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A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

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Neural Regeneration Research 2024年第2期19卷 324-330页

作者： Xi Chen Yuhu Zhang Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Shantou University Medical College ShantouGuangdong ProvinceChina

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

关键词： anterior brain system cerebellum cholinergic cognitive impairment dopaminergic dual syndrome hypothesis neuroimage neurotransmitter Parkinson’s disease posterior brain system therapeutic targets

Perioperative cardiac risks in myasthenia gravis

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World Journal of Clinical Cases 2024年第13期12卷 2147-2150页

作者： Deb Sanjay Nag Abhishek Chatterjee Pratap Rudra Mahanty Merina Sam Murari Kumar Bharadwaj Department of Anaesthesiology Tata Main HospitalJamshedpur 831001India Department of Anaesthesiology Manipal Tata Medical CollegeJamshedpur 831017India

Myasthenia gravis(MG)is an autoimmune disorder that affects the neuromuscular junction.The primary pathology in MG involves the presence of autoantibodies to acetylcholine receptors(AChRs),which results in qualitative and quantitative reductions in the availability of functional AChRs.Cardiac muscles are also affected,resulting in various perioperative cardiac complications.Antistriational antibodies are commonly reported in MG cases with cardiac involvement.In the presence of thymoma,the prevalence of cardiac manifestations in patients with MG increases to approximately 10%-15%.Cardiac involvement in MG may range from asymptomatic electrocardiogram changes to ventricular tachycardia,myocarditis,conduction disorders,heart failure,and sudden death.Increased incidence of atrial fibrillation,ventricular and supraventricular extra systoles,and prolonged QTc have also been reported in patients with MG.Clinicians should consider the evaluation of autonomic dysfunction and risk of cardiovascular disease in patients with MG.

关键词： Myasthenia Gravis Perioperative period Receptors cholinergic Anesthesia

Mesenchymal stromal cells alleviate acute respiratory distress syndrome through the cholinergic anti-inflammatory pathway

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3884-3897页

作者： Xiaoran Zhang Xuxia Wei Yiwen Deng Xiaofeng Yuan Jiahao Shi Weijun Huang Jing Huang Xiaoyong Chen Shuwei Zheng Jieying Chen Keyu Chen Ruiming Xu Hongmiao Wang Weiqiang Li Shiyue Li Huimin Yi Andy Peng Xiang Department of Surgical Intensive Care The Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510630China Center for Stem Cell Biology and Tissue Engineering Key Laboratory for Stem Cells and Tissue EngineeringMinistry of EducationSun Yat-Sen UniversityGuangzhouGuangdong 510080China National-Local Joint Engineering Research Center for Stem Cells and Regenerative Medicine Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Department of General Intensive Care Unit Lingnan HospitalThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510530China Department of Anesthesiology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China State Key Laboratory of Respiratory Disease and National Clinical Research Center for Respiratory Disease the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouGuangdong 510120China

Mesenchymal stromal cells(MSCs)have been considered a promising alternative for treatment of acute respiratory distress syndrome(ARDS).However,there is significant heterogeneity in their therapeutic efficacy,largely owing to the incomplete understanding of the mechanisms underlying the therapeutic activities of MSCs.Here,we hypothesize that the cholinergic antiinflammatory pathway(CAP),which is recognized as a neuroimmunological pathway,may be involved in the therapeutic mechanisms by which MSCs mitigate ARDS.Using lipopolysaccharide(LPS)and bacterial lung inflammation models,we found that inflammatory cell infiltration and Evans blue leakage were reduced and that the expression levels of choline acetyltransferase(ChAT)and vesicular acetylcholine transporter(VAChT)in lung tissue were significantly increased 6 hours after MSC infusion.When the vagus nerve was blocked orα7 nicotinic acetylcholine(ACh)receptor(α7nAChR)-knockout mice were used,the therapeutic effects of MSCs were significantly reduced,suggesting that the CAP may play an important role in the effects of MSCs in ARDS treatment.Our results further showed that MSC-derived prostaglandin E2(PGE2)likely promoted ACh synthesis and release.Additionally,based on the efficacy of nAChR andα7nAChR agonists,we found that lobeline,the nicotinic cholinergic receptor excitation stimulant,may attenuate pulmonary inflammation and alleviate respiratory symptoms of ARDS patients in a clinical study(ChiCTR2100047403).In summary,we reveal a previously unrecognized MSC-mediated mechanism of CAP activation as the means by which MSCs alleviate ARDS-like syndrome,providing insight into the clinical translation of MSCs or CAP-related strategies for the treatment of patients with ARDS.

关键词： distress cholinergic inflammation

Neurotrophin receptors,gamma-secretase inhibitors,and neurodegeneration of basal forebrain cholinergic neurons

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Neural Regeneration Research 2022年第7期17卷 1493-1494页

作者： Marçal Vilar Instituto de Biomedicina de València del CSIC ValènciaSpain

The amyloid hypothesis of Alzhemer’s disease(AD)postulates that the generation of amyloid-beta(Aβ)peptide from the amyloid precursor protein(APP)by the action of theγ-secretase complex is one of the principal causes of AD.This idea is supported by the identification of several hereditary mutations in the APP gene or in the PSEN1 and PSEN2 genes that encode Presenilin-1 and Presenilin-2.

关键词： amyloid Aβ cholinergic

Emerging significance of butyrylcholinesterase

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World Journal of Experimental Medicine 2024年第1期14卷 33-43页

作者： Gumpeny R Sridhar Lakshmi Gumpeny Department of Endocrinology and Diabetes Endocrine and Diabetes CentreVisakhapatnam 530002Andhra PradeshIndia Department of Internal Medicine Gayatri Vidya Parishad Institute of Healthcare and Medical TechnologyVisakhapatnam 530048Andhra PradeshIndia

Butyrylcholinesterase(BChE;EC 3.***.1.8),an enzyme structurally related to acetylcholinesterase,is widely distributed in the human body.It plays a role in the detoxification of chemicals such as succinylcholine,a muscle relaxant used in anesthetic practice.BChE is well-known due to variant forms of the enzyme with little or no hydrolytic activity which exist in some endogamous communities and result in prolonged apnea following the administration of succinylcholine.Its other functions include the ability to hydrolyze acetylcholine,the cholinergic neurotransmitter in the brain,when its primary hydrolytic enzyme,acetylcholinesterase,is absent.To assess its potential roles,BChE was studied in relation to insulin resistance,type 2 diabetes mellitus,cognition,hepatic disorders,cardiovascular and cerebrovascular diseases,and inflammatory conditions.Individuals who lack the enzyme activity of BChE are otherwise healthy,until they are given drugs hydrolyzed by this enzyme.Therefore,BChE is a candidate for the study of loss-of-function mutations in humans.Studying individuals with variant forms of BChE can provide insights into whether they are protected against metabolic diseases.The potential utility of the enzyme as a biomarker for Alzheimer’s disease and the response to its drug treatment can also be assessed.

关键词： Esterase Acetylcholinesterase Variant cholinergic Metabolic syndrome Cognition Knockout model

WHOLE-CELL CLAMP STUDY OF XENOPUS EMBRYONIC cholinergic NEURONS

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Science China Chemistry 1989年第2期32卷 148-154页

作者：谢佐平王堤竺煜杰 Department of Biology Tsinghua University Beijing

Whole-cell clamped myoballs are placed into direct visible contact with the growth cones of isolated neurons in embryonic Xenopus culture to serve as probe of acetylchollne (AcCHo) release in order to determine whether these neurons are cholinergic or not. Using a GQ-seal, whole-cell recording method, the electrophysiological properties of these identified cholinergic neurons are studied. It is found that these embryonic neurons, like adult frog motor neurons, exhibit repetitive firings in a certain embryonic developing stage. A development of repetitive firings is observed simultaneously. Tracing the development of one neuron, we find that the development of repetitive firing is completed at the 48th h after fertilization. Tetrodotoxin (TTX) which blocks Na^+ channels can abolish all firings; and tetraethyl ammonium chloride (TEA), the blocker of K^+ channels, reverses this development, i. e. it makes the repetitive firings disappear again. These data show that the nature of the development of

关键词： whole-cell clamp cholinergic neurous repetitive firings Xenopus embryo.

Mapping the Brain-Wide cholinergic Neurons Projecting to Skeletal Muscle in Mice by High-Throughput Light Sheet Tomography

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Neuroscience Bulletin 2021年第2期37卷 267-270页

作者： Dayu Chen Xiaofeng Cheng Xiong Yang Yongsheng Zhang Zhigang He Qian Wang Guojie Yao Xiuli Liu Shaoqun Zeng Jincao Chen Hongbing Xiang Department of Neurosurgery Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Neurosurgery Central Theater Command General Hospital of the People’s Liberation ArmyWuhan 430070China Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan 430074China Ministry of Education Key Laboratory for Biomedical Photonics School of Engineering SciencesHuazhong University of Science and TechnologyWuhan 430074China Department of Emergency Medicine Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430074China Department of Anesthesiology and Pain Medicine Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Dear Editor,The cholinergic system plays an important role in regulating locomotion and motor functions by modulating neuronal activity[1].However,the anatomical relationships between the brain-wide cholinergic system and skeletal muscles remain unclear.To understand how this system modulates the activity of skeletal muscles,details of the pattern of cholinergic innervation and differences in the innervation of skeletal muscles are necessary.However,classical immunohistochemical methods are unable to test unequivocally whether a mapping exists in the connections from the brain to skeletal muscles.

关键词： skeletal muscles cholinergic

METABOLIC KINETICS OF BRAIN MUSCARINIC cholinergic RECEPTORS IN NORMAL AND HYPOTHYROID MICE

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Nuclear Science and Techniques 1993年第4期4卷 222-229页

作者：胡雅儿易宁育何路明夏宗勤 Shanghai Second Medical University Shanghai 200025 China

A technique for studying in vivo the production rate and turnover rate constant of mouse brain M-receptors was established. A single injection of 25 mg / kg of Benzilylcholine Mustard to living mice resulted in 90 % irreversible block of brain M-receptors. The time course of the receptor density was then monitored by 3H-QNB binding assay and the production rate and turnover rate constant were calculated from the time course curve with a computer program. It was found that in normal mice the turnover rate constant was about 0.035 h-1 (half-life was about 20 h) and the production rate was 30-42 fmol / (h ·mg protein). Parallel experiments revealed a significant slow down of the turnover of brain M-receptors in hypothyroid mice (turnover rate constant was 0.0257±0.0012 h-1 in hypothyroid vs. 0.0356±0.0021 h-1 in normal) while the production rate was not changed significantly. The results suggest that thyroid hormones have a regulatory action on the turnover of brain M-receptors and the elevation of brain M-receptor density together with slow down of the turnover of brain M- receptors is probably one of the important mechanisms relevant to the brain dysfunction in hypothyroidism.

关键词： Hypothyroidism Muscarinic cholinergic receptor Benzilylcholine mustard (BCM) Metabolic kinetics of M-receptor Brain M-receptor

Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway

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China Medical Abstracts(Internal Medicine) 2023年第4期40卷 194-195页

作者：辛娟娟 Instit Acupunct&Moxib Chin Acad Chin Med SciBeijing 100700

Objective To observe the effect of electroacupuncture(EA)at"Neiguan"(PC 6)on myocardial fibrosis in spontaneously hypertensive rats(SHR),and explore preliminarily the mediating role of cholinergic antiinflammatory pathway(CAP)and its downstream nuclear factorκB(NF-κB)signaling pathway.Methods Six 12-week-old WKY male rats were employed as the normal group.

关键词： hypertensive cholinergic rats