Acetylcholine Synthesis Research Articles

Implications of the non-neuronal cholinergic system for therapeutic interventions of inflammatory skin diseases.

The pivotal roles of acetylcholine (ACh) in physiological processes encompass both the nervous and non-neuronal cholinergic systems (NNCS). This review delineates the synthesis, release, receptor interactions, and degradation of ACh within the nervous system, and explores the NNCS in depth within skin cells including keratinocytes, endothelial cells, fibroblasts, macrophages, and other immune cells. We highlight the NNCS's essential functions in maintaining epidermal barrier integrity, promoting wound healing, regulating microcirculation, and modulating inflammatory responses. The potential of the NNCS as a therapeutic target for localized ACh regulation in the skin is discussed, though the translation of these findings into clinical practice remains uncertain due to the complexity of cholinergic signalling and the lack of comprehensive human studies. The review progresses to therapeutic modulation strategies of the NNCS, including AChE inhibitors, nicotinic and muscarinic receptor agonists and antagonists, choline uptake enhancers, and botulinum toxin, highlighting their relevance in dermatology. We highlight the impact of the NNCS on prevalent skin diseases such as psoriasis, atopic dermatitis, rosacea, acne, bullous diseases, hyperhidrosis and hypohidrosis, illustrating its significance in disease pathogenesis and therapy. This comprehensive overview aims to enhance understanding of the NNCS's role in skin health and disease, offering a foundation for future research and therapeutic innovation.

Comprehending the Rationale for Repurposing Type 2 Diabetes Mellitus Medicines for Alzheimer's Disease Patients Via Gene Networks Studies and its Associated Molecular Pathways

Type 2 Diabetes Mellitus (T2DM) is a known risk factor for Alzheimer’s disease (AD). Several epidemiological studies have reported a pathological association between AD and T2DM and have declared AD as a comorbidity of T2DM making T2DM a major risk factor for AD. Impaired insulin signaling elevates the risk for AD development and this can result in neurodegeneration via Aβ formation or increased inflammation in response to intraneural β amyloid. Insulin resistance, impaired glucose, carbohydrate and protein metabolism, and mitochondrial dysfunction are some characteristics common to both AD and T2DM. These features appear much before the clinical examination of both neurodegenerative diseases. It has now become extremely crucial to know the events that appear in the prodromal phases of these neurodegenerative disorders that elevate neurodegeneration risk. This has given rise to the idea that medications designed to treat T2DM may also help to alter the pathophysiology of AD and maintain cognitive function. This review highlights the recent and past evidence that correlates AD and T2DM, focusing on the shared pathogenic processes, and then evaluates the numerous medications given at clinical stages for assessing their potential activity in AD. Few molecular processes and their associated genes, altered protein metabolism (IAPP, Fyn/ERK/S6), altered carbohydrate metabolism (GLUT1, GLUT3, GLUT4), Impaired Acetylcholine (Ach) Synthesis (ACHE, ChAT), altered cholesterol metabolism (APOE4) were some of the biological reasons which made T2DM drugs useful for AD at the molecular level. Additionally, an in-silico strategy explores and evaluates the efficiency of T2DM medications like metformin, insulin, thiazolidinediones, etc. for AD treatment. The gene receptors for these drugs in the human system were predicted to understand the molecular pathways followed by these receptors which are common in AD pathology.

Production of Acetylcholine by Podocytes and its Protection from Kidney Injury in Glomerulonephritis.

One of the most important factors modulating endothelial health is acetylcholine, and while it is associated as a cholinergic neurotransmitter; it is also expressed by non-neuronal cells. However, its role in the kidney, which does not receive cholinergic innervation, remains unknown. To determine if acetylcholine is produced in the kidney, we used ChAT(BAC)-eGFP (ChAT mice) transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed under the control of the endogenous choline acetyltransferase (ChAT) transcriptional regulatory elements. We then investigated the role of acetylcholine in kidney disease by inducing anti- glomerular basement membrane glomerulonephritis (anti-GBM GN) in ChAT transgenic mice. We demonstrate ChAT, the sole enzyme responsible for acetylcholine production, was expressed in glomerular podocytes and produced acetylcholine. We also show during anti-GBM GN in ChAT transgenic mice, ChAT expression was induced in the glomeruli, mainly in podocytes and protects mice from kidney injury with marked reduction of glomerular proliferation/fibrinoid necrosis (by 71%) crescent formation (by 98%), and tubular injury (by 78%). In contrast, specific knockout of podocyte ChAT worsened the severity of the disease. The mechanism of protection included reduction of inflammation, attenuation of angiogenic factors reduction, and increase of eNOS expression. In vitro and in vivo studies demonstrated available drugs like cholinesterase inhibitors and ChAT inducers increased the expression of podocyte-ChAT and acetylcholine production. These findings suggest de novo synthesis of acetylcholine by podocytes protected against inflammation and glomerular endothelium damage in anti-GBM glomerulonephritis.

Post-traumatic cognitive disorders: the cholinergic therapy options

Traumatic brain injury (TBI) is one of the most common causes of neurological disability in young and middle-aged people. Cognitive impairment is the most persistent and universal brain injury syndrome in cases of TBI and, moreover, the best indicator of TBI severity to predict its outcome. Cognitive impairment can persist persistently even after mild TBI, which accounts for 70–90 % of the total number of trauma patients. This may be due to the fact that in cases of mild TBI, the most fragile functions of integrative structures of the frontal and temporal lobes are slowly and not always completely recovered and the dominant clinical manifestation become complex neuropsychological disorders. Individuals with repeated mild TBI are characterized by development of chronic post-traumatic encephalopathy, that is a kind of neurodegenerative disease manifested by slowly increasing cognitive impairment, parkinsonism and a number of other neurological syndromes. Early detection and adequate correction of the cognitive impairments may improve the outcome of injury of diverging severity. Due to the fact that the pathogenesis of TBI is based on disorder of cholinergic system, the patients have predominance of regulatory disorders in the neuropsychological profile, as well as a combination of cognitive and affective disorders. Administration of acetylcholine precursors leads to rapid increase of free choline levels in plasma that penetrates the blood-brain barrier well and enhances cholinergic activity by increasing acetylcholine synthesis and release. The article considers the possibilities of using acetylcholine precursors in connection with their potential to block the progressive impairment of cognitive functions induced by trauma as well as to reduce severity of behavioral and affective disorders.

Congenital myasthenic syndrome secondary to pathogenic variants in the SLC5A7 gene: report of two cases

BackgroundCongenital Myasthenic Syndromes (CMS) are rare genetic diseases, which share as a common denominator muscle fatigability due to failure of neuromuscular transmission. A distinctive clinical feature of presynaptic CMS variants caused by defects of the synthesis of acetylcholine is the association with life-threatening episodes of apnea. One of these variants is caused by mutations in the SLC5A7 gene, which encodes the sodium-dependent HC-3 high-affinity choline transporter 1 (CHT1). To our knowledge there are no published cases of this CMS type in Latin America.Case presentationWe present two cases of CHT1-CMS. Both patients were males presenting with repeated episodes of apnea, hypotonia, weakness, ptosis, mild ophthalmoparesis, and bulbar deficit. The first case also presented one isolated seizure, while the second case showed global developmental delay. Both cases, exhibited incomplete improvement with treatment with pyridostigmine.ConclusionsThis report emphasizes the broad incidence of CMS with episodic apnea caused by mutations in the SLC5A7 gene and the frequent association of this condition with serious manifestations of central nervous system involvement.

Effects of Chronic Exposure to Low Doses of Rotenone on Dopaminergic and Cholinergic Neurons in the CNS of Hemigrapsus sanguineus.

Rotenone, as a common pesticide and insecticide frequently found in environmental samples, may be present in aquatic habitats worldwide. Exposure to low concentrations of this compound may cause alterations in the nervous system, thus contributing to Parkinsonian motor symptoms in both vertebrates and invertebrates. However, the effects of chronic exposure to low doses of rotenone on the activity of neurotransmitters that govern motor functions and on the specific molecular mechanisms leading to movement morbidity remain largely unknown for many aquatic invertebrates. In this study, we analyzed the effects that rotenone poisoning exerts on the activity of dopamine (DA) and acetylcholine (ACh) synthesis enzymes in the central nervous system (CNS) of Asian shore crab, Hemigrapsus sanguineus (de Haan, 1835), and elucidated the association of its locomotor behavior with Parkinson's-like symptoms. An immunocytochemistry analysis showed a reduction in tyrosine hydroxylase (TH) in the median brain and the ventral nerve cord (VNC), which correlated with the subsequent decrease in the locomotor activity of shore crabs. We also observed a variation in cholinergic neurons' activity, mostly in the ventral regions of the VNC. Moreover, the rotenone-treated crabs showed signs of damage to ChAT-lir neurons in the VNC. These data suggest that chronic treatment with low doses of rotenone decreases the DA level in the VNC and the ACh level in the brain and leads to progressive and irreversible reductions in the crab's locomotor activity, life span, and changes in behavior.

Thiazolium salt mimics the non-coenzyme effects of vitamin B1 in rat synaptosomes

Long-term studies have confirmed a causal relationship between the development of neurodegenerative processes and vitamin B1 (thiamine) deficiency. However, the biochemical mechanisms underlying the high neurotropic activity of thiamine are not fully understood. At the same time, there is increasing evidence that vitamin B1, in addition to its coenzyme functions, may have non-coenzyme activities that are particularly important for neurons. To elucidate which effects of vitamin B1 in neurons are due to its coenzyme function and which are due to its non-coenzyme activity, we conducted a comparative study of the effects of thiamine and its derivative, 3-decyloxycarbonylmethyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride (DMHT), on selected processes in synaptosomes. The ability of DMHT to effectively compete with thiamine for binding to thiamine-binding sites on the plasma membrane of synaptosomes and to participate as a substrate in the thiamine pyrophosphokinase reaction was demonstrated. In experiments with rat brain synaptosomes, unidirectional effects of DMHT and thiamine on the activity of the pyruvate dehydrogenase complex (PDC) and on the incorporation of radiolabeled [2–14C]pyruvate into acetylcholine were demonstrated. The observed effects of thiamine and DMHT on the modulation of acetylcholine synthesis can be explained by suggesting that both compounds, which interact in cells with enzymes of thiamine metabolism, are phosphorylated and exert an inhibitory/activating effect (concentration-dependent) on PDC activity by affecting the regulatory enzymes of the complex. Such effects were not observed in the presence of structural analogues of thiamine and DMHT without a 2-hydroxyethyl substituent at position 5 of the thiazolium cycle. The effect of DMHT on the plasma membrane Ca-ATPase was similar to that of thiamine. At the same time, DMHT showed high cytostatic activity against neuroblastoma cells.

Influence of supplemental choline on milk yield, fatty acid profile, and weight changes in postpartum ewes and their offspring.

The most intensive nutritional requirements occur during milk production's peak. Ewe milk contains more protein and fat than cow milk. The nutritional factors significantly determine the composition. The liver undergoes high stress during lactation but is relieved by essential nutrients. Choline acts metabolically as a lipotrope. This compound functions in cell structure construction, maintenance, and acetylcholine synthesis. The animal nutrition industry provides choline from various sources, such as synthetic and natural kinds. This study evaluated the influence of two distinct choline sources on dairy ewes' peripartum and postpartum milk production, composition, and offspring growth. Twenty-four Rambouillet ewes, each weighing around 63.7 ± 1.7 kg, aged three with two previous births, spent 30-day pre-partum and post-partum in individual pens (2 × 2 m). They were given different experimental treatments 30 days before and after birth according to a randomized design; no choline (a), 4 g/day rumen-protected choline (RPC) (b), or 4 g/day thiocholine (c). Milk samples for milk composition and long-chain fatty acid (FA) analysis were taken every 30 days during milk collection. Significant differences (p < 0.05) in ewe body weight, lamb birth weight, and 30-day-old lamb body weight were observed at lambing and on day 30 of lactation due to choline treatment. Milk yield was significantly higher (1.57 kg/day) compared to the control (1.02 kg/day) and RPC (1.39 kg/day), due to the herbal choline source. There was no significant difference in the milk's protein, lactose, fat, non-fat solids, and total milk solids content between the treatments. Herbal choline lowers (p < 0.05) the concentrations of caproic, caprylic, capric, lauric, and myristic acids while boosting (p < 0.05) those of oleic and cis-11-eicosenoic acid, the changes influencing long-chain FA levels (p < 0.05). Providing choline from both sources to ewes enhanced milk production and body weight at lambing and on 30-day post-lambing. The herbal choline supplement altered short-chain milk FAs, while representative concentration pathways affected medium-chain ones.

Dysregulated Cholinergic Signaling Inhibits Oligodendrocyte Maturation Following Demyelination.

Dysregulation of oligodendrocyte progenitor cell (OPC) recruitment and oligodendrocyte differentiation contribute to failure of remyelination in human demyelinating diseases such as multiple sclerosis (MS). Deletion of muscarinic receptor enhances OPC differentiation and remyelination. However, the role of ligand-dependent signaling versus constitutive receptor activation is unknown. We hypothesized that dysregulated acetylcholine (ACh) release upon demyelination contributes to ligand-mediated activation hindering myelin repair. Following chronic cuprizone (CPZ)-induced demyelination (male and female mice), we observed a 2.5-fold increase in ACh concentration. This increase in ACh concentration could be attributed to increased ACh synthesis or decreased acetylcholinesterase-/butyrylcholinesterase (BChE)-mediated degradation. Using choline acetyltransferase (ChAT) reporter mice, we identified increased ChAT-GFP expression following both lysolecithin and CPZ demyelination. ChAT-GFP expression was upregulated in a subset of injured and uninjured axons following intraspinal lysolecithin-induced demyelination. In CPZ-demyelinated corpus callosum, ChAT-GFP was observed in Gfap+ astrocytes and axons indicating the potential for neuronal and astrocytic ACh release. BChE expression was significantly decreased in the corpus callosum following CPZ demyelination. This decrease was due to the loss of myelinating oligodendrocytes which were the primary source of BChE. To determine the role of ligand-mediated muscarinic signaling following lysolecithin injection, we administered neostigmine, a cholinesterase inhibitor, to artificially raise ACh. We identified a dose-dependent decrease in mature oligodendrocyte density with no effect on OPC recruitment. Together, these results support a functional role of ligand-mediated activation of muscarinic receptors following demyelination and suggest that dysregulation of ACh homeostasis directly contributes to failure of remyelination in MS.

Cholinergic Mechanisms in Gastrointestinal Neoplasia.

Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia. Herein, after briefly reviewing the classification of acetylcholine-activated receptors and the role that nicotinic and muscarinic cholinergic signaling plays in normal digestive function, we consider the mechanics of acetylcholine synthesis and release by neuronal and non-neuronal cells in the gastrointestinal microenvironment, and current methodology and challenges in measuring serum and tissue acetylcholine levels accurately. Then, we critically evaluate the evidence that constitutive and ligand-induced activation of acetylcholine-activated receptors plays a role in promoting gastrointestinal neoplasia. We focus primarily on adenocarcinomas of the stomach, pancreas, and colon, because these cancers are particularly common worldwide and, when diagnosed at an advanced stage, are associated with very high rates of morbidity and mortality. Throughout this comprehensive review, we concentrate on identifying novel ways to leverage these observations for prognostic and therapeutic purposes.

Nasal solitary chemosensory cells govern daily rhythm in mouse model of allergic rhinitis

BackgroundWhile the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic. ObjectiveWe aim to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated. MethodsAR was induced in mice using the ovalbumin method. Toluidine blue staining, LC-MS/MS analysis, qPCR, and immunoblotting were performed with AR and control mice. ResultsOvalbumin-induced AR is diurnally rhythmic and associated with clock gene disruption in nasal mucosa. In particular, Rev-erbα is generally down-regulated, and its rhythm retained but with a near 12-h phase shift. Furthermore, global knockout of the core clock gene Bmal1 or Rev-erbα increases the susceptibility of mice to AR and blunts AR rhythmicity. Importantly, nasal SCCs (solitary chemosensory cells) are rhythmically activated, and inhibition of the SCC pathway leads to attenuated AR and a loss of its rhythm. Moreover, rhythmic activation of SCCs is accounted for by diurnal expression of ChAT (an enzyme responsible for the synthesis of acetylcholine) and temporal generation of the neurotransmitter acetylcholine. Mechanistically, REV-ERBα trans-represses Chat through direct binding to a specific response element, generating a diurnal oscillation in this target gene. ConclusionThese findings identify SCCs, under the control of REV-ERBα, as a driver of AR rhythmicity, and suggest targeting SCCs as a new avenue for AR management.

De novo transcriptome analysis of Protohermes xanthodes Navás (Megaloptera: Corydalidae) reveling the effects of sublethal chlorpyrifos on the expression of cholinergic neuronal genes

The insect cholinergic neuron system is the target for various pesticides, including organophosphate, carbamate and neonicotinoid pesticides. In this study, we conducted a de novo transcriptome analysis on the aquatic insect Protohermes xanthodes and identified for the first time presenting sixteen genes encoding cholinergic neuronal proteins (PxanChaT, PxanVAChT, PxanmAChR, PxannAChRs, and PxanAChEs), which are candidates for acetylcholine synthesis, transport, reception and degradation in cholinergic synapse. FPKM analysis revealed that these genes are primarily expressed in head and nerve cord of P. xanthodes larvae, and some of them are also abundant in hindgut, malpighian tubules and tracheae. After exposed to different concentrations of sublethal chlorpyrifos (CPF), expression of these cholinergic neuronal genes are generally increased and then decreased with the increase of CPF concentration, except PxannAChRα9 which is increased in both 4.2 and 8.4 μg/L CPF groups. Short-term (96 h) CPF exposure resulted in significant up-regulation of PxanAChE1 expression in P. xanthodes larvae exposed to 0.42 and 4.2 μg/L CPF concentrations, while PxanAChE2 was up-regulated only in 0.42 μg/L CPF group. After long-term (14 d) CPF exposure, PxanAChE1 expression was down-regulated in 0.168 and 0.42 μg/L CPF groups. PxanAChE2 expression was dramatically decreased in all CPF groups. Moreover, acetylcholinesterase (AChE) activity was significantly decreased across all long-term CPF exposure groups. These results suggested that sublethal exposure to CPF can disrupt the expression of cholinergic neuronal genes in P. xanthodes larvae, and implied that long-term sublethal CPF exposure may cause toxic effects on P. xanthodes larvae by inhibiting AChE activity. Furthermore, identification of cholinergic neuronal genes in P. xanthodes provided candidate molecular markers for study the toxic effects of environmental pollutants on the neuron system of an aquatic predatory insect with ecological importance.

Transport mechanism of presynaptic high-affinity choline uptake by CHT1.

Choline is a vital nutrient and a precursor for the biosynthesis of essential metabolites, including acetylcholine (ACh), that play a central role in fetal development, especially in the brain. In cholinergic neurons, the high-affinity choline transporter (CHT1) provides an extraordinarily efficient reuptake mechanism to reutilize choline derived from intrasynaptical ACh hydrolysis and maintain ACh synthesis in the presynapse. Here, we determined structures of human CHT1 in three discrete states: the outward-facing state bound with the competitive inhibitor hemicholinium-3 (HC-3); the inward-facing occluded state bound with the substrate choline; and the inward-facing apo open state. Our structures and functional characterizations elucidate how the inhibitor and substrate are recognized. Moreover, our findings shed light on conformational changes when transitioning from an outward-facing to an inward-facing state and establish a framework for understanding the transport cycle, which relies on the stabilization of the outward-facing state by a short intracellular helix, IH1.

Sports Vagotonia as a Result of Increased Synthesis of Non-Neuronal Acetylcholine by Cardiomyocytes

Sports Vagotonia as a Result of Increased Synthesis of Non-Neuronal Acetylcholine by Cardiomyocytes

Pros and cons of alternative therapy omega-3 fatty acids during pregnancy and lactation for mental problems

IntroductionFatty acids omega-3 are irreplaceable. They stabilize cell membranes, nerve impulses, homeostasis, immune reactions, the birth process, the psycho-emotional state of the fetus-mother dyad. Correlations between adequate dietary intake of omega-3 and cognitive health have been described in detail. According to the literature, docosahexaenoic acid is associated with the synthesis of serotonin, dopamine, acetylcholine, glutamate, neuroprotective and anti-apoptotic action, has antidepressant effect. Omega-3 makes up 60% of neuronal membrane phospholipids. Under clinical aspect,according to publications, fish oil reduces the risk of preterm birth by 44%.Objectives The aim is to study the risks and benefits of using omega-3 during pregnancy and lactation in patients with mental disorders.Methods Comparative analysis of evidence-based scientific publications for the use of omega-3 fatty acids in pregnancy and lactation.Results The body level of omega-3 depends on the quantitative intake from food, as well as gene polymorphism and age. For pregnant and lactating women are recommended 200-300 mg per day or about 300 g per week from food. Deficiency of omega-3 (protectins) affects the processes of myelination, neurogenesis, synaptogenesis, the metabolism of neurotransmitters, cell differentiation, neuronal migration and inflammatory responses.Conclusions There are many probably mechanisms of action of omega-3, namely: Enhances peroxisomal oxidation, reduces the synthesis of triglycerides in the liver; inhibits plasma acyltransfrerase. Omega-3 acts on phospholipids of the cell membranes of the nervous system and retina, their adequate functioning, improve psychomotor development of newborns. It was found the effect of decreasing the levels of cytokines and depressive symptoms, as well the risk of food allergies and depression. In conclusion, in adequate doses, omega-3 fatty acids seems to be useful in deficiencies and for prophylactic purposes in pregnancy and lactation.Keywordsomega- 3 fatty acids, pregnancy, lactation, mental disorders.Disclosure of InterestNone Declared

Non-neuronal cholinergic system in the heart influences its homeostasis and an extra-cardiac site, the blood-brain barrier.

The non-neuronal cholinergic system of the cardiovascular system has recently gained attention because of its origin. The final product of this system is acetylcholine (ACh) not derived from the parasympathetic nervous system but from cardiomyocytes, endothelial cells, and immune cells. Accordingly, it is defined as an ACh synthesis system by non-neuronal cells. This system plays a dispensable role in the heart and cardiomyocytes, which is confirmed by pharmacological and genetic studies using murine models, such as models with the deletion of vesicular ACh transporter gene and modulation of the choline acetyltransferase (ChAT) gene. In these models, this system sustained the physiological function of the heart, prevented the development of cardiac hypertrophy, and negatively regulated the cardiac metabolism and reactive oxygen species production, resulting in sustained cardiac homeostasis. Further, it regulated extra-cardiac organs, as revealed by heart-specific ChAT transgenic (hChAT tg) mice. They showed enhanced functions of the blood-brain barrier (BBB), indicating that the augmented system influences the BBB through the vagus nerve. Therefore, the non-neuronal cardiac cholinergic system indirectly influences brain function. This mini-review summarizes the critical cardiac phenotypes of hChAT tg mice and focuses on the effect of the system on BBB functions. We discuss the possibility that a cholinergic signal or vagus nerve influences the expression of BBB component proteins to consolidate the barrier, leading to the downregulation of inflammatory responses in the brain, and the modulation of cardiac dysfunction-related effects on the brain. This also discusses the possible interventions using the non-neuronal cardiac cholinergic system.

Brian Collier (1940-2024).

Dr. Brian Collier, the former Editor-in-Chief of the Journal of Neurochemistry from 1996 to 2006, passed away January 4th, 2024. Brian's illustrious career spanned the fields of neurochemistry and pharmacology. He published his findings on mechanisms of acetylcholine synthesis and storage in the Journal of Neurochemistry, and his contributions remain landmarks in neurochemical research.

Corneal acetylcholine regulates sensory nerve activity via nicotinic receptors

PurposeSensory nerve terminals are highly distributed in the cornea, and regulate ocular surface sensation and homeostasis in response to various endogenous and exogenous stimuli. However, little is known about mediators regulating the physiological and pathophysiological activities of corneal sensory nerves. The aim of this study was to investigate the presence of cholinergic regulation in sensory nerves in the cornea. MethodsLocalization of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (vAChT) was evaluated using western blotting and immunohistochemical analysis. The synthesis and liberation of acetylcholine from the cornea were assessed using corneal segments pre-incubated with [3H]choline. The responsiveness of corneal neurons and nerves to cholinergic drugs was explored using calcium imaging with primary cultures of trigeminal ganglion neurons and extracellular recording from corneal preparations in guinea pigs. ResultsChAT, but not vAChT, was highly distributed in the corneal epithelium. In corneal segments, [3H] acetylcholine was synthesized from [3H]choline, and was also released in response to electrical stimuli. In cultured corneal neurons, the population sensitive to a transient receptor potential melastatin 8 (TRPM8) agonist exhibited high probability of responding to nicotine in a calcium imaging experiment. The firing frequency of cold-sensitive corneal nerves was increased by the application of nicotine, but diminished by an α4 nicotinic acetylcholine receptor antagonist. ConclusionsThe corneal epithelium can synthesize and release acetylcholine. Corneal acetylcholine can excite sensory nerves via nicotinic receptors containing the α4 subunit. Therefore, corneal acetylcholine may be one of the important regulators of corneal nerve activity arranging ocular surface condition and sensation.

Citiholin u neurologiji i psihijatriji

Citicoline is a supplement-nootropic with potential applications in treating various neurological, psychiatric, and other conditions. There is experimental and clinical evidence of the benefits of citicoline in individuals after stroke, traumatic brain injury, and cognitive decline of various etiologies. Preclinical studies suggest that citicoline has neuroprotective and neurorestorative effects, which can be explained by its antioxidant, anti-inflammatory, and metabolic actions. Citicoline is necessary for the synthesis and stabilization of biological membranes, improves mitochondrial function, and is crucial in the synthesis of acetylcholine and other neurotransmitters in the central nervous system. No specific drugs are available for treating cognitive sequelae of stroke and traumatic brain injury. In experimental and clinical studies, citicoline has shown a safe profile with positive clinical effects on overall cognitive abilities, attention, executive function, and mood. There are also positive results of its use in patients with neurodegenerative diseases, although on a small number of participants. In psychiatry, the beneficial effects of citicoline on depression, negative symptoms of schizophrenia, and substance use disorders are described. This review provides an overview of the mechanisms of action of citicoline and summarizes the published research on its use in neurology and psychiatry.

Greater Omentum: Multifaceted Interactions in Neurological Recovery and Disease Progression.

The greater omentum, a unique anatomical structure composed of adipocytes, loose connective tissue, and a dense vascular network. Plays a pivotal role beyond its traditional understanding. It houses specialized immunological units known as 'Milky spots,' making it a key player in immune response. Moreover, the omentum's capacity to enhance tissue perfusion, absorb edema fluid, boost acetylcholine synthesis, and foster neuron repair have rendered it a topic of interest in the context of various diseases, especially neurological disorders. This review provides a comprehensive overview of the intricate anatomy and histology of the greater omentum, casting light on its multifaceted functions and its associations with a spectrum of diseases. With a specific focus on neurological ailments, we delineate the intricate relationship that the omentum shares with other pathologies like stroke and we underly its contribution to serving as a therapeutic agent in neurological disorders. By deciphering the underlying mechanisms and emphasizing areas that demand further investigation. This review aims to spark renewed interest and pave the way for comprehensive studies exploring the greater omentum's potential in neurology and broader medicine overall. Given these diverse interactions that yet remain elusive, we must investigate and understand the nuanced relationship between the greater omentum and pathologies, especially its role in stroke's pathophysiology and therapeutic interventions so as to enhance patient care.