Allium hookeri Extracts Improve Scopolamine-Induced Cognitive Impairment via Activation of the Cholinergic System and Anti-Neuroinflammation in Mice

Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1β, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aβ and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.

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.

Análise da estrutura eletrônica da tacrina e do neurotransmissor acetilcolina.

Alzheimer's disease (AD) is a more common neurodegenerative process in the elderly population, characterized by a progressive loss of cognitive abilities, such as memory, language skills, disorientation, attention and depression. Cholinergic hypothesis therapy is the most successful approach for the symptomatic treatment of AD. The therapy consists in the use of drugs with inhibitory action against acetylcholinesterase (AChE) to avoid the decrease of acetylcholine concentration in synaptic clefts. Thus, this research aims to carry out the electronic and structural study of tacrina drug compared to the neurotransmitter acetylcholine, through computational calculations based on theoretical chemistry, using PM6 semi-empirical method jointly to DFT and MP2 methods.

Neurotransmitter networks in mouse prefrontal cortex are reconfigured by isoflurane anesthesia

This study quantified eight, small molecule neurotransmitters collected simultaneously from prefrontal cortex of C57BL/6J mouse (n=23) during wakefulness and during isoflurane anesthesia (1.3%). Using isoflurane anesthesia as an independent variable enabled evaluation of the hypothesis that isoflurane anesthesia differentially alters concentrations of multiple neurotransmitters and their interactions. Machine learning was applied to reveal higher order interactions among neurotransmitters. Using a between-subjects design, microdialysis was performed during wakefulness and during anesthesia. Concentrations (nM) of acetylcholine, adenosine, dopamine, GABA, glutamate, histamine, norepinephrine, and serotonin in the dialysis samples are reported (mean ± SD). Relative to wakefulness, acetylcholine concentration was lower during isoflurane anesthesia (1.254 ± 1.118 versus 0.401 ± 0.134, P=0.009), and concentrations of adenosine (29.456 ± 29.756 versus 101.321 ± 38.603, P<0.001), dopamine (0.0578 ± 0.0384 versus 0.113 ± 0.084, P=0.036), and norepinephrine (0.126 ± 0.080 versus 0.219 ± 0.066, P=0.010) were higher during anesthesia. Isoflurane reconfigured neurotransmitter interactions in prefrontal cortex, and the state of isoflurane anesthesia was reliably predicted by prefrontal cortex concentrations of adenosine, norepinephrine, and acetylcholine. A novel finding to emerge from machine learning analyses is that neurotransmitter concentration profiles in mouse prefrontal cortex undergo functional reconfiguration during isoflurane anesthesia. Adenosine, norepinephrine, and acetylcholine showed high feature importance, supporting the interpretation that interactions among these three transmitters may play a key role in modulating levels of cortical and behavioral arousal.

Peculiarities of values of acetylcholine concentration and cholinesterase activity in serum of patients with alcoholic chronic pancreatitis and duodenal ulcer

Introduction. There are a lot of pathogenic factors involved in development of polyetiologic diseases. Acetylcholine (AC) is known as first-order mediator as it plays an important role in development and maintenance of pathological processes. In this article we provide data on AC concentration in blood serum of patients with duodenal ulcer, alcoholic chronic pancreatitis and control group as well as activity of cholinesterase. The aim of this study was to identify a role played by AC in pathological process during disease, which may complicate a course of the disease as a bad prognostic factor. Results and discussion. We divided AC concentration into three types in the control group: low — 0.46–1.0 mmol/l (60% of individuals), moderate — 1.02–1.5 mmol/l (30%) , and high — more than 1.5 mmol/l (10%). Conclusion. We suppose that cholinesterase activity and AC concentration depend on localization of pathological process.

RELAXATION ACTIVITY OF TETANUS (LEEA AEQUATA L.) LEAF ETHANOLIC EXTRACT ON GUINEA PIG ISOLATED TRACHEA

Objective: The aim of this study is to determine the relaxation activity of the ethanolic extract of tetanus leaf (EETL) against contracting isolated guinea pig trachea induced by acetylcholine.Methods: Isolated trachea was equilibrated for 45 min until a stable condition in the Creb’s solution with a temperature of 37°C aerated with carbogen gas (O2:CO2=95%:5%). Test of the relaxation effect conducted after guinea pig trachea contracted with maximum acetylcholine concentration (EC80: 2.0449×10–3 mol) and then a cumulative with concentration of EETL (0.5 mg/mL–4 mg/mL) and concentration of atropine sulfate (6.95×10-6 mg/mL–2.08×10–2 mg/mL).Results: The results showed that EETL could lower the contraction smooth muscle of guinea pig trachea induced by acetylcholine. EETL at a concentration of 3.5 mg/mL had the ability to relax the muscle. It was not significantly different compared to that of atropine sulfate 6.95×10-3 mg/ mL (p>0.005).Conclusion: EETL has a relaxation effect on smooth muscle of guinea pig isolated trachea.

Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress

Background. Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods. Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results. Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion. Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.

Palonosetron attenuates 1,2-dimethyl hydrazine induced preneoplastic colon damage through downregulating acetylcholinesterase expression and up-regulating synaptic acetylcholine concentration

The present study was undertaken to evaluate the effect of palonosetron (PAL) against 1,2-dimethylhydrazine (DMH)-induced colon cancer.