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Abstract Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double‐blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane‐based or propofol‐based anesthesia groups. The Mini‐Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholinesterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini‐Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane‐ or propofol‐based general anesthesia did not differ regardless of Mini‐Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane‐based anesthesia has short‐term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration.

In this study, 50 SD adult male mice were used to create an Alzheimer's disease model. The mice's learning and memory abilities were evaluated using an eight-arm radial maze experiment, and changes in body weight and food intake were noted. This helped to better validate the improvement of Alzheimer's disease caused by pine nut peptide-zinc chelate (Korean pine). For a more thorough investigation, mice's brains were dissected, Endogenous mercaptan antioxidants (enzymes), which are markers of brain tissue, were assessed, and mouse gut flora was analyzed. The findings demonstrated that pine nut peptide-zinc chelate (Korean pine) can improve learning and memory, stop brain aging and damage, and control gut flora in mice. It may exert its effects by ameliorating decreased AChE levels and increased ChAT levels in the central cholinergic system, endogenous thiol antioxidants (enzymes) in the cerebral cortex, and by controlling the bacterial flora in the gut.

Aim: The aim of this study was to assess the influence of adrenomedullary secretion on the plasma glucose, lactate, and free fatty acids (FFAs) during running exercise in rats submitted to intracerebroventricular (i.c.v.) injection of physostigmine (PHY). PHY i.c.v. was used to activate the central cholinergic system. Methods: Wistar rats were divided into sham-saline (sham-SAL), sham-PHY, adrenal medullectomy-SAL, and ADM-PHY groups. The plasma concentrations of glucose, lactate, and FFAs were determined immediately before and after i.c.v. injection of 20 μL of SAL or PHY at rest and during running exercise on a treadmill. Results: The i.c.v. injection of PHY at rest increased plasma glucose in the sham group, but not in the ADM group. An increase in plasma glucose, lactate, and FFAs mobilization from adipose tissue was observed during physical exercise in the sham-SAL group; however, the increase in plasma glucose was greater with i.c.v. PHY. Moreover, the hyperglycemia induced by exercise and PHY in the ADM group were blunted by ADM, whereas FFA mobilization was unaffected. Conclusion: These results indicate that there is a dual metabolic control by which activation of the central cholinergic pathway increases plasma glucose but not FFA during rest and exercise, and that this hyperglycemic response is dependent on adrenomedullary secretion. [ABSTRACT FROM AUTHOR]

Vascular dementia (VaD) is a neurodegenerative disease, with cognitive dysfunction attributable to cerebrovascular factors. At present, it is the second most frequently occurring type of dementia in older adults (after Alzheimer's disease). The underlying etiology of VaD has not been completely elucidated, which limits its management. Currently, there are no approved standard treatments for VaD. The drugs used in VaD are only suitable for symptomatic treatment and cannot prevent or reduce the occurrence and progression of VaD. This review summarizes the current status of pharmacological treatment for VaD, from the perspective of the molecular mechanisms specified in various pathogenic hypotheses, including oxidative stress, the central cholinergic system, neuroinflammation, neuronal apoptosis, and synaptic plasticity. As VaD is a chronic cerebrovascular disease with multifactorial etiology, combined therapy, targeting multiple pathophysiological factors, may be the future trend in VaD. [ABSTRACT FROM AUTHOR]

In this study, 50 SD adult male mice were used to create an Alzheimer's disease model. The mice's learning and memory abilities were evaluated using an eight-arm radial maze experiment, and changes in body weight and food intake were noted. This helped to better validate the improvement of Alzheimer's disease caused by pine nut peptide-zinc chelate (Korean pine). For a more thorough investigation, mice's brains were dissected, Endogenous mercaptan antioxidants (enzymes), which are markers of brain tissue, were assessed, and mouse gut flora was analyzed. The findings demonstrated that pine nut peptide-zinc chelate (Korean pine) can improve learning and memory, stop brain aging and damage, and control gut flora in mice. It may exert its effects by ameliorating decreased AChE levels and increased ChAT levels in the central cholinergic system, endogenous thiol antioxidants (enzymes) in the cerebral cortex, and by controlling the bacterial flora in the gut. [Display omitted] • Pine nut peptide-zinc chelate improves learning, memory, brain health, and gut balance in mice. • Pine nut peptide-zinc chelate treats cholinergic system changes, boosts cerebral antioxidants, and alters gut microbiota. • Pine nut peptide-zinc chelate holds potential for Alzheimer's therapy, requiring deeper mechanistic investigation. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of different duration of sevoflurane anesthesia on the cognitive function and the expression of α7-acetylcholine receptor ( α7-nAchR ) in hippocampal neuron of rats. Methods Ninety-six SD rats were randomly divided into four groups (n = 24) ; the control group (C) which inhaled air, and three other groups which were exposed to 3% sevoflurane for 1 (Sl), 3( S2), and 5h (S3), respectively. All rats were trained 5 days by the orientation navigation experiment before anesthesia, 12 rats in each group were tested by space exploration experiment at 1 and 7 days after anesthesia, and we recorded escape latency, the duration of staying in the target quadrant, the swimming distance in target quadrant, total distance, number of crossing platforms, and calculated the ratio of the duration in the original platform quadrant to the total duration, and the ratio of the distance in the original platform quadrant to the total distance. All rats were executed at 1 and 7 days after anesthesia, the hippocampal tissues were obtained for determination of the protein and mRNA expression of α7-nAchR by Western blotting and real-time fluorescent quantitative PCR, respectively. Results Compared with the group C. the duration of staying in the target quadrant, the ratio of the duration in the o-riginal platform quadrant to the total duration, and the ratio of the distance in the original platform quadrant to the total distance were significantly decreased at 1 and 7 days after anesthesia in the S1, S2, and S3 groups ( all P <0.05 ). Compared with the S1, S2 groups, the distance of swimming in the target quadrant, the duration of staying in the target quadrant, the ratio of the duration in the original platform quadrant to the total duration, and the ratio of the distance in the original plat-form quadrant to the total distance were significantly decreased at 1 day after anesthesia in the S3 group (all P <0. 05 ). Moreover, compared with the group C. the protein and mRNA expression of α7-nAchR was significantly down-regulated at 1 and 7 d after anesthesia in the S1, S2, S3 groups ( P <0. 05 ). In the S1, S2, S3 groups, the expression of α7-nAchR protein and mRNA showed a decreasing trend, but no significant differences in the protein and mRNA expression of α7-nAchR was found (all P >0. 05 ). Conclusion Inhalation of 3% sevoflurane anesthesia for 1.3. and 5 h can lead to cognitive decline in rats, cognitive decline caused by anesthesia for 5 h is more obvious; its mechanism may be related to the down-regulation of a7-nAchR protein and mRNA expression. [ABSTRACT FROM AUTHOR]

Abstract: Background: Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality, which has become a major concern of patients and caregivers. Although POCD occurs mainly in aged patients, it happens at any age. Previous studies demonstrated that anesthesia/surgery had no effects on reference memory of adult mice. However, whether it impairs working memory remains unclear. Working memory deficit would result in many deficits of executive function. We hypothesized that anesthesia/surgery impaired the working memory of adult mice and the central cholinergic system was involved. Method: Tibial fracture internal fixation under the anesthesia of isoflurane was performed in two‐month‐old C57BL/6 mice. Two days later, the spatial reference memory and working memory were measured by a Morris Water Maze (MWM). Donepezil, an inhibitor of acetylcholinesterase (AChE), was administered in another cohort mice for 4 weeks. Then, the working memory was measured by MWM 2 days after anesthesia/surgery. Western blot was used to detect the protein levels of acetylcholine transferase (ChAT), AChE, vesicular acetylcholine transporter (VAChT), and choline transporter (ChT) in the prefrontal cortex (PFC). Results: We found that anesthesia/surgery had no effects on the reference memory, but it impaired the working memory in adult mice. Meanwhile, we also found that the protein level of ChAT in PFC decreased significantly compared with that in control group. Donepezil pretreatment prevented working memory impairment and the decrease of the protein levels of ChAT induced by anesthesia/surgery. Conclusion: These results suggest that anesthesia/surgery leads to working memory deficits in adult mice and central cholinergic system impairment is involved. [ABSTRACT FROM AUTHOR]

The purpose of the current study is to investigate the functional connections between the central histaminergic and cholinergic systems at NTS level in hypotensive condition. Experiments were carried out in male Wistar Albino rats. The hypotension was achieved by withdrawing a total volume of 1.5 ml blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in NTS area to measure extracellular ACh and Ch levels. The hemorrhage produced a severe and long-lasting decrease in mean arterial blood pressure (MAP) and increase in extracellular ACh and Ch levels in NTS. Administration of histamine intracerebroventricularly (i.c.v.) or into the NTS reversed the hemorrhagic hypotension by increasing MAP and heart rate. I.c.v. injection of histamine also caused the additional increase in extracellular ACh and Ch levels. Moreover, central histamine injection augmented intracytoplasmic AChE immunoreactivity in NTS. These changes were completely blocked by histaminergic H1 receptor antagonist chlorpheniramine, but histaminergic H2 receptor blocker ranitidine and histaminergic H3/H4 receptor antagonist thioperamide failed to produce these effects. In conclusion, these findings are interpreted that brain histaminergic H1 receptor activation by central histamine injection may promote cholinergic stimulation in the NTS and subsequently reverses the hypotension. [ABSTRACT FROM AUTHOR]

Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double-blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane-based or propofol-based anesthesia groups. The Mini-Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholinesterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini-Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane- or propofol-based general anesthesia did not differ regardless of Mini-Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane-based anesthesia has short-term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley‐VCH GmbH.)

The central cholinergic system is believed to be involved in the control of many physiological functions and is an important pharmacological target for numerous neurological pathologies. Here, we summarize our recent observations regarding this topic that we obtained by studying genetically modified mice devoid of particular cholinesterase molecular forms. Our results, collected from mice with deficits of functional cholinesterases in the brain, suggest that the increase in the level of acetylcholine (ACh) has an impact on cognition only in the situation when extracellular ACh is low. Furthermore, we confirmed the central control of movement coordination, which could be of importance for the management of motor problems in patients with Parkinson's disease. At last, we provide clear evidence that while the hypothermic effect of the muscarinic agonist oxotremorine is based on a central mechanism, in contrast, the acetylcholinesterase inhibitor donepezil decreases body temperature by its action in the periphery. [ABSTRACT FROM AUTHOR]

Butyrylcholinesterase K (BCHE-K) is associated with increased risk of developing Alzheimer's disease (AD) in apolipoprotein ℇ (APOE4) carriers, while among APOE4 non-carriers BCHE-K appears to be protective. Nonetheless, pure pharmacogenetic reports have provided conflicting results. To provide insights about these controversies, we combined BCHE-K pharmacogenetic observations in AD patients (n = 179) with proteomic and enzymatic analysis of plasma, cerebrospinal fluid (CSF), or both samples. We found that BCHE-K genotype was overrepresented among the AD patients (χ2 = 14.21, p < 0.0001). Plasma BuChE activity was gene dose-dependently 20-50% less among K-carriers (p < 0.001). CSF BuChE activity did not show such robust K-gene dosage-dependency, because K homozygotes (n = 9) had 30-40% less activity compared to both non-carriers (n = 78, p < 0.01) and heterozygotes (n = 42, p < 0.09). CSF ApoE protein expression was also altered by presence of K-allele (p < 0.001, n = 129). Mutually, APOE4 altered phenotypic display of BuChE variants in CSF (p < 0.01, n = 129). In absence of APOE4, CSF BuChE activity was essentially indistinguishable among K-carriers (n = 16) and non-carriers (n = 17, p < 0.8) although the K-carriers had 24-39% less circulating BuChE protein. In contrast in presence of APOE4, the K-carriers (n = 35) had K allele dose-dependently a BuChE phenotype with 14-46% reduced activity compared to K non-carriers (p < 0.001, n = 59), despite an essentially identical BChE concentration in CSF (1 ± 4%, p < 0.8). Pattern of the patients' cognitive performance in MMSE closely resembled the APOE4-derived phenotypic display of BuChE variants. APOE4-dependent outcome of BCHE-K genotype as AD risk factor arises through a differential phenotypic modulation of BuChE. Future pharmacogenetic studies should include assessment of the subjects' true phenotypic display of BuChE. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation and aggregation of amyloid-β peptide and loss of forebrain cholinergic neurons, resulting in progressive loss of memory and irreversible impairment of higher cognitive functions. Several studies have accounted for the close relationship between AD and the central cholinergic system, suggesting that a dysfunction of acetylcholine containing neurons in the brain contributes significantly to the cognitive deficit of individuals with AD. The aim of the present review is to survey current literature on this topic in order to provide a clear understanding of the role of the cholinergic system in the development and neurodegenerative process of AD. The implications for anesthesia are also discussed. This knowledge could be valuable to improve anesthesia performance and patient safety. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the effects of Acori graminei rhizoma (AGR) on learning and memory for the Morris water maze task and on the central cholinergic system of the rats with excitotoxic medial septum (MS) lesion. On the water maze test, the rats were trained to find a platform that was in a fixed position during 6 days and then they received a 60 s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesioning of the MS impaired the performance on the maze test and it caused degeneration of choline acetyltransferase and acetylcholine esterase in the hippocampus, which are markers of the central cholinergic system. Daily administrations of AGR (100 mg kg−1, i.p.) for 21 consecutive days produced reversals of the ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus that was induced by ibotenic acid. These results demonstrated that AGR ameliorated learning and memory deficits through their effects on the central nervous system, and neuroprotection was partly evaluated through the effect of AGR on the cholinergic system. Our studies suggest that AGR can possibly be used as treatment for Alzheimer's disease. [ABSTRACT FROM PUBLISHER]

Abstract: Recently we demonstrated that centrally administrated melittin, a phospholipase A2 (PLA2) activator, caused the pressor effect in normotensive, conscious rats. In the present study, we aimed to determine the cardiovascular effect of peripherally injected melittin and the involvement of the central cholinergic system on these effects in the normotensive conscious rats. For this reason, 250, 500 or 1000μg/kg doses of melittin were injected intraperitoneally to normotensive male Sprague Dawley rats. Melittin produced dose- and time-dependent increases in mean arterial pressure (MAP) and heart rate (HR). Both peripheral (5mg/kg; i.p.) and central (500μg; i.c.v.) pretreatment with indomethacin, nonselective inhibitor of cyclooxygenase (COX) 1 and 2, totally abolished cardiovascular effect of melittin. Intraperitoneal (i.p.) pretreatment with propranolol, a nonselective β-adrenergic receptor blocker, completely abolished the tachycardic response to melittin. Also, the pressor effect of melittin was partially attenuated in these rats. In order to test the mediation of the central cholinergic system on the pressor and tachycardic effects of melittin, the rats were pretreated with atropine sulfate (10μg; i.c.v.), a cholinergic nonselective muscarinic receptor antagonist, mecamylamine (50μg; i.c.v.), a cholinergic nonselective nicotinic receptor antagonist, methyllycaconitine (10μg; i.c.v.) or α-bungarotoxin (10μg; i.c.v.), selective antagonists of α7 subtype nicotinic acetylcholine receptors (α7nAChRs) 15min prior to melittin (500μg/kg; i.p.) injection. Pretreatment with mecamylamine, methyllycaconitine or α-bungarotoxin partially diminished the pressor and tachycardic response to melittin in the normotensive conscious rats whereas pretreatment with atropine sulfate had no effect. In conclusion, our data demonstrate that peripherally administered melittin exerts a clear pressor and tachycardic effect by activating COX pathway. The activation of central cholinergic nicotinic receptors, predominantly α7nAChRs, appears to be involved in the pressor and tachycardic effects of the drug. [Copyright &y& Elsevier]

Abstract: Recently we demonstrated that centrally administrated melittin, a phospholipase A2 (PLA2) activator, caused pressor and bradycardic effect in the normotensive conscious rats. In the current study we aimed to determine the mediation of central cholinergic system in the pressor and bradycardic effect of centrally administrated melittin. Studies were performed in normotensive male Sprague–Dawley rats. 1.5, 3.0 or 6.0μg/5.0μl doses of melittin were injected intracerebroventricularly (i.c.v.). Melittin caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR). In order to test the mediation of central cholinergic system on the pressor and bradycardic effect of melittin, the rats were pretreated with mecamylamine (50μg; i.c.v.), cholinergic nonselective nicotinic receptor antagonist, atropine sulfate (10μg; i.c.v.), a cholinergic nonselective muscarinic receptor antagonist, hemicholinium-3 (20μg; i.c.v.), a high affinity neuronal choline uptake inhibitor, methyllycaconitine (10 and 25μg; i.c.v.) or α-bungarotoxin (10 and 25μg; i.c.v.), selective antagonists of α-7 subtype nicotinic acetylcholine receptors (α7nAChRs), 15min prior to melittin (3.0μg) injection. Pretreatment with mecamylamine, hemicholinium-3, methyllycaconitine or α-bungarotoxin partially attenuated the pressor and bradicardia effect of elicited by melittin in the normotensive conscious rats whereas pretreatment with atropine had no effect. In conclusion, i.c.v. administration of melittin increases MAP and decreases HR in conscious rats. The activation of central nicotinic cholinergic receptors, predominantly α7nAChRs, partially acts as a mediator in the pressor responses to i.c.v. injection of melittin in the normotensive conscious rats. Moreover, decreased uptake of choline to the cholinergic terminals may consider that melittin activates central choline and acetylcholine release, as well. [Copyright &y& Elsevier]

Central cholinergic systems are involved in a plethora of brain functions and are severely and selectively damaged in neurodegenerative diseases such as Alzheimer’s disease and dementia with Lewy bodies. Cholinergic dysfunction is treated with inhibitors of acetylcholinesterase (AChE) while the role of butyrylcholinesterase (BChE) for brain cholinergic function is unclear. We have used in vivo microdialysis to investigate the regulation of hippocampal acetylcholine (ACh) levels in mice that are devoid of AChE (AChE-/- mice). Extracellular ACh levels in the hippocampus were 60-fold elevated in AChE-/- mice compared with wild-type (AChE+/+) animals. In AChE-/- mice, calcium-free conditions reduced hippocampal ACh levels by 50%, and infusion of tetrodotoxin by more than 90%, indicating continuous ACh release. Infusion of a selective AChE inhibitor (BW284c51) caused a dose-dependent, up to 16-fold increase of extracellular ACh levels in AChE+/+ mice but did not change ACh levels in AChE-/- mice. In contrast, infusion of a selective inhibitor of BChE (bambuterol) caused up to fivefold elevation of ACh levels in AChE-/- mice, but was without effect in AChE+/+ animals. These results were corroborated with two other specific inhibitors of AChE and BChE, tolserine and bis-norcymserine, respectively. We conclude that lack of AChE causes dramatically increased levels of extracellular ACh in the brain. Importantly, in the absence of AChE, the levels of extracellular ACh in the brain are controlled by the activity of BChE. These results point to a potential usefulness of BChE inhibitors in the treatment of central cholinergic dysfunction in which brain AChE activity is typically reduced. [ABSTRACT FROM AUTHOR]

Abstract: The antinociceptive effect of (+)-matrine was examined in mice by writhing, tail-pressure and hot-plate tests. (+)-Matrine (5, 10 and 20 mg/kg s.c.) produced antinociception in a dose-dependent manner. In hot-plate test, the antinociception produced by (+)-matrine (10 mg/kg s.c.) was attenuated by muscarinic receptor antagonists atropine (5 mg/kg i.p.) and pirenzepine (0.1 μg/mouse i.c.v.) and acetylcholine depletor hemicholinium-3 (HC-3) (1 μg/mouse i.c.v.), but not by opioid receptor antagonist naloxone (2 mg/kg i.p.), dopamine D2 receptor agonist (−)-quinpirole (0.1 mg/kg i.p.) or catecholamine depletor reserpine (2.5 mg/kg i.p.). Radioligand binding assay demonstrated that (+)-matrine had no affinity for μ-, κ- or δ-opioid receptors in a wide concentration range (1×10−11–1×10−3 M). The results suggest that (+)-matrine exerts its antinociceptive effect through multiple mechanism(s) such as increasing cholinergic activation in the CNS rather than acting on opioid receptors directly. [Copyright &y& Elsevier]

The antinociceptive activity of donepezil, a novel cholinesterase inhibitor, was investigated in the mouse hot plate test. Donepezil (5 to 10 mg kg- 1 i.p.) induced a dose-dependent antinociception that reached its maximum effect 15 minutes after injection. Donepezil antinociception was prevented by the antimuscarinic drug scopolamine. At analgesic doses, donepezil did not alter gross animal behavior. These results indicate that donepezil is endowed by muscarinic antinociceptive properties, suggesting this compound as a potential therapeutic approach for the treatment of painful pathologies. Therefore, we investigated donepezil's effect in migraine. Donepezil (5 mg per os, evening assumption) was effective as a prophylatic agent in patients suffering from migraine with or without aura by reducing the number of hours with pain, the number of attacks, and the severity of the pain attack. The efficacy of donepezil was compared with that of the β-blocker propranolol (40 mg bid per os), showing higher activity. Response rates of a large-sized open study devoid of entry criteria regarding migraine subtypes suggest the drug as an excellent prophylactic compound for migraine in general practice. Clinical results also indicate that the activation of the cholinergic system can represent a novel prophylactic approach to migraine. [ABSTRACT FROM AUTHOR]

Using a 100-point Todd scale, we examined the level of neurological deficiency in male albino rats subjected to dosed experimental traumatic brain injury (TBI). In one of the three experimental groups with TBI, animals were not subjected to additional influences; in another group, the central cholinergic system (CChS) was activated by introduction of a central-action cholinomimetic, choline alfoscerate (Gliatilin); in the third group, the activity of the above system was suppressed by a cholinoblocker, biperiden (Akineton). In rats with TBI, the level of neurological deficiency progressively increased; in this group, the estimates at 3 and 72 h after TBI induction corresponded to 474 and 950% of the respective values in intact animals. Blocking of the cholinergic system additionally aggravated manifestations of neurological deficiency, especially within earlier time intervals after TBI (3 and 24 h). Pharmacological activation of the CChS significantly smoothed manifestations of neurological disorders (several times, as compared with those in the TBI group with no additional influences). [ABSTRACT FROM AUTHOR]

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Cyclosporine A (CsA) is the major immunosuppressive drug used for organ and neural transplantation and the therapy of selected autoimmune diseases. We investigated the effect of CsA on the activity of acetylcholinesterase (AChE) in the frontal cortex, hippocampus, septum, and basal ganglia. AChE was determined spectrophotometrically with acetylthiocholine as substrate and 5,5-bis-2-nitrobenzoic acid as chromogen. CsA was administered in single doses of 20 or 45 mg/kg perorally; in the case of the higher dose we also performed a repeated administration of CsA in three consecutive doses separated by 24 h intervals. Both lower and higher doses of CsA decreased AChE activity in the frontal cortex and hippocampus to practically the same extent. On the contrary, AChE activity was more diminished in the case of the higher dose of CsA used in the septum and basal ganglia. Repeated administration of the higher dose of CsA did not lead, with the exception of the hippocampus, to a further decrease in AChE activity in the brain structures observed. These findings contribute to rare evidence concerning the interaction of CsA and the cholinergic system in the brain. [Copyright &y& Elsevier]

Vascular dementia (VaD) is a neurodegenerative disease, with cognitive dysfunction attributable to cerebrovascular factors. At present, it is the second most frequently occurring type of dementia in older adults (after Alzheimer's disease). The underlying etiology of VaD has not been completely elucidated, which limits its management. Currently, there are no approved standard treatments for VaD. The drugs used in VaD are only suitable for symptomatic treatment and cannot prevent or reduce the occurrence and progression of VaD. This review summarizes the current status of pharmacological treatment for VaD, from the perspective of the molecular mechanisms specified in various pathogenic hypotheses, including oxidative stress, the central cholinergic system, neuroinflammation, neuronal apoptosis, and synaptic plasticity. As VaD is a chronic cerebrovascular disease with multifactorial etiology, combined therapy, targeting multiple pathophysiological factors, may be the future trend in VaD., Competing Interests: Declaration of interest The authors declare no conflict of interest., (copyright: © 2021 Kuang et al.)

In order to select which action should be taken, an animal must weigh the costs and benefits of possible outcomes associate with each action. Such decisions, called cost-benefit decisions, likely involve several cognitive processes (including memory) and a vast neural circuitry. Rodent models have allowed research to begin to probe the neural basis of three forms of cost-benefit decision making: effort-, delay-, and risk-based decision making. In this review, we detail the current understanding of the functional circuits that subserve each form of decision making. We highlight the extensive literature by detailing the ability of dopamine to influence decisions by modulating structures within these circuits. Since acetylcholine projects to all of the same important structures, we propose several ways in which the cholinergic system may play a local modulatory role that will allow it to shape these behaviors. A greater understanding of the contribution of the cholinergic system to cost-benefit decisions will permit us to better link the decision and memory processes, and this will help us to better understand and/or treat individuals with deficits in a number of higher cognitive functions including decision making, learning, memory, and language., (© 2014 Elsevier Inc. All rights reserved.)