibodies to M3 muscarinic acetylcholine receptor and show alterations in keratinocyte adhesion, proliferation, and differentiation, suggesting that M3 muscarinic acetylcholine receptor controls these cellular functions. Chmr3 mice display altered epidermal morphology resembling that seen in patients with pemphigus vulgaris. In this study, we characterized the cellular and molecular mechanisms through which M3 muscarinic acetylcholine receptor controls epidermal structure and function. We used single-cell RNA sequencing to evaluate keratinocyte heterogeneity and identify differentially expressed genes in specific subpopulations of epidermal cells in Chmr3 neonatal mice. We found that Chmr3 mice feature abnormal epidermal morphology characterized by accumulation of nucleated basal cells, shrinkage of basal keratinocytes, and enlargement of intercellular spaces. These morphologic changes were associated with upregulation of cell proliferation genes and downregulation of genes contributing to epidermal differentiation, extracellular matrix formation, intercellular adhesion, and cell arrangement. These findings provide, to our knowledge, previously unreported insights into how acetylcholine controls epidermal differentiation and lay a groundwork for future translational studies evaluating the therapeutic potential of cholinergic drugs in dermatology.
Topics: Animals; Mice; Acetylcholine; Epidermal Cells; Epidermis; Keratinocytes; Pemphigus; Receptor, Muscarinic M3
PubMed: 35870560
DOI: 10.1016/j.jid.2022.06.013 -
Neuropsychologia Feb 2020Why do we sometimes easily retrieve memories, but other times appear to forget them? We often look to our external environment for retrieval cues, but another way to... (Review)
Review
Why do we sometimes easily retrieve memories, but other times appear to forget them? We often look to our external environment for retrieval cues, but another way to optimize memory retrieval is to be in a mental state, or mode, that prioritizes access to our internal representation of the world. Such a 'retrieval mode' was proposed by Endel Tulving (1983), who considered it a neurocognitive state in which one keeps the goal of memory retrieval in mind. Building on Tulving's proposal, we review converging evidence from multiple lines of research that emphasize the importance of internal states in the instantiation of retrieval modes that optimize successful remembering. We identify three key factors that contribute to a retrieval mode by modulating either the likelihood or the content of retrieval: (1) an intention to remember or forget (either in the present or the future), (2) attentional selection of goal-relevant memories and suppression of distractors, and (3) fluctuating levels of acetylcholine in the hippocampus. We discuss empirical evidence that these internal states individually influence memory retrieval and propose how they may interact synergistically. Characterizing these dynamic internal factors is an important key for unlocking our understanding of the organization and accessibility of our memories.
Topics: Acetylcholine; Attention; Goals; Hippocampus; Humans; Intention; Mental Recall
PubMed: 31887313
DOI: 10.1016/j.neuropsychologia.2019.107328 -
Surgical Oncology Dec 2019Acetylcholine (ACh) was first identified as a classic neuromodulator and transmit signals through two subgroups of receptors, namely muscarinic receptors (mAChRs) and... (Review)
Review
Acetylcholine (ACh) was first identified as a classic neuromodulator and transmit signals through two subgroups of receptors, namely muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs). Apart from its well-established physiological role in central nervous system (CNS) and peripheral nervous system (PNS), autonomic nervous system and neuromuscular junction, the widely distributed expression of AChRs in different human organs suggests roles in other biological processes in addition to synaptic transmission. Accumulating evidence revealed that cancer cell processes such as proliferation, apoptosis, angiogenesis and even epithelial-mesenchymal transition (EMT) are mediated by overexpression of AChRs in different kinds of tumors. In breast cancer, α7-nAChR and α9-nAChR were reported to be oncogenic. On the other hand, research on the role of mAChRs in breast cancer tumorgenesis is limited and confined to M3 receptor only. Since AChRs distributed in both CNS and PNS even non-neuronal tissues, there is an urgent need for the development of subtype-specific AChR antagonist which inhibits cancer cell progression with minimal intervention on the normal acetylcholine-regulated system within human body.
Topics: Acetylcholine; Animals; Epithelial-Mesenchymal Transition; Humans; Neoplasms; Receptors, Cholinergic; Signal Transduction
PubMed: 31536927
DOI: 10.1016/j.suronc.2019.09.003 -
European Journal of Pharmacology Apr 2015Bipolar disorder is a unique illness characterized by fluctuations between mood states of depression and mania. Originally, an adrenergic-cholinergic balance hypothesis... (Review)
Review
Bipolar disorder is a unique illness characterized by fluctuations between mood states of depression and mania. Originally, an adrenergic-cholinergic balance hypothesis was postulated to underlie these different affective states. In this review, we update this hypothesis with recent findings from human and animal studies, suggesting that a catecholaminergic-cholinergic hypothesis may be more relevant. Evidence from neuroimaging studies, neuropharmacological interventions, and genetic associations support the notion that increased cholinergic functioning underlies depression, whereas increased activations of the catecholamines (dopamine and norepinephrine) underlie mania. Elevated functional acetylcholine during depression may affect both muscarinic and nicotinic acetylcholine receptors in a compensatory fashion. Increased functional dopamine and norepinephrine during mania on the other hand may affect receptor expression and functioning of dopamine reuptake transporters. Despite increasing evidence supporting this hypothesis, a relationship between these two neurotransmitter systems that could explain cycling between states of depression and mania is missing. Future studies should focus on the influence of environmental stimuli and genetic susceptibilities that may affect the catecholaminergic-cholinergic balance underlying cycling between the affective states. Overall, observations from recent studies add important data to this revised balance theory of bipolar disorder, renewing interest in this field of research.
Topics: Acetylcholine; Animals; Bipolar Disorder; Brain; Catecholamines; Humans
PubMed: 25107282
DOI: 10.1016/j.ejphar.2014.05.063 -
Archives of Biochemistry and Biophysics Nov 2023Membrane cholesterol oxidation is a hallmark of redox and metabolic imbalance, and it may accompany neurodegenerative disorders. Using microelectrode recordings of...
Membrane cholesterol oxidation is a hallmark of redox and metabolic imbalance, and it may accompany neurodegenerative disorders. Using microelectrode recordings of postsynaptic responses as well as fluorescent dyes for monitoring synaptic vesicle cycling and membrane properties, the action of enzymatic cholesterol oxidation on neuromuscular transmission was studied in the mice diaphragms. Cholesterol oxidase (ChO) at low concentration disturbed lipid-ordering specifically in the synaptic membranes, but it did not change markedly spontaneous exocytosis and evoked release in response to single stimuli. At low external Ca conditions, analysis of single exocytotic events revealed a decrease in minimal synaptic delay and the probability of exocytosis upon plasmalemmal cholesterol oxidation. At moderate- and high-frequency activity, ChO treatment enhanced both neurotransmitter and FM-dye release. Furthermore, it precluded a change in exocytotic mode from full-fusion to kiss-and-run during high-frequency stimulation. Accumulation of extracellular acetylcholine (without stimulation) dependent on vesamicol-sensitive transporters was suppressed by ChO. The effects of plasmalemmal cholesterol oxidation on both neurotransmitter/dye release at intense activity and external acetylcholine levels were reversed when synaptic vesicle membranes were also exposed to ChO (i.e., the enzyme treatment was combined with induction of exo-endocytotic cycling). Thus, we suggest that plasmalemmal cholesterol oxidation affects exocytotic machinery functioning, enhances synaptic vesicle recruitment to the exocytosis and decreases extracellular neurotransmitter levels at rest, whereas ChO acting on synaptic vesicle membranes suppresses the participation of the vesicles in the subsequent exocytosis and increases the neurotransmitter leakage. The mechanisms underlying ChO action can be related to the lipid raft disruption.
Topics: Mice; Animals; Cholesterol Oxidase; Acetylcholine; Synaptic Transmission; Neuromuscular Junction; Cholesterol; Neurotransmitter Agents
PubMed: 37955112
DOI: 10.1016/j.abb.2023.109803 -
Topics in Current Chemistry (Cham) May 2023Acetylcholine (ACh) is one of the most crucial neurotransmitters of the cholinergic system found in vertebrates and invertebrates and is responsible for many processes... (Review)
Review
Acetylcholine (ACh) is one of the most crucial neurotransmitters of the cholinergic system found in vertebrates and invertebrates and is responsible for many processes in living organisms. Disturbances in ACh transmission are closely related to dementia in Alzheimer's and Parkinson's disease. ACh in biological samples is most often determined using chromatographic techniques, radioenzymatic assays, enzyme-linked immunosorbent assay (ELISA), or potentiometric methods. An alternative way to detect and determine acetylcholine is applying spectroscopic techniques, due to low limits of detection and quantification, which is not possible with the methods mentioned above. In this review article, we described a detailed overview of different spectroscopic methods used to determine ACh with a collection of validation parameters as a perspective tool for routine analysis, especially in basic research on animal models on central nervous system. In addition, there is a discussion of examples of other biological materials from clinical and preclinical studies to give the whole spectrum of spectroscopic methods application. Descriptions of the developed chemical sensors, as well as the use of flow technology, were also presented. It is worth emphasizing the inclusion in the article of multi-component analysis referring to other neurotransmitters, as well as the description of the tested biological samples and extraction procedures. The motivation to use spectroscopic techniques to conduct this type of analysis and future perspectives in this field are briefly discussed.
Topics: Animals; Acetylcholine; Spectrum Analysis
PubMed: 37169979
DOI: 10.1007/s41061-023-00426-9 -
Journal of Cardiology Jul 2016Pharmacological spasm provocation tests are invasive methods and we always have the potential to encounter complications when performing these tests. In 1980, Buxton et... (Review)
Review
Pharmacological spasm provocation tests are invasive methods and we always have the potential to encounter complications when performing these tests. In 1980, Buxton et al. reported three deaths when they performed intravenous ergonovine testing. However, we now employ the intracoronary ergonovine test instead of the intravenous injection of ergonovine from a safety procedure point of view. Past serious major complications of intravenous ergonovine tests, intracoronary ergonovine tests, and intracoronary acetylcholine tests were 0.31% (26/8419), 0.51% (11/2173), and 0.95% (148/15,527), respectively. Selective intracoronary testing had the serious major complications in 0.89% of patients including just one death (0.006%) and two acute myocardial infarctions (0.01%). Selective spasm provocation tests had no additional risks compared with performing diagnostic coronary angiography alone. In the Western countries, the pharmacological spasm provocation tests are not familiar in the clinic except for some specialized institutions. We need international clinical studies using the same protocol of spasm provocation tests to compare the frequency, clinical features, and prognosis of acetylcholine- or ergonovine-provoked coronary spasm between Western and Asian countries. And we hope that Western guidelines give spasm provocation testing a class I indication similar to Japanese Circulation Society guidelines because coronary artery spasm may have fewer racial differences and borders.
Topics: Acetylcholine; Coronary Angiography; Coronary Vasospasm; Ergonovine; Female; Heart Function Tests; Humans; Injections, Intra-Arterial; Male; Middle Aged; Practice Guidelines as Topic; Vasodilator Agents
PubMed: 27234219
DOI: 10.1016/j.jjcc.2016.03.005 -
Journal of Neurochemistry Aug 2017Bacteria and archaea synthesize acetylcholine (ACh). Thus, it can be postulated that ACh was created by nature roughly three billion years ago. Therefore, the wide... (Review)
Review
Bacteria and archaea synthesize acetylcholine (ACh). Thus, it can be postulated that ACh was created by nature roughly three billion years ago. Therefore, the wide expression of ACh in nature (i.e., in bacteria, archaea, unicellular organisms, plants, fungi, non-vertebrates and vertebrates and in the abundance of non-neuronal cells of mammals) is not surprising. The term non-neuronal ACh and non-neuronal cholinergic system have been introduced to describe the auto- and paracrine, that is, local regulatory actions of ACh in cells not innervated by neuronal cholinergic fibers and to communicate among themselves. In this way non-neuronal ACh binds to the nicotinic or muscarinic receptors expressed on these local and migrating cells and modulates basic cells functions such as proliferation, differentiation, migration and the transport of ions and water. The present article is focused to the effects of non-neuronal ACh linked to reproduction; data on the expression and function of the non-neuronal cholinergic system in the following topics are summarized: (i) Sperm, granulosa cells, oocytes; (ii) Auxiliary systems (ovary, oviduct, placenta); (iii) Embryonic stem cells as first step for reproduction of a new individual after fertilization; (iv) Larval food as an example of reproduction in insects (honeybees) and adverse effects of the neonicotinoids, a class of world-wide applied insecticides. The review article will show that non-neuronal ACh is substantially involved in the regulation of reproduction in mammals and also non-mammals like insects (honeybees). There is a need to learn more about this biological role of ACh. In particular, we have to consider that insecticides like the neonicotinoids, but also carbamates and organophosphorus pesticides, interfere with the non-neuronal cholinergic system thus compromising for example the breeding of honeybees. But it is possible that other species may also be adversely affected as well, a mechanism which may contribute to the observed decline in biodiversity. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
Topics: Acetylcholine; Animals; Cell Movement; Humans; Insecticides; Mammals; Nicotine; Receptors, Muscarinic
PubMed: 28072454
DOI: 10.1111/jnc.13953 -
The Journal of Physiology Jun 2024Play is a suite of apparently non-functional, pleasurable behaviours observed in human and non-human animals. Although the phenomenon has been studied extensively, no... (Review)
Review
Play is a suite of apparently non-functional, pleasurable behaviours observed in human and non-human animals. Although the phenomenon has been studied extensively, no adaptationist behavioural theory of how play evolved can be supported by the available evidence. However, the advancement of the extended evolutionary synthesis and developments in systems biology offer alternative avenues for non-adaptationist physiological hypotheses. I therefore propose a hypothesis of play, based upon a complex ACh activity that is under agential control of the organism, whereby play initiates ACh-mediated feedforward and feedback processes which act to: (i) regulate metabolic processes; (ii) form new ACh receptors via ACh mRNA activity; (iii) mediate attention, memory consolidation and learning; and (iv) mediate social behaviours, reproduction and embryonic development. However, play occurs across taxa, but does not occur across all taxonomic groups or within all species of a taxonomic group. Thus, to support the validity of the proposed hypothesis, I further propose potential explanations for this anomaly, which include sampling and observer biases, altricial versus precocial juvenile development, and the influence of habitat niche and environmental conditions on behaviour. The proposed hypothesis thus offers new avenues for study in both the biological and social sciences, in addition to having potential applications in applied sciences, such as animal welfare and biomedical research. Crucially, it is hoped that this hypothesis will promote further study of a valid and behaviourally significant, yet currently enigmatic, biological phenomenon.
Topics: Animals; Humans; Play and Playthings; Behavior, Animal; Biological Evolution; Acetylcholine; Social Behavior; Adaptation, Physiological
PubMed: 37656171
DOI: 10.1113/JP284413