Baseline acetylcholine levels

Nicotine is the principal psychoactive component in tobacco that drives addiction through its action on neuronal nicotinic acetylcholine receptors (nAChR). The nicotinic receptor gene CHRNA5, which encodes the α5 subunit, is associated with nicotine use and dependence. In humans, the CHRNA5 missense variant rs16969968 (G > A) is associated with increased risk for nicotine dependence and other smoking-related phenotypes. In rodents, α5-containing nAChRs in dopamine (DA) neurons within the ventral tegmental area (VTA) powerfully modulate nicotine reward and reinforcement...

BACKGROUND: Cognitive operations including pre-attentive sensory processing are markedly impaired in patients with schizophrenia (SCZ) but evidence significant interindividual heterogeneity, which moderates treatment response with nicotinic acetylcholine receptor (nAChR) agonists. Previous studies in healthy volunteers have shown baseline-dependency effects of the α7 nAChR agonist cytidine 5'-diphosphocholine (CDP-choline) administered alone and in combination with a nicotinic allosteric modulator (galantamine) on auditory deviance detection measured with the mismatch negativity (MMN) event-related potential (ERP)...

Optimization of effort-related choices are impaired in depressive disorders. Acetylcholine (ACh) and dopamine (DA) are linked to depressive disorders and modulation of ACh tone in the ventral tegmental area (VTA) affects mood-related behavioral responses in rats. However, it is unknown if VTA ACh mediates effort-choice behaviors. Using a task of effort-choice, rats can choose to lever press on a fixed-ratio 5 (FR5) schedule for a more preferred food or consume freely available, less preferred food. VTA administration of physostigmine (1 μg, and 2 μg/side), a cholinesterase inhibitor, reduced FR5 responding for the more preferred food while leaving consumption of the less preferred food intact...

The cholinergic system is a critical mediator of cognition in animals. People who smoke cigarettes exhibit cognitive deficits, especially during quit attempts. Few studies jointly examine the cholinergic system and cognition in people while trying to quit smoking. We used positron emission tomography (PET) brain imaging with the β2 -subunit containing nicotinic acetylcholine receptor (β2 *-nAChR) partial agonist radioligand (-)-[18 F]flubatine and the acetylcholinesterase inhibitor physostigmine to jointly examine the cholinergic system, smoking status, and cognition...

BACKGROUND: The oxidized high-density lipoprotein (oxHDL) is a possible marker for cardiovascular diseases. This study investigated the effects of smoking cessation with varenicline (a partial agonist of nicotinic acetylcholine receptors) on the levels of oxHDL in the serum of subjects compared with those of high-density lipoprotein cholesterol (HDL-C). METHODS: Data of 99 nicotine-dependent adult subjects who visited the smoking cessation outpatient services at International University of Health and Welfare Shioya Hospital were reviewed...

INTRODUCTION: Previous studies have explored prediction value of serum metabolites in neoadjuvant chemoradiation therapy (NCRT) response for rectal cancer. To date, limited literature is available for serum metabolome changes dynamically through NCRT. OBJECTIVES: This study aimed to explore temporal change pattern of serum metabolites during NCRT, and potential metabolic biomarkers to predict the pathological response to NCRT in locally advanced rectal cancer (LARC) patients...

AbobotulinumtoxinA (aboBoNT-A, Dysport® [Ipsen, Paris, France]) inhibits acetylcholine release at the neuromuscular junction and may modulate pain signaling in hallux valgus (HV). This randomized study (NCT03569098) included a double-blind phase (aboBoNT-A 300U, 500U or placebo injections into forefoot muscles) and an open-label aboBoNT-A treatment period in participants with an HV diagnosis and no HV surgery. The primary endpoint was change from baseline in numeric pain rating scale (NPRS) score at week 8...

BACKGROUND: Alzheimer's disease (AD) patients frequently present with orthostatic hypotension. This inability to reflexively increase blood pressure on standing is a serious health concern and increases the risk of stroke and cardiovascular diseases. OBJECTIVE: Since there are no clear mechanisms for orthostatic hypotension in human AD, the present study assessed the autonomic changes that could explain this comorbidity in an AD animal model. METHODS: We used the established streptozotocin-induced rat model of AD (STZ-AD), which mimics many hallmark symptoms of sporadic AD in humans...

BACKGROUND AND OBJECTIVES: Conditions such as trauma, burns, sepsis, or acute intoxications have considerable consequences on the endocrine status, causing "sick euthyroid syndrome". Organophosphate exposure may induce an increase in acetylcholine levels, thus altering the thyroid's hormonal status. The present study aims to identify the effects of acetylcholinesterase inhibition on thyroid hormones. MATERIAL AND METHODS: A prospective experimental study was conducted on twenty Wistar rats...

INTRODUCTION: Myasthenia gravis is characterized by fluctuating muscle weakness that improves with rest and worsens with effort or throughout the day. AREAS COVERED: Efgartigimod is a human IgG1-derived Fc fragment modified at five residues to increase its affinity for the neonatal Fc receptor by Abdeg technology. Thus, efgartigimod binds to the neonatal Fc receptor and decreases the levels of IgG, including autoantibodies of this isotype. For acetylcholine receptor (AChR) antibody-positive patients, efgartigimod had a higher proportion of MG-ADL responders than placebo in the first treatment cycle...

BACKGROUND: Recent studies have demonstrated that T cells can induce vasodilation in a choline-acetyltransferase dependent manner, leading to an increase in T cell migration to infected tissues in response to viral infection, but its role in cancer is unclear. Choline acetyltransferase catalyzes the production of acetylcholine from choline and acetyl-CoA, however, acetylcholine is challenging to quantify due to its extremely short half-life while choline is stable. This study aims to correlate serum choline levels in patients with advanced solid tumors receiving pembrolizumab with treatment outcomes...

BACKGROUND: African Americans (AAs) are disproportionately affected by cardiovascular disease (CVD), they are 20% more likely to die from CVD than whites, chronic exposure to inflammation and oxidative stress contributes to CVD. In previous studies, enhancing parasympathetic cholinergic activity has been shown to decrease inflammation. Considering that AAs have decreased parasympathetic activity compared to whites, we hypothesize that stimulating it with a central acetylcholinesterase (AChE) inhibitor, galantamine, would prevent lipid-induced oxidative stress...

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. Cytokines play important roles in facilitating the immune response and augmenting the pathogenic antibody production. The current study aims to sensitively characterize the serum levels of cytokines with very low concentration in generalized MG (gMG). METHODS: Using ultrasensitive single-molecule arrays (SIMOA), we measured serum IL-2, IL-4, IL-5 and IL-12p70 in 228 participants including 152 immunotherapy-naïve anti-acetylcholine receptor (AChR) subtype gMG from Huashan MG registry and 76 age-matched healthy controls...

Rho-related BTB domain-containing protein 1 (RhoBTB1) is associated with blood pressure in GWAS studies, but its function is not well-understood. The level of RhoBTB1 mRNA was decreased in mice treated with angiotensin II (Ang-II) concomitant with hypertension, arterial stiffness, and impaired vasodilation. Here, we tested the hypothesis that restoration of RhoBTB1 would reverse hypertension, arterial stiffness, and improve vasodilation response caused by Ang-II infusion. Genetic complementation of RhoBTB1 in the vasculature was achieved by expressing a smooth muscle-specific, tamoxifen-inducible RhoBTB1 transgene (S-RhoBTB1 mice)...

Obesity, which is a major risk factor for hypertension and cardiovascular disease, abolishes the cardioprotective effects of female sex hormones and predisposes women to hypertension. Although 40% of postmenopausal women are obese and 75% are hypertensive, the mechanisms whereby obesity and menopause interact to elevate blood pressure (BP) remains unknown. Formerly, our laboratory demonstrated that hypertension involves leptin-mediated increases in aldosterone production in obese female mice of reproductive age...

Myocardial infarction causes parasympathetic dysfunction in cardiovascular tissue, where central parasympathetic drive decreases but local acetylcholine levels are unchanged. However, muscarinic acetylcholine receptor M3 (AChM3R) is shown to have mediating effects in cardiac tissue and vasculature, such as regulation of heart rate and vasodilation of coronary arteries. The objective of this study is to determine the association between AChM3R levels in the heart wall and in the coronary vasculature with self-reported disease states from cadaver donor records...

BACKGROUND: The nervous system integrates the immune system in the systemic effort to maintain or restore the organism's homeostasis. Acute bouts of exercise may alter the activity of specific pathways associated with neuroendocrine regulation of the immune system. OBJECTIVE: To examine the acute effects of heavy resistance exercise on biomarkers of neuroendocrine-immune regulation in healthy adults. METHODS: A systematic literature search was conducted using PubMed, Cochrane Controlled Trials Register, Web of Science and SportDiscus with no date restrictions up to March 2021...

Guilingji capsules (GLJC) have been shown to have antiaging effects and improve cognitive function. The aim of this study was to evaluate the clinical efficacy and safety of GLJC for the treatment of vascular mild cognitive impairment (VaMCI). A total of 96 patients with VaMCI (aged 60-85 years) were enrolled in this 24-week, randomized, double-blind, controlled clinical trial. The patients were randomly assigned to a GLJC group ( n  = 48) or a Ginkgo group ( n  = 48). Patients in the GLJC group were treated using GLJC, whereas those in the Ginkgo group received Ginkgo extract tablets...

Contribution of angiotensin (1-7) (Ang1-7) to control of extrarenal and renal function may be modified in diabetes. We investigated effects of Ang1-7 supplementation on blood pressure, renal circulation and intrarenal reactivity (IVR) to vasoactive agents in normoglycaemic (NG) and streptozotocin-diabetic rats (DM). In Sprague Dawley DM and NG rats, three weeks after streptozotocin (60 mg/kg i.p.) or solvent injection, Ang1-7 was administered (400 ng/min) over the next two weeks using subcutaneously implanted osmotic minipumps...

BACKGROUND: Mild cognitive impairment (MCI) is considered an intermediate phase between normal aging and dementia. As the majority of cases of amnestic MCI (aMCI) progress to Alzheimer's disease (AD), it is considered the prodromal stage of AD, and a treatment target for prevention of further cognitive decline. However, no medications have been shown to have symptomatic or preventive benefits in MCI. Kami-guibi-tang (KGT) is a traditional herbal formula used in Korean medicine to treat amnesia, which is reported to increase acetylcholine levels via activation of choline acetyltransferase...