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Role of cholinergic Receptors in Colorectal Cancer: Potential Therapeutic Implications of Vagus Nerve Stimulation?

Journal of Cancer Therapy 2013年第6期4卷 1116-1131页

作者： Marjolaine Pelissier-Rota Michèle Lainé Benjamin Ducarouge Bruno Bonaz Muriel Jacquier-Sarlin Centre de Recherche Inserm U836 Institute of Neurosciences Grenoble France

Inflammatory Bowel Disease (IBD) patients, such as Crohn’s disease or ulcerative colitis suffer from chronic and relapsing intestinal inflammation that favours the development of colitis associated cancer (CAC). This inflammation is initiated by aberrant activations of the innate immune responses associated to intestinal barrier defects. The conventional medical therapies consist to decrease the inflammatory response, which also decrease the risk of colon carcinoma but lead to severe side-effects. Recently, a number of animal studies have demonstrated that innate immune responses are attenuated by stimulation of the efferent arm of vagus nerve (VN) through its neurotransmitter acetylcholine (ACh), that acts on resident macrophages α7 nicotinic receptor (α7 nAChR). ACh also acts as a signalling molecule in epithetlial cells through cholinergic receptors such as nAChR or muscarinic (mAChR) receptors. In the current study, we aimed to extend these findings to CAC prevention by treating human adenocarcinoma cell lines through targeting cholinergic receptors with nicotine (which binds nAChR) and ACh (which binds both cholinergic receptors). Using HT-29 and Caco-2 cell lines, we demonstrated that ACh-induced activation of mAChR results in cell dissociation together with changes in expression and localization of intestinal tight and adherens junction proteins. ACh-induced modulation of cell adhesion proprieties correlates with the acquisition of invasive potential. By contrast, nicotine-mediated activation of nAChR maintains epithelial cell organisation. ACh-released by VN stimulation (VNS) could effectively preserve epithelium integrity thus limiting inflammatory response and tumor development. However, attention should be paid on the nature of the cholinergic receptor solicited. Indeed, regarding to the protective effects of nAChR signalling on epithelial cells, activation of mAChR would worsen the disease and led to increase inflammation. These data have important reper

关键词： Cell Adhesion Colorectal Cancer Tumor Progression cholinergic Receptors Inflammation Vagus Nerve

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The Acoustic Sensorimotor Gating Predicts the Efficiency of Hypoxic Preconditioning. Participation of the cholinergic System in This Phenomenon

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Journal of Biomedical Science and Engineering 2018年第1期11卷 10-25页

作者： Elena I. Zakharova Zinaida I. Storozheva Andrew T. Proshin Mikhail Yu. Monakov Alexander M. Dudchenko Laboratory of General Pathology of Cardiorespiratory System Institute of General Pathology and Pathophysiology Moscow Russia Laboratory of Clinical Neurophysiology National Medical Research Centre for Psychiatry and Narcology Moscow Russia Laboratory of Functional Neurochemistry P.K. Anokhin’ Institute of Normal Physiology Moscow Russia Laboratory of Functional Angioproteomic and Metabolomic Institute of General Pathology and Pathophysiology Moscow Russia

Moderate one-off hypobaric hypoxia (HBH) provokes preconditioning and prolongs the resistance (T, the time before apnoea) to severe hypobaric hypoxia (SHBH). Hypoxic preconditioning has therapeutic potential;however, the efficiency of hypoxic preconditioning varies greatly and the methods for its preliminary evaluation are absent in both animals and humans. This rodent study evaluates the dependence of SHBH resistance, initiated by HBH, on the rate of sensorimotor gating estimated in the model of the acoustic startle prepulse inhibition (PPI). A stable negative correlation was found between PPI and T. Low doses of the α7 nicotinic receptor agonist, PNU-282987 (PNU), and more pronouncedly dimethyl sulfoxide (DMSO) (a PNU solvent), inverted the correlation between PPI and T from negative to positive. The DMSO and PNU effects were reversed at PPIs of 0.36 - 0.40 (36% - 40%). DMSO increased T values by 52.2% ± 9.7% in the region of lower HBH efficiency (PPI ≥ 0.40) and reduced it by 35.2% ± 9.3% in the region of higher HBH efficiency (PPI cholinergic mechanisms was substantiated in both DMSO and PNU influences on HBH. In conclusion, 1) PPI can be used to predict the efficiency of hypoxic preconditioning and to study its mechanisms, 2) two opposite cholinergic PPI-related mechanisms participate in the preconditioning effects of HBH, 3) the sensitivity of rats to DMSO and PNU diverges when the PPI is 0.36 - 0.40, and 4) DMSO can enhance resistance to severe hypoxia in the region of the lower preconditioning efficiency of HBH at PPI ≥ 0.4.

关键词： Hypoxic Preсonditioning PPI cholinergic Mechanisms α7 Nicotinic Receptors

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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 *** Six 12-week-old WKY male rats were employed as the normal group.

关键词： hypertensive cholinergic rats

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Animal model of vascular dementia and its cholinergic mechanism

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Journal of Medical Colleges of PLA(China) 2001年第3期16卷 230-234页

作者：范文辉李露斯刘之荣朱鸿雁陈康宁 Department of Neurology Southwest Hospital Third Military Medical University Chongqing 400038 China

Objective:To establisha modelof vasculardementia(VD)inagingratsandstudyprimarily thecholinergic mechanismof ***:Chronichypoperfusionof cerebralbloodflow(CBF)intheforebrainwasperformed in agingrats withpermanentbilateralcommoncarotidarteriesocclusion(PBCCAO).Thentheratsweretestedwitha *** cerebrovascularsystemwereobservedwithdigitalsubtractionangio-graphy(DSA).The braintissueswerestudiedwithimmunohistochemicalmethodwithcholinergicacetyltransferase(ChAT)as a ***:Thecognitivefunctionof ratswasobviouslyreducedin2monthsafterchroniccerebralhy-poperfusionandbecameworse2monthslater,showinga moremarkeddecreaseof ChATpositiveneuronsandfibersin CA1of thehippocampusas comparedwiththeratsof thecontrol,whichhada significantpositivecorrelationwithmemo-ry ***:Thisratmodelis successfullyestablishedto imitatehumanVD *** thehypomnesiaof VD mightbe theimpairmentof cholinergicneuronsin frontalcortex andhippocampus.

关键词： vascular dementia memory disorders animal model cholinergic acetyltransferase

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NP-3 Effects of Osthole Microemulsion by Nasal Administration on the cholinergic Pathway in AD Mice

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神经药理学报 2018年第4期8卷 101-102页

作者： HOU Xue-qin RONG Cui-ping HAO Ji-fu ZHANG Han-ting Institute of Pharmacology Taishan Medical UniversityShandong271016China Guangxi Key Laboratory of Brain and Cognitive Neuroscience Guilin Medical UniversityGuilinChina Department of Pharmacy Taishan Medical UniversityShandong271016China Departments of Behavioral Medicine&Psychiatry Physiology&Pharmacologyand Neurosciencethe Rockefeller Neurosciences InstituteWest Virginia University Health Sciences CenterMorgantownWV 26506USA

Objectives:Fructus Cnidii is the dry ripe fruit of Cnidium monnieri(L.)Cuss.,which belongs to the umbelliferous *** has long been used in clinic practice and has been found to have pharmacological activity in the central nervous *** is the main active component of Fructus ***,it shows low bioavailability,fast distribution and elimination,and low concentration in the brain when given *** this study,we aimed to develop a new dosage form to increase the osthole concentration in the brain and enhance its pharmacological effects in the central nervous system through reducing the dosage while improving the stability and ***,microemulsion containing osthole was prepared and the effects of osthole microemulsion were examined in the mouse model of Alzheimer’s disease(AD).Methods:On the basis of pseudo-ternary phase diagram,microemulsion was prepared by using polyoxyethlated Cremophor RH40 as emulsifiers,propylene glycol as assistant emulsifiers and ethyl acetate as the oil *** particle size and distribution of osthole microemulsion were detected by laser particle size analyzer and transmission election *** content of osthole was determined by UV *** effects of osthole microemulsion by nasal administration on the learning and memory abilities in scopolamine-treated mice were assessed by Morris water maze and novel object recognition *** superoxide dismutase(SOD)activity,glutathione(GSH)levels and malondialdehyde(MDA)contents in the serum were examined to evaluate the oxidant *** acetyltransferase(ChAT)and acetylcholinesterase(AChE)expression in the olfactory-basal forebrain pathway were detected by immunohistochemical *** also investigated the acetylcholine(ACh)levels and the histological morphology in the ***:The average particle size of 1μg·μL-1 osthole microemulsion was less than 15 *** was characterized as spheres under the transmission electron micros

关键词： Osthole nanoemulsions Pseudo-ternary phase diagram Nasal administration cholinergic nerve circuits

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The involvement of central cholinergic system in the analgesic effect of intracerebroventricularly injected CDPcholine in acute pain models of rats

The involvement of central cholinergic system in the analges...

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第十五届国际药理学大会

作者： HAMURTEKIN EMRE GURUN MINE SIBEL Uludag Univ Medical FacultyDept.of Pharmacology16059Bursa/TURKEY Uludag Univ Medical FacultyDept.of Pharmacology16059Bursa/TURKEY

＜正＞ In the present study,intracerebroventricularly injected CDP-choline （0.5, 1, 2 micromoles） induced dose and time dependent antinociceptive effects in thermal and mechanical paw withdrawal tests and acetic acid writhing tests in rats. E-quimolar dose of CDP- choline （imicromole） and choline （imicromole） caused similar antinociceptive effects while cytidine （Imicromole） produced small,transient but statically significant antinociceptive effect. Mecamylamine, MLA and HC - 3 pretreatments completely antagonized CDP - choline induced antinocicep-tion in acute thermal and mechanical tests while HC - 3. MLA. mecamylamine and atropine pretreatments partially blocked the antinociceptive effect of CDP -choline in the acetic acid writhing test. CDPcholine did not impair motor performance of rats evaluated by rota - rod test. These results indicate that centrally administered CDP - choline induced dose and time dependent antinociception in rats by activating mainly central cholinergic nicotinic receptors through the activation of presynaptic cholinergic mechanisms.

关键词： CDP-choline antinociception acute pain cholinergic

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NP-5 Alleviating Effects of Osthol on Scopolamine-Induced cholinergic Impairments in Mice

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神经药理学报 2018年第4期8卷 104-104页

作者： LI Ming-liang LI Ying RONG Da-you TIAN Chun-yu MI Ya-xin HOU Xue-qin Institute of Pharmacology Taishan Medical UniversityTaian271016China

Objective:To investigate the effect of osthol on the central cholinergic nerve circuit in AD model mouses,,which were established by intraperitoneal injection of ***:60 health female rats were randomly divided into six *** sham operation group and model group were given intragastric administration of normal saline;the positive control group was given Aricept(3 mg·kg-1)intragastric gavage;The high,middle and low doses of the osthole groups were treated by intragastric administration of 50 mg·kg-1,25 mg·kg-1,and 12.5 mg·kg-1 osthole,respectively.30 minutes before the water maze test,except for the sham operation group who was given intraperitoneal injection of normal saline,other groups were intraperitoneally injected with scopolamine hydrobromide(3 mg·kg-1)until the experiment was *** ability of spatial learening and memory in mice was evaluted by behavioral experiments and changes and changes in the central cholinergic function of mice were examined The ability of spatial learning and memory in mice was evaluated by behavioral experiments and changes of function of the central cholinergic cricuis of mice were detected by molecular biology and ***:*** on cholinergic nerve pathways:Osthole can reduce escape latency and search distance in dementia mice,while the osthol can increase the level of ACH in the central cholinergic circuits of dementia mice.2 effects on oxidative stress pathway:The activity of SOD in the model was obvious lower than that in the normal group,while the SOD activity of each dose of osthole was higher than that in of the model *** content of MDA in the model group was obvious higher than that in the normal group,while each dose of osthole was lower than that of the model *** activity of GSH-Px in the model group was significantly lower than that in the normal group,while the activity of GSH-Px in the osthol group was higher than that in the model ***:The scopolamine-ind

关键词： Osthol Central cholinergic Alzheimer’s disease Oxidative stress

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The promise of basal forebrain cholinergic neurons in stem cell-based therapy for Alzheimer's disease

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Science Foundation in China 2016年第1期24卷 15-页

The research team led by *** NaiHe(景乃禾)at the Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,reported the successful application of stem cell-based therapy in transgenic mouse models of Alzheimer’s disease(AD).This finding was recently published in Stem Cell Reports(2015,5:776—790).

关键词： cholinergic basal transgenic promise finding exogenous endogenous devastating mature derivation

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The dual role of striatal interneurons: circuit modulation and trophic support for the basal ganglia

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Neural Regeneration Research 2024年第6期19卷 1277-1283页

作者： Elliot Wegman Marlena Wosiski-Kuhn Yu Luo Department of Molecular and Cellular Biosciences University of Cincinnati 2. Department of Emergency Medicine at the School of Medicine University of Cincinnati Neuroscience Graduate Program University of Cincinnati

Striatal interneurons play a key role in modulating striatal-dependent behaviors, including motor activity and reward and emotional processing. Interneurons not only provide modulation to the basal ganglia circuitry under homeostasis but are also involved in changes to plasticity and adaptation during disease conditions such as Parkinson’s or Huntington’s disease. This review aims to summarize recent findings regarding the role of striatal cholinergic and GABAergic interneurons in providing circuit modulation to the basal ganglia in both homeostatic and disease conditions. In addition to direct circuit modulation, striatal interneurons have also been shown to provide trophic support to maintain neuron populations in adulthood. We discuss this interesting and novel role of striatal interneurons, with a focus on the maintenance of adult dopaminergic neurons from interneuronderived sonic-hedgehog.

关键词： cholinergic dopamine GABAergic interneuron levodopa-induced dyskinesia parvalbumin sonic hedgehog striatum trophic factor

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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 *** dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and *** contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial *** 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 *** research has reported evidence that the cerebellum receives both dopaminergic and cholinergic ***,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully ***,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains ***,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 *** 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

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