Increasing Concentrations Of Acetylcholine Research Articles

Esketamine Exposure Impairs Cardiac Development and Function in Zebrafish Larvae.

Esketamine is a widely used intravenous general anesthetic. However, its safety, particularly its effects on the heart, is not fully understood. In this study, we investigated the effects of esketamine exposure on zebrafish embryonic heart development. Zebrafish embryos were exposed to esketamine at concentrations of 1, 10, and 100 mg/L from 48 h post-fertilization (hpf) to 72 hpf. We found that after exposure, zebrafish embryos had an increased hatching rate, decreased heart rate, stroke volume, and cardiac output. When we exposed transgenic zebrafish of the Tg(cmlc2:EGFP) strain to esketamine, we observed ventricular dilation and thickening of atrial walls in developing embryos. Additionally, we further discovered the abnormal expression of genes associated with cardiac development, including nkx2.5, gata4, tbx5, and myh6, calcium signaling pathways, namely ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a3, slc8a4a, and cacna1aa, as well as an increase in acetylcholine concentration. In conclusion, our findings suggest that esketamine may impair zebrafish larvae's cardiac development and function by affecting acetylcholine concentration, resulting in weakened cardiac neural regulation and subsequent effects on cardiac function. The insights garnered from this research advocate for a comprehensive safety assessment of esketamine in clinical applications.

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.

Design of vilazodone-donepezil chimeric derivatives as acetylcholinesterase inhibitors by QSAR, molecular docking and molecular dynamics simulations.

Alzheimer's disease (AD) is a disease that affects the cognitive abilities of older adults, and it is one of the biggest global medical challenges of the 21st century. Acetylcholinesterase (AChE) can increase acetylcholine concentrations and improve cognitive function in patients, and is a potential target to develop small molecule inhibitors for the treatment of Alzheimer's disease (AD). In this study, 29 vilazodone-donepezil chimeric derivatives are systematically studied using 3D-QSAR modeling, and a robust and reliable Topomer CoMFA model was obtained with: q2 = 0.720, r2 = 0.991, F = 287.234, N = 6, and SEE = 0.098. Based on the established model and combined with the ZINC20 database, 33 new compounds with ideal inhibitory activity are successfully designed. Molecular docking and ADMET property prediction also show that these newly designed compounds have a good binding ability to the target protein and can meet the medicinal conditions. Subsequently, four new compounds with good comprehensive ability are selected for molecular dynamics simulation, and the simulation results confirm that the newly designed compounds have a certain degree of reliability and stability. This study provides guidance for vilazodone-donepezil chimeric derivatives as a potential AChE inhibitor and has certain theoretical value.

Highly Diluted Antibodies to eNOS Restore Endothelium Function in Aortic Rings From Hypertensive Rats.

BackgroundNitric oxide (NO) as a vaso- and cardio-protective agent could reduce vasomotor dysfunction in different cardiovascular diseases. One of the current therapeutics targeted at NO availability in the vascular wall are highly diluted antibodies to endothelial NO-synthase (eNOS). This drug has previously shown its endothelium-protective effect and effectiveness in reducing hypertension. Current study was dedicated to evaluate the direct impact of highly diluted antibodies to eNOS on the vessel constriction and dilation ex vivo.MethodsFor that purpose, we used thoracic aortas dissected from spontaneously hypertensive (SHR) rats. Endothelium-dependent relaxation in the presence of highly diluted antibodies to eNOS (1 mL) was examined after phenylephrine-induced pre-constriction of the aorta rings in response to gradually increased acetylcholine concentration (1 nM to 10 µM).ResultsHighly diluted antibodies to eNOS enhanced acetylcholine-induced relaxation in a statistically significant manner. Moreover, it was demonstrated that observed effect was similar to perindopril, a well-known angiotensin-converting-enzyme inhibitor, which works through relaxing and widening blood vessels.ConclusionsOur findings indicate that highly diluted antibodies to eNOS restored impaired endothelium function, as demonstrated by increased relaxation of SHR rats aorta rings. The revealed results suggest beneficial effect of highly diluted antibodies to eNOS to ameliorate hypertension and related diseases.

Identification of cholinergic cells with chemosensory traits in the porcine uterus.

Chemosensory cells are specialized epithelial cells that act as sentinels near body entry sites. The majority of these cells express a cholinergic phenotype and utilize the taste signaling system to monitor the mucosal environment for potentially harmful substances, triggering protective reflexes. We report the identification of cells with a putative chemosensory role in the uterus. Presumptive chemosensory cells were immunoreactive to key components of the taste transduction, including the transient receptor potential channel M5 (TRPM5) and the phospholipase Cβ2 (PLCB2). These cells localized to endometrial glandular and luminal epithelia, while absent from myometrium and perimetrium. Double immunofluorescence revealed co-expression of chemosensory cell markers with the acetylcholine (ACh) synthesizing enzyme, choline acetyltransferase (ChAT). Further, we investigated the regional distribution and expression of chemosensory cells at different stages of the estrous cycle. Uteri were collected postmortem from gilts and stages of the ovarian cycle were determined macroscopically. The uteri were classified into three groups: prepubertal (PB), follicular (FOL), or luteal (LUT). The number of ChAT-immunoreactive cells was increased in the luminal epithelium in the caudal compartment compared to the cranial region of the uterine horn, and at the LUT compared to PB and FOL stages. An increase in ChAT protein abundance in LUT uterine homogenates was noted, although not followed by an increase in ACh content. In summary, our study has identified a hitherto unrecognized cholinergic cell in the uterus that has chemosensory traits and may be involved in a multitude of biological processes.

Comparison of Egg Yolk and Soybean Phospholipids on Hepatic Fatty Acid Profile and Liver Protection in Rats Fed a High-Fructose Diet.

Perturbed lipid metabolism leads to ectopic lipid accumulation in tissues, such as the liver, thereby causing nonalcoholic fatty liver disease (NAFLD) and negatively influencing circulating lipid profile-inducing dyslipidemia. Phospholipids (PLs) with special biological activity are used to treat chronic diseases such as cardiovascular and cerebrovascular disease. PLs derived from egg yolk and soya bean have significant antioxidant and lipid-lowering abilities. This study examined the therapeutic effects of them on hyperlipidemia using a high-fructose-fed rat model; lipid metabolism and anti-inflammatory effects were also analyzed. The results showed that both egg yolk and soya bean phospholipids (EPLs and SPLs) reduced liver weight, hepatic TG, and MDA content as well as serum ALT, AST, TBA, and CRP levels (p < 0.05). The PLs also showed hypolipidemic and anti-inflammatory effects. EPLs and SPLs could inhibit the accumulation of hepatic fatty acids C18:1N9C, C18:0, and C22:6NS of rats fed a high-fat-and-sucrose diet. The intake of EPLs could significantly increase acetylcholine content in the blood and brain tissue. Histological examination showed that PLs intake could ameliorate the damage to liver tissue. This study suggested that EPLs and SPLs had a certain capacity of hypolipidemic and liver protection, and the therapeutic benefits of EPLs tended to be more effective than that of soybean phospholipids.

Alpha-Glycerylphosphorylcholine Increases Motivation in Healthy Volunteers: A Single-Blind, Randomized, Placebo-Controlled Human Study.

Alpha-glycerylphosphorylcholine (αGPC) is a precursor of acetylcholine and can increase acetylcholine concentration in the brain. In addition, αGPC has a role in cholinergic function as well as monoaminergic transmission, including dopaminergic and serotonergic systems. These monoaminergic systems are related to feelings and emotions, including motivation, reward processing, anxiety, and depression. However, the precise effects of αGPC on human feelings and emotions remain to be elucidated. In this study, we investigated changes in the subjective feelings of healthy volunteers using the KOKORO scale before and after administering αGPC. Thirty-nine volunteers participated in a single-blind, placebo-controlled design. Participants completed a KOKORO scale test to quantify self-reported emotional states, three times each day for two weeks preceding treatment and then for a further two weeks while self-administering treatment. αGPC treatment show a tendency to increase motivation during the intervention period. Furthermore, motivation at night was significantly higher in the αGPC group than in the placebo group (p < 0.05). However, αGPC did not show any effects on anxiety. These data suggest that αGPC can be used to increase motivation in healthy individuals.

In Vivo Monitoring of Acetylcholine Release from Nerve Endings in Salivary Gland.

Simple SummaryStimulation of the parasympathetic nervous system results in the secretion of saliva. Previous studies have demonstrated acetylcholine content in homogenate obtained from salivary glands. Acetylcholine in homogenate, however, includes that stored in the cells, as well as that released in the interstitial fluid. The activity of the parasympathetic nervous system is mainly determined by the amount of acetylcholine released. We established an in vivo microdialysis method for monitoring the acetylcholine released from nerve endings in the salivary glands in rats. The results of the present study demonstrated that acetylcholine levels in the dialysate reflect acetylcholine levels in the interstitial fluid of the submandibular gland, and that an increase in the acetylcholine level in the dialysate depends predominantly on the release of acetylcholine from the parasympathetic nerve endings.A microdialysis technique was used to monitor acetylcholine levels in the local interstitial fluid in rat submandibular glands, with the aim of determining parasympathetic nerve activity in vivo. The dialysis probe housed a 10 × 0.22 mm semipermeable membrane (molecular weight cutoffs: 50,000 Da). When the probe was perfused at 2 μL/min in vitro, the mean relative recovery of acetylcholine was 41.7% ± 2.5%. The dialysis probes were implanted in the submandibular glands of anesthetized rats and perfusion with Ringer’s solution, at 2 μL/min, was performed. Acetylcholine concentrations in the dialysate were measured by high-performance liquid chromatography and electrochemical detection. The results revealed the following: (1) that mixing Eserine with Ringer’s solution allowed acetylcholine in the salivary glands to be quantified; (2) that acetylcholine concentrations in the dialysate were highly variable and unstable over the first 120 min after probe implantation, but reached a nearly stable level (4.8 ± 2.7 nM) thereafter in the presence of 100 µM of Eserine; and (3) that electrical stimulation of the chorda tympani nerve, or perfusion with high potassium Ringer’s solution, significantly increased acetylcholine concentrations in the dialysate. These results indicate that the present microdialysis technique offers a powerful tool for detecting changes in parasympathetic activity within the salivary glands.

Complete resection of the gastric antrum decreased incidence and severity of delayed gastric emptying after pancreaticoduodenectomy

BackgroundDelayed gastric emptying (DGE) is the main complication after pancreaticoduodenectomy (PD), but the mechanism is still unclear. The aim of this study was to elucidate the role of complete resection of the gastric antrum in decreasing incidence and severity of DGE after PD. MethodsSprague-Dawley rats were divided into three groups: expanded resection (ER group), complete resection (CR group), and incomplete resection (IR group) of the gastric antrum. The tension (g) of remnant stomach contraction was observed. We analyzed the histological morphology of the gastric wall by different excisional methods after distal gastrectomy. Moreover, patients underwent PD at our department between January 2012 and May 2016 were included in the study. These cases were divided into IR group and CR group of the gastric antrum, and the clinical data were retrospectively analyzed. ResultsThe ex vivo remnant stomachs of CR group exhibited much greater contraction tension than others (P < 0.05). The contraction tension of the remnant stomach increased with increasing acetylcholine concentration, while remained stable at the concentration of 10 × 10−5 mol/L. Furthermore, 174 consecutive patients were included and retrospectively analyzed in the study. The incidence of DGE was significantly lower (3.5% vs. 21.3%, P < 0.01) in CR group than in IR group. In addition, hematoxylin-eosin staining analyses of the gastric wall confirmed that the number of transected circular smooth muscle bundles were higher in IR group than in CR group (8.24 ± 0.65 vs. 3.76 ± 0.70, P < 0.05). ConclusionsThe complete resection of the gastric antrum is associated with decreased incidence and severity of DGE after PD. Gastric electrophysiological and physiopathological disorders caused by damage to gastric smooth muscles might be the mechanism underlying DGE.

Donepezil induces ventricular arrhythmias by delayed repolarisation.

Acetylcholinesterase inhibitors such as donepezil delay the progression of Alzheimer's dementia by increasing acetylcholine concentrations in the central nervous system. However, it is becoming apparent that cholinesterase inhibition by donepezil is not confined to the brain. This is supported by previous case reports of peripheral cholinergic side effects and adverse cardiac arrhythmias such as Torsades de Pointes which are reversible upon cessation of donepezil. The augmented acetylcholine concentrations and IKr inhibition in cardiomyocytes caused by donepezil are believed to mediate this effect.

Transgenerational effects of developmental exposure to chlorpyrifos-oxon in zebrafish (DANIO RERIO)

The organophosphate chlorpyrifos, and its active metabolite chlorpyrifos-oxon (CPO), have been attributed to a number of neurodevelopmental disorders. It is unclear if the adverse effects associated with developmental exposure to the active CPO persist into adulthood and future generations. The goal of this study was to investigate whether CPO-associated changes in embryo-larval zebrafish (ZF) behavior at the F0 5 dpf were manifest throughout the life of the exposed F0, and are inherited by subsequent generations. For this study, embryos were exposed to chlorpyrifos-oxon at the environmentally relevant concentration of 0.01 μg/L and a high concentration of 50 μg/L starting at 4 hpf to 5 dpf, and then raised to F2. There was a significant decrease in distance traveled with 5 dpf F0 ZF exposed to the 50 μg/L CPO, with alterations in noncholinergic genes CFOS and LINGO, and alterations in global DNA methylation. CPO-related behavioral effects were ameliorated by day 21 through the F1 generation. This trend changed with hyperactive behavior, increase acetylcholine concentration in F2 zebrafish that were exposed to 50 μg/L CPO during the F0 development. There was also an increase in AChE activity and hypermethylation in F2 0.01 μg/L exposure larvae, indicating that even low dose exposures can have transgenerational effects. Results from this study demonstrate that early life stage exposures to CPO can lead to epigenetic changes in neurological activity, which may lead to alterations in response to CPO in future generations. Abstract summaryThis study identified a correlation between CPO exposure during F0 development and significant differences in F2 behavioral, AChE activity and neurotransmitter concentration.

Neuroprotective Function of a Novel Hexapeptide QMDDQ from Shrimp via Activation of the PKA/CREB/BNDF Signaling Pathway and Its Structure-Activity Relationship.

This study aimed to evaluate the neuroprotective function of shrimp-derived peptides QMDDQ and KMDDQ. Biochemical results revealed that both peptides exhibited neuroprotective effects by increasing acetylcholine (ACh) content and inhibiting acetylcholinesterase (AChE) activity in PC12 cells; QMDDQ was more active than KMDDQ. COSY-NOESY spectroscopic data showed that the superior neuroprotective function of QMDDQ might be attributed to its N-terminal glutamine as it exhibited an extended spatial conformation, facilitating its interactions with AChE. QMDDQ can promote the basic energy metabolism of cells more than KMDDQ. The peptides showed neuroprotective ability due to the activation of the antiapoptosis and PKA/CREB/BNDF signaling pathway. QMDDQ was selected to investigate its memory-enhancing activity in scopolamine-induced amnesic mice, revealing memory protection in mice, as it improved their performance in the Morris water maze experiment. In addition, QMDDQ increased ACh content (4.98 ± 0.51 μg/mg prot) and decreased AChE activity (4.72 ± 0.11 U/mg prot) in the mouse hippocampus. These data indicate the systemic mechanism through which naturally derived QMDDQ improved neuroprotection and memory ability.

The effects and mechanisms of the action of galangin on spatial memory in rats.

Galangin, a flavonoid compound with acetylcholinesterase inhibitory activity, may improve cognitive functions by enhancing cholinergic transmission. We aimed to investigate the effects of galangin on spatial memory impairment in rats. The effects of galangin (50 and 100 mg/kg) and reference anti-dementia drug donepezil (1mg/kg) administrations were examined on memory impairment induced by the muscarinic cholinergic receptor antagonist scopolamine or the nicotinic cholinergic receptor antagonist mecamylamine in the Morris water maze (MWM) test. Hippocampal acetylcholine concentrations were also determined. Galangin 50 and 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in scopolamine-treated rats. Galangin 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in mecamylamine-treated rats. The effects of galangin in the MWM were comparable with donepezil. Scopolamine and mecamylamine decreased acetylcholine concentrations, whereas galangin both alone and with mecamylamine or scopolamine administration increased acetylcholine concentrations. Galangin improved memory impairment comparable to donepezil and nicotinic and muscarinic receptors may be involved in this effect. Galangin may be considered as a promising flavonoid in the prevention and treatment of memory impairment in Alzheimer's disease and other dementias (Fig. 7,Ref. 37).

Effects of vitamin D3 supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial

Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy and independency in the elderly.1 Currently, no effective pharmacological interventions change the onset or progression of AD.2...

Design and Development of Resveratrol NLCs and their Role in Synaptic Transmission of Acetylcholine in C. elegans Model

Background: The damage of synapses and neurons leads to the cognitive impairment and this is the root cause of progression of Alzheimer’s disease. The nematode Caenorhabditis elegans is widely used as an in vivo model to study the synaptic transmission because of the relatively modest worm nervous system, which is like mammals. Objective: The aim of this work is to assess the effectiveness of resveratrol-loaded nanostructured lipid carrier for the management of Alzheimer's disease. Method: Resveratrol loaded nanostructured lipid carrier (RES-NLC) was prepared by modified solvent emulsification-diffusion technique, using compritol 888ATO (solid lipid), sesame oil (liquid lipid) and tween 80 (surfactant). Results: Formulations were characterized via particle size (155.08±3.28 nm), polydispersity index (PDI) (0.121), and zeta potential (-16.58). The entrapment efficiency was found to be 79.65±2.52% and cumulative percentage drug release was 63.54% up to 8 hours. Anticholinesterase inhibition competence was performed through Aldicarb assay. It was found that surge in the dose of RES-NLC caused an increased worm paralysis, which was credited to the accumulation of acetylcholine in synapses. Quantitative RT-PCR performed showed the effect of formulation on acetylcholinesterase (AChE) AChE 1 and AChE 2 genes. RES-NLC (dose 400 μg/ml) decreased the AChE 1 expression 3.23±0.13 fold whereas AChE 2 expression decreased 3.34±0.14 fold with the same dose. RES-NLC displayed transfer latency and escape latency of 27.50 ± 2.34 and 30.17 ± 2.82. Conclusion: Based on the results, it was concluded that RES-NLC was effective in increasing acetylcholine concentration in synapses and thus in the treatment of Alzheimer's disease. Keywords: Resveratrol, Alzheimer's disease, NLC, C. elegans, aldicarb assay, RT-PCR.

Protective effects of kinetin against aluminum chloride and D-galactose induced cognitive impairment and oxidative damage in mouse.

Increasing evidence indicates that aluminum exposure and oxidative stress play crucial roles in the initiation and development of Alzheimer's disease (AD). Aluminum chloride (AlCl3) and d-galactose (d-gal) combined treatment of mice is considered as an easy and cheap way to obtain an animal model of AD. Kinetin is a plant cytokinin, which is also reported to exert neuro-protective effects in vivo and in vitro. Thus, in this study, neuro-protective effects of kinetin were investigated in an AD model of mice induced by AlCl3 and d-gal. The Morris water maze (MWM) test was performed to directly evaluate neuro-protective effects of kinetin on the memory and spatial learning abilities, while the histopathological changes were examined by hematoxylin and eosin (H & E) staining method. To further investigate mechanisms involved, Al content in cortex and hippocampus was determined. In addition, related detection kits were used to determine acetylcholine (ACh) content and activity of acetylcholinesterase (AChE). Activities of anti-oxidative enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the content of heme oxygenase-1 (HO-1) were also measured. Besides, the content of oxidative damage bio-markers including 8-iso-prostaglandin F (8-iso-PGF), advanced glycation end products (AGEs) and 8-hydroxy-2-deoxyguanosine (8-OHdG) were determined by ELISA kits. Finally, the distribution of beta-amyloid protein 1-42 (Aβ1-42) was detected by immunohistochemistry (IHC), while the expression levels of amyloidogenic proteins including β-amyloid precursor protein (APP), β-secretase, γ-secretase and Aβ1-42 were detected by western blotting (WB) method. Results showed that kinetin improved performance in MWM test, attenuated histopathological changes, reduced Al level in cortex and hippocampus, increased ACh content and decreased AChE activity. In addition, kinetin elevated activities of anti-oxidative enzymes and reduced the levels of oxidative damage biomarkers in AD model of mice. Furthermore, kinetin also increased the content of HO-1, and inhibited the distribution of Aβ1-42 and the expressions of amyloidogenic proteins (APP, β-secretase, γ-secretase and Aβ1-42) in brain tissue of AD mice. Our results indicate that kinetin has neuro-protective effects on the AD model of mice induced by AlCl3 and d-gal, suggesting that kinetin may be a candidate drug for treatment of AD.

Anti-Oxidative Stress Activity Is Essential for Amanita caesarea Mediated Neuroprotection on Glutamate-Induced Apoptotic HT22 Cells and an Alzheimer's Disease Mouse Model.

Amanita caesarea, an edible mushroom found mainly in Asia and southern Europe, has been reported to show good antioxidative activities. In the present study, the neuroprotective effects of A. caesarea aqueous extract (AC) were determined in an l-glutamic acid (l-Glu) induced HT22 cell apoptosis model, and in a d-galactose (d-gal) and AlCl3-developed experimental Alzheimer’s disease (AD) mouse model. In 25 mM of l-Glu-damaged HT22 cells, a 3-h pretreatment with AC strongly improved cell viability, reduced the proportion of apoptotic cells, restored mitochondrial function, inhibited the over-production of intracellular reactive oxygen species (ROS) and Ca2+, and suppressed the high expression levels of cleaved-caspase-3, calpain 1, apoptosis-inducing factor (AIF) and Bax. Compared with HT22 exposed only to l-Glu cells, AC enhanced the phosphorylation activities of protein kinase B (Akt) and the mammalian target of rapamycin (mTOR), and suppressed the phosphorylation activities of phosphatase and tensin homolog deleted on chromosome ten (PTEN). In the experimental AD mouse, 28-day AC administration at doses of 250, 500, and 1000 mg/kg/day strongly enhanced vertical movements and locomotor activities, increased the endurance time in the rotarod test, and decreased the escape latency time in the Morris water maze test. AC also alleviated the deposition of amyloid beta (Aβ) in the brain and improved the central cholinergic system function, as indicated by an increase acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations and a reduction in acetylcholine esterase (AchE) levels. Moreover, AC reduced ROS levels and enhanced superoxide dismutase (SOD) levels in the brain of experimental AD mice. Taken together, our data provide experimental evidence that A. caesarea may serve as potential food for treating or preventing neurodegenerative diseases.

Acetylcholinesterase inhibition by medicinal plants: A Review

Acetylcholinesterase (AChE), the predominant cholinesterase in the brain, hydrolyzes ACh to choline and acetate, thereby terminating the effect of this neurotransmitter at cholinergic synapses. Therefore, AChE is the target of cholinesterase inhibitors used for addressing the cholinergic deficit in Alzheimer’s disease (AD) patients. Despite decades of research and advances in our understanding of its aetiology and pathogenesis, current pharmacotherapeutic options for AD are still very limited and represent an area of need that is currently unmet. The leading AD therapeutics involves AChE inhibitors, resulting in increased acetylcholine concentrations in the synaptic cleft and enhanced cholinergic transmission. Compounds showing an AChE inhibitory effect are also used for the treatment of senile dementia, myastenia gravis, Parkinson’s disease and ataxia. Taking into account that the inhibition of AChE has been one of the most used strategies for treating AD and that existing drugs are effective only against mild to moderate type of disease while presenting considerable side effects, the search for new sources of effective and selective anti acetylcholinesterase agents with fewer side effects is imperative. Various plants and phytochemical substances have demonstrated AChE inhibitory activity and thus could be beneficial in the treatment of neurodegenerative disorders such as AD.

Monitoring Enzymatic Reactions in Real Time Using Venturi Easy Ambient Sonic-Spray Ionization Mass Spectrometry.

We developed a technique to monitor spatially confined surface reactions with mass spectrometry under ambient conditions, without the need for voltage or organic solvents. Fused-silica capillaries immersed in an aqueous solution, positioned in close proximity to each other and the functionalized surface, created a laminar flow junction with a resulting reaction volume of ∼5 pL. The setup was operated with a syringe pump, delivering reagents to the surface through a fused-silica capillary. The other fused-silica capillary was connected to a Venturi easy ambient sonic-spray ionization source, sampling the resulting analytes at a slightly higher flow rate compared to the feeding capillary. The combined effects of the inflow and outflow maintains a chemical microenvironment, where the rate of advective transport overcomes diffusion. We show proof-of-concept where acetylcholinesterase was immobilized on an organosiloxane polymer through electrostatic interactions. The hydrolysis of acetylcholine by acetylcholinesterase into choline was monitored in real-time for a range of acetylcholine concentrations, fused-silica capillary geometries, and operating flow rates. Higher reaction rates and conversion yields were observed with increasing acetylcholine concentrations, as would be expected.

Polysaccharides from Flammulina velutipes improve scopolamine-induced impairment of learning and memory of rats

Flammulina velutipes has been reported to be beneficial in learning and memory capabilities, but the mechanisms underlying this remain unclear. In this study, Morris water maze and biochemical analyses of rat brain were used to evaluate the effects of F. velutipes polysaccharides (FVP) on scopolamine-induced learning and memory impairments. Results suggested that FVP significantly decreased the escape latency and total swimming distance of rats in the hidden platform test and increased the numbers of platform crossing and swimming distance of rats in the probe test. Biochemical examinations revealed that FVP significantly elevates SOD and GSH-Px activities, as well as neurotransmitter levels. The increased acetylcholine content owed to the increased acetylcholine acetyltransferase activity and decreased acetylcholinesterase activity. Moreover, learning and memory associated signalling pathways were activated by FVP elevating the expression of connexin 36 and p-CaMK II. These results conclusively proved that FVP is a potent agent against the progression of cognitive impairment.