The blood serum acetylcholinesterase levels pre- and post-resection in patients with Hirschsprung’s disease

Objective Alzheimer’s disease (AD) occurs in approximately 10% to 30% of individuals aged 65 or older worldwide. Novel therapeutic agents therefore need to be discovered in addition to traditional medications. Nimodipine appears to possess the potential to reverse cognitive impairment-induced dysfunction in learning and memory through its regulatory effect on the brain-derived neurotrophic factor (BDNF), acetylcholine (Ach), and acetylcholinesterase (AChE) pathway in the hippocampus and prefrontal cortex. Methods Twenty-four male Sprague Dawley rats weighing 380 ± 10 g were used for behavioral and biochemical analyses. These were randomly and equally assigned into one of three groups. Group 1 received saline solution alone via the intraperitoneal (i.p) route, and Group 2 received 1 mg/kg/day i.p. scopolamine once a day for three weeks for induction of learning and memory impairments. In Group 3, 10 mg/kg/day nimodipine was prepared in tap water and administered orally every day for three weeks, followed after 30 min by 1 mg/kg/day scopolamine i.p. Behavior was evaluated using the Morris Water Maze test. BDNF, ACh, and AChE levels were determined using the ELISA test in line with the manufacturer’s instructions. Results Nimodipine treatment significantly increased the time spent in the target quadrant and the number of entries into the target quadrant compared to the scopolamine group alone. Additionally, BDNF and ACh levels in the hippocampus and prefrontal cortex decreased following 20-day scopolamine administration, while AChE activation increased. Conclusion Nimodipine exhibited potentially beneficial effects by ameliorating cognitive decline following scopolamine administration in the hippocampus and prefrontal cortex.

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by cognitive decline and neuronal damage. Cadmium exposure has been implicated in AD pathogenesis. This study aimed to investigate the potential therapeutic effects of Ebixa (memantine), Ginkgo biloba, and selenium in a cadmium-induced rat model of AD. Adult male Wistar rats were divided into six groups: control, control + Ginkgo-treated, cadmium chloride (CdCl2), CdCl2 + Ebixa-treated, CdCl2 + Ginkgo, and CdCl2 + Ginkgo + Selenium. Behavioral tests, including the Morris water maze and passive avoidance learning, were conducted. Additionally, biochemical analysis of acetylcholine (Ach), choline acetyltransferase (AchT), and acetylcholinesterase (AChE) levels in brain homogenates was performed. Histological sections of the cerebral cortex, cerebellum, and medulla were examined. Apoptotic assessment was conducted using the TUNEL assay. CdCl2 exposure resulted in cognitive deficits, reduced Ach levels, and neuronal damage, mirroring AD-like characteristics. Ebixa treatment improved spatial memory behavior as well as Ach, AchT and AChE levels in the brain. Ginkgo biloba and selenium co-administration increased the number of crossings in the Morris water maze test, suggesting memory preservation. Additionally, Ginkgo biloba exhibited potential cholinergic system protective effects. Histological analysis revealed neuroprotection in the cerebral cortex, cerebellum, and medulla. TUNEL assays demonstrated anti-apoptotic effects of both Ebixa and the combination of Ginkgo and selenium. Ebixa, Ginkgo biloba, and selenium showed promise in mitigating cognitive deficits and preserving neuronal structures in a CdCl2-induced AD manifestation in rats. These findings provide insights into potential therapeutic strategies for AD and warrant further investigation.

Objective To investigate the effect of 17β-estradiol on ketamine-induced long-term cognitive deficits in neonatal rats. Methods 80 SD male rats aged 7 days were randomly divided into group C, V, E, K and K+ E, and 16 per group. Group C was intraperitoneally injected with same volume of saline for three consecutive days, Group V was subcutaneously injected with same volume of sesame oil for three consecutive days, Group E was subcutaneously injected with 600 μg·kg-1 17β-estradiol for three consecutive days, group K was intraperitoneally injected with 75 mg·kg-1 ketamine for three consecutive days, group K+ E was intraperitoneally injected with 75 mg·kg-1 ketamine in combination with 600 μg·kg-1 17β-estradiol injected subcutaneously for three consecutive days. At 2 months of age, learning and memory abilities were tested with the Morris water maze. After Morris water maze test, ten rats from each group were decapitated and the prefrontal cortex (PFC) was isolated to detect acetylcholine esterase(AchE) activity with ELISA assay and to measure acetylcholine(Ach) level by hydroxylammonium chloride method. Results The escape latency ((40.26±2.36)s, (30.25±2.20)s, (21.55±2.42)s) and path length((1019.35±58.13)cm, (811.16±27.58)cm, (598.34±34.74)cm) of group K were more than those of group C on the third, fourth and fifth training days(all P<0.05), while escape latency ((29.46±2.20)s, (24.86±2.14)s, (17.20±1.91)s) and path length((913.90±41.89)cm, (729.42±31.36) cm, (487.64±18.61)cm) of group K+ E were significantly lower than those of group K(all P<0.05). On test day 6, rats were subjected to a probe trial, ratio of time spent in the target quadrant ((24.5±2.7)%) and the number of crossings over previous platform locations(1.9±0.5)in group K were fewer than those of group C (all P<0.05), while ratio of time spent in the target quadrant((42.3±3.0)%) and the number of crossings over previous platform locations(3.5±0.5)of group K+ E were more than those of group K (all P<0.05). The AchE activity((0.69±0.04)U·mg pro-1) in rats PFC of group K was significantly higher than that of group C ((0.52±0.06)U·mg pro-1) (P<0.05). The AchE activity of group K+ E ((0.58±0.12)U·mg pro-1) was lower than that of group K(P<0.05). The Ach level ((2.59±0.34)mg·g-1) in rats PFC of group K was significantly lower than that of group C ((4.35±0.56)mg·g-1)(P<0.05). The Ach level of group K+ E((3.88±0.61)mg·g-1) was higher than that of group K(P<0.05). Conclusions These results indicate that ketamine impairs learning and memory abilities as rat matures, while 17β-estradiol treatment improves these impairments by inhibiting AchE activity and increasing Ach level. Key words: 17β-estradiol; Ketamine; Prefrontal cortex; Morris water maze; Acetylcholine esterase; Acetylcholine

The possible protective effect of Ginger on Alzheimer’s disease induced in rats was investigated. Ninety rats were used as follows: control group, AD protective group using AlCl3, 3rd, 4th, and 5th groups rats were received orally Rivastigmine, Ginger (108 and 216 mg/kg/day) respectively, for two weeks followed by combination of each treatment for another 4 weeks. 6th group is a therapeutic AD group, while 7th, 8th & 9th groups are AD rats treated with the same doses of Rivastigmine and Ginger for 12 weeks. At baseline and after each treatment, behavioral stress tests, Rotarod and T-Maze tests were done. At the end of all experiments rats' brains were dissected and prepared for determination of acetylcholine (Ach), acetycholinesterase (AchE) levels and histopathologic examination. This study indicated that AD-induced rats exhibited reduction in behavior, Rotarod and T-Maze tests, reduction in brain Ach and increase AchE levels. While rats treated with Rivastigmine and Ginger in protective and therapeutic groups exhibited significant improvement in behavior, Rotarod and T-Maze, significant increase in brain Ach and decrease AchE levels. These results were consistent with the histopathological findings and revealed Rivastagmine, and Ginger ameliorates neurodegeneration characters of Alzheimer’s diseases in rats.

Objective To investigate the possible pathogenesis of the cognitive function in unilateral frontal bottom laceration by follow-up study in patients after one month of the onset. Methods MMSE, Loewenstein Occupational Therapy Cognitive Assessment (LOTCA), Montreal Cognitive Assessment (MoCA), Wisconsin Card Sorting Test (WCST) scales were used to evaluate neurocognitie function in 42 patients after one month of onset of unilateral frontal bottom laceration and 45 normal controls. The wave amplitude and the latency of the endogenous composition N2, P3 of P300 were measured at the cognitive potential instrument. Level of AChE was determined by ELISA and active AChE was analyzed by the ration analyses. Stepwise multivariate regression analyzed the correlation of the overall cognitive function and the lever and active of AChE. Results The cognitive test scores in patients were significantly worse than those in normal controls. The ability of recite sentences, fluency of words, reading, understanding language,cognitive transfering decreases in the left frontal bottom laceration patients (Group A, 23 cases), while the ability of attention, action, organization, graphics depicting, abstract epitoming, logical thinking were all seriously impaired in the patients with right frontal bottom laceration (Group B, 19 cases). The latency of the endogenous composition N2, P3 in patients ( Group A: (322. 4 ± 17.0), (410. 1 ± 19.9) ms; Group B:( 308.4 ± 15.6), (385.5 ± 17.4) ms) is more lengthen ( F = 4. 084, P = 0. 018; F = 3.467, P = 0. 038 )than the normal controls ( (268.6 ± 14. 7 ), ( 369. 2 ± 15. 4 ) ms) and the wave amplitude is lower ( F =2. 986 ,P =0. 047 ;F =3. 313 ,P =0. 041 ). The latency of N2 ,P3 in Group A of is more lengthen than Group B, while the wave amplitude is higher. The difference of the active of AChE in patients and control groups had no statistical significance, however, the level of AChE in two groups had statistical significance. The comparison of the active and the total AChE in patients has also not statistical significance. The correlation of the overall cognitive function has the linear regression with the parts of the brain and the level of AChE ( rY1.2 = 0. 584, P = 0. 039; rY2.1 = 0. 726, P = 0. 017 ). The standardized regression coefficients showed the level of AChE has the biggest influence to the overall cognitive function ( |Beta| =0. 3601, rY2.1 =0. 726).Conclusions AChE may be one of the important factors in the cognitive function after frontal bottom laceration. The specific damages of cognitive function in unilateral frontal bottom laceration patients closely relate with the lesion locations in the injured frontal bottom laceration. Key words: Brain injuries; Cognition disorders; Event-related potentials, P300; Cholinesterases

Dietary restriction (DR), as a natural intervention, not only benefits the neuroendocrine system, but also has an antiaging action. Acetylcholinesterase (AChE) is one of the most important bioactive substances and plays a major part in choline changes in the aging process. Thus, we aim to evaluate the effect of DR on AChE in the brains of aging animals. In this study, we synthesize a NIR fluorescent probe BD-AChE for the real-time and in situ monitoring of AChE level changes in living cells and living mice, notably in brains. In situ visualization with BD-AChE verified a decrease in the AchE level in the brains of mice aging models. Evidently, the prepared probe has the excellent capability of measuring AChE variation in the brains of aging mice with DR via NIR fluorescence bioimaging, indicating that long-term DR can effectively affect AChE levels in the brain. The attenuation of AChE level in the brain of aging mice after DR could be helpful in infering the advantageous impact of DR on age-related neurodegenerative disease, as a better treatment alternative in the future.

The exposure of non-target aquatic organisms to sublethal levels of combinations of environmental pollutants may result in synergistic, antagonistic or additive effects. Short-term exposures of planaria to sublethal concentrations of malathion, carbaryl and 2,4-D alone, and in combination, resulted in alterations in both neurobehavior and acetylcholinesterase (AChE) levels. Both interactive and individual effects of the pesticides were concentration dependent. Pesticide mixtures produced varied interactive effects. At very low levels, all pesticide mixtures produced significant (p &amp;lt; 0.01) synergistic responses in the neurobehavior of planaria and resulted in a greater number of responses than predicted additive values. Responses obtained from exposure to low levels of the pesticide mixtures showed a less than additive increase. Malathion and carbaryl exposure resulted in 5–45% decreases in AChE activity. AChE levels increased 6–34% after 2,4-D exposure. Evaluation of planarian neurobehavior responses provided a simple, sensitive method for biomonitoring the interactive sublethal toxicity associated with pesticide mixtures.

Objective: The present study aims to investigate the protective effect of methanol fraction of Morus alba (MEMA) leaves against hydrogen peroxide (H2O2)-induced U87MG cell toxicity and aluminum fluoride (ALF)-induced rat toxicity.&#x0D; Methods: The study was divided into in vitro and in vivo sections. U87MG cell lines were pre-treated with different fractions of MEMA for 20 h and further tested against 1000 ϻM of H2O2. The best fraction from in vitro studies was used to study the protective effects against ALF-induced neurotoxicity. Rats were divided i nto five different groups, and MEMA (200 and 400 mg/kg p.o) was administered for 14 days to the animals with α-tocopherol as the standard drug treatment. Behavioral studies were assessed using Barnes maze. The major biochemical measurements included catalase, superoxide dismutase and glutathione reductase, lipid peroxidation (LPO), and acetylcholinesterase (AchE) levels.&#x0D; Results: In vitro studies indicated MEMA as a potential candidate followed by AQMA and ethyl acetate. The MEMA fraction was able to ameliorate ALF-induced neurotoxicity in the behavioral assessment. The higher antioxidant content in the fraction decreased the LPO levels from 250±4.07 to 115±3.22 as well as elevated the levels of most of the endogenous antioxidant enzyme levels. AchE levels were also decreased to 33.89±0.71 from 38.94±0.64.&#x0D; Conclusion: Although the results obtained indicate that MEMA could significantly suppress oxidative stress-induced central neuronal damage both in vitro and in vivo, further mechanistic studies are required to delineate its neuroprotective pathway.

Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

In order to study possible age-dependent changes in the number of cholinergic binding sites, we have examined alpha-bungarotoxin (ABTX) binding in the ciliary ganglion and iris of the chicken from 3 months after hatching (a.h.) to 5 years of age and have compared it to acetylcholinesterase (AChE) activity and acetylcholine (AChE) levels. In ciliary ganglia the amount of ABTX binding per ganglion increases 16-fold between 3 and 7 months, after which it returns almost to the 3-month level, at 1.3 years. It then remains virtually unchanged to 5 years. A similar pattern is observed in the amount of binding per protein. ACh levels and AChE activity show a different pattern than ABTX binding. In the iris the amount of ABTX binding remains constant between 3 months and 1.3 years and then it increases 1.6-fold up to 3 years. This period is followed by a decrease to 5 years. The amount of ABTX binding per protein which has increased continuously in the iris from the period following hatching up to 7 months, decreases continuously from 7 months to 5 years. In the iris, both ACh levels and AChE activity per protein follow a pattern which is similar to ABTX binding, decreasing from 3 months to 2 years and then remaining relatvely unvaried between 2 and 6-7 years. Our results suggest that a decrease in receptor number begins during early adulthood in the ganglia, whereas this event occurs at a later stage in the iris. However, the total amount of ABTX binding is still relatively high at late stages. These results support our view that the presynaptic component is more affected by the aging process than the postsynaptic component.

BackgroundAlzheimer’s disease (AD) is considered to be a neurodegenerative disorder that is characterized by increased oxidative stress. Medicinal plants, with their antioxidant properties, have been used to cure several human diseases. The aim of the current study was to explore the protective and therapeutic effect of baicalein on AD-induced rats.Materials and methodsSwiss Wistar rats were used in the study. The rats were divided into five groups. Group I: normal control group treated with water; Group II: disease control treated with AlCl3 to induce the mimicking AD for 4 successive weeks (SW); Group III: normal control group treated with baicalein (5 mg/kg) for 2 SW followed by combination of baicalein and AlCl3 for 4 SW; Group IV: normal control group treated with baicalein (10 mg/kg) for 2 SW followed by combination of baicalein and AlCl3 for 4 SW; Group V: normal control group treated with rivastigmine (0.3 mg/kg) for 2 SW followed by combination of rivastigmine and AlCl3 for 4 SW. Moreover, the therapeutic groups are as follows: Group VI: AD disease control treated with AlCl3 for 4 SW and serving as the therapeutic positive group; Group VII: AD disease control + baicalein (5 mg/kg) for 12 SW; Group VIII: AD disease control + baicalein (10 mg/kg) for 12 SW; Group IX: AD disease control + rivastigmine (0.3 mg/kg) for 12 SW. Behavioral test, T-maze, and rotarod test were also performed before and after the treatment. At the end of the experimental study, all the rats were sacrificed and their brains were removed and divided into two portions. The first portion was homogenated for estimating the level of acetylcholinesterase (AchE) and acetylcholine (Ach). Another portion was used for histopathological evaluation.ResultsThe current investigation showed that baicalein significantly reduced the duration of revolving on the rotarod, cage activity, and T-maze activity in a dose-dependent manner compared with the AD control group rats. It also altered the AchE and Ach levels in the brain homogenates. The histopathology study also provides strength to the protective effect of baicalein.ConclusionThe current study showed that baicalein significantly (P<0.05) improved the biochemical and histopathological condition of AD in rats.

This study aimed to investigate the protective effects of herniarin against acrylamide neuro-toxicity. Rats were administered 50 mg/kg of acrylamide (Acr) along with oral doses of herniarin at 50, 100, and 200 mg/kg for 11 days. After treatment, the animals were sacrificed and biochemical markers including superoxide dismutase (SOD), catalase activity, malondialdehyde (MDA), nitric oxide (NO), thiols and acetylcholine esterase (AChE) level were evaluated. Moreover, mRNA expression of neuro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 were measured using qRT-PCR method. As results, Acr increased MDA with subsequent reduction in SOD, catalase, and thiols content. In contrast, administration of herniarin remarkably normalised the antioxidants and decreased lipid peroxidation. Furthermore, it downregulated mRNA expression of TNF-α, IL-1β, and IL-6 (p < 0.001) as well as decreased NO (p < 0.01) and AchE levels (p < 0.001) in the Acr-injured brains. Herniarin ameliorated Acr-induced brain injury via modulating redox hemostasis, cholinergic function, as well as inhibiting neuro-inflammation in rats.

Background: The golden standard of Hirschsprung's disease diagnosis is through a histopathological examination of the aganglionic site. The significance of serum acetylcholinesterase (AChE) immunohistochemistry for diagnosing Hirschsprung's disease has been widely accepted. However, the study of serum AChE levels in Hirschsprung's disease patients is still scarce. We aimed to examine the serum levels of AChE in individuals with Hirschsprung's disease. Methods: An analytical observational study with a cross sectional design was conducted on 29 patients with Hirschsprung's disease. We divided the patients into two groups: 14 in Hirschsprung's disease group and 15 in the control group. Serum AChE level was measured using the enzyme-linked immunosorbent assay (ELISA) method. The optimal cut-off value for detecting Hirschsprung’s disease was determined using the ROC analysis. Results: The prevalence of Hirschsprung was higher in males than in females. The average AChE level in the Hirschsprung group was 95.89 ± 51.11 Units/mL, while the average level of AChE in the control group was 44.45 ± 33.40 Units/mL. The optimal cut-off value was 46.615 Units/mL. We found that this study's sensitivity, specificity, positive predictive value, negative predictive value, and accuracy values ​​were 83.3%, 70.6%, 66.7%, 85.7%, and 75.9%, respectively. There was a significant relationship between serum AChE levels and Hirschsprung's disease (p=0.004). Conclusion: The AChE levels in blood serum can be used as an alternative diagnostic parameter for Hirschsprung's disease. Patients with Hirschsprung's disease had higher serum AChE levels than patients without Hirschsprung's disease.

Galantamine, a weak acetylcholine esterase (AChE) inhibitor and allosteric potentiator of nicotinic ACh receptors (nAChRs), improves apomorphine-induced deficits in prepulse inhibition (PPI), sensory information-processing deficits, via a nAChR-independent mechanism. The present study examined the role of muscarinic ACh receptors (mAChRs) in the effect of galantamine, and studied the mechanism of galantamine-induced increases in prefrontal ACh levels in mice. Apomorphine (1 mg kg(-1)) was administered to male ddY mice (9-10 weeks old) to create a PPI deficit model. Extracellular ACh concentrations in the prefrontal cortex were measured by in vivo microdialysis. Galantamine- and donepezil-mediated improvements in apomorphine-induced PPI deficits were blocked by the preferential M(1) mAChR antagonist telenzepine. The mAChR agonist oxotremorine also improved apomorphine-induced PPI deficits. Galantamine, like donepezil, increased extracellular ACh concentrations in the prefrontal cortex. Galantamine-induced increases in prefrontal ACh levels were partially blocked by the dopamine D(1) receptor antagonist SCH23390, but not by antagonists of mAChRs (telenzepine) and nAChRs (mecamylamine). Galantamine increased dopamine, but not 5-HT, release in the prefrontal cortex. Galantamine improves apomorphine-induced PPI deficits by stimulating mAChRs through increasing brain ACh levels via a dopamine D(1) receptor-dependent mechanism and AChE inhibition.

This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided into four groups. Group 1 (control) received deionized water. Group 2 and 3 received Aluminium (1 mg/kg) and Nickel (0.2 mg/kg) respectively, while Group 4 received Ni and Al mixture HMM three times a week orally for 90 days. Barnes maze tests was performed. Rats were sacrificed under pentobarbital anaesthesia, cerebral cortex and hippocampus were separated, and metal levels were measured using Atomic Absorption Spectroscopy (AAS). Malondialdehyde (MDA), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), Brain Derived Neurotrophic Factor (BDNF), Nerve growth factor NGF, cyclo-oxygenase COX-2 and Acetylcholinesterase (AChE) were assayed using ELISA kits. Ni/Al binary mixture exposed rats showed a shorter latency period (though not significant) of 3.21 ± 1.40 s in comparison to 3.77 ± 1.11 (Ni only) and 3.99 ± 1.16(Al only). Ni/Al mixture gp had the lowest levels of Mg in both the hippocampus and frontal cortex when compared with the individual metals. In the hippocampus Al only exposed rats significantly showed p < 0.05 higher iron and Ca levels in comparison to Ni/Al mixture. Al alone significantly showed p < 0.05 lower levels of Fe but higher Ca than the Ni/Al mixture group. Exposure to Al only showed lower levels of BDNF in comparison to Ni/Al combination, whereas Ni/Al mixture gp had lower levels of NGF in comparison to the individual metals in the hippocampus. In the frontal cortex Ni only, group showed significantly lower BDNF in comparison to Ni/Al mixture whereas the mixture showed significantly lower NGF when compared with Al only group. There were higher levels of COX-2 in the Ni/Al mixture than individual metal treated rats in both hippocampus and frontal cortex. AChE levels in the Ni/Al mixture group was higher than Ni or Al only gps in the hippocampus whereas in the frontal cortex, Ni/Al exposed rats showed significantly lower AChE levels in comparison to Al only group. Ni, Al and Ni/Al mixture exhibited memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus. The BDNF-COX-2 AChE signalling pathway may be involved in the neurotoxicity of Ni and Al.