1.Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal Networks.
Xiao-Wei LI ; Yi REN ; Dong-Qing SHI ; Lei QI ; Fang XU ; Yanyang XIAO ; Pak-Ming LAU ; Guo-Qiang BI
Neuroscience Bulletin 2023;39(5):731-744
Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.
Cholinergic Agents/pharmacology*
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Acetylcholine/metabolism*
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Neurons/metabolism*
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Synaptic Transmission/physiology*
2.Application of functional MRI on evaluation of cholinergic drugs and other neurotransmitter drugs and its prospect in traditional Chinese medicine evaluation.
Tianjiao FENG ; Yao ZHANG ; Zhanjun ZHANG ; Yongyan WANG
China Journal of Chinese Materia Medica 2011;36(6):810-813
This article summarizes the progress of the application of functional magnetic resonance image (fMRI) on neuropharmacology. Cholinergic drugs are types of neurotransmitters which are usually used to treat neurological disorders. fMRI is widely used in the research of evaluation of cholinergic drugs. This article systematically summerizes the research of drug evaluation on memory, attention, emotion and vision by fMRI using the cholinergic drugs for example. Combined with the charactors and disciplines of traditional Chinese medicine (TCM), this article also makes a prospect of the application of fMRI on traditional Chinese medicine evaluation, especially the drugs on brain disease and emotional modulation.
Animals
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Cholinergic Agents
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pharmacology
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Drug Evaluation
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methods
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Humans
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Magnetic Resonance Imaging
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methods
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Medicine, Chinese Traditional
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Neurotransmitter Agents
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pharmacology
3.Roles of ACh receptors in the effects of corticosterone on presympathetic neurons in the ventrolateral medulla of rats.
Wei-Zhong WANG ; Xue-Mei WANG ; Wei-Fang RONG ; Ji-Jang WANG ; Wen-Jun YUAN
Chinese Journal of Applied Physiology 2002;18(1):9-13
AIMTo investigate the roles of acetylcholine (ACh) receptors in the rapid effects of corticosterone (CORT) on the presympathetic neurons in the rostral ventrolateral medulla (RVLM) of rats, and study the non-genomic mechanism of glucocorticoid (GC) in the integration of sympathetic cardiovascular activity.
METHODSThe effects of microelectrophoresis of CORT on the discharge of the presympathetic neurons in the RVLM were observed by extracellular recording in urethane-anaesthetized rats. The responses of atropine (a blocker for M type of ACh receptor, ATR), d-tubocurarine (a blocker for N1 type of ACh receptor, d-TC) and hexamethonium (a blocker for N2 type of ACh receptor, C6) to the effects of CORT on the presympathetic neurons were investigated respectively.
RESULTSTotally 33 presympathetic neurons in the RVLM were recorded. Among them the firing rate of 25 (76%) presympathetic neurons was increased by microelectrophoresis of CORT. The effects of CORT were also positively correlated with the currents. In the other 8 presympathetic neurons, had was shown no effect after microelectrophoresis of CORT. In 10 presympathetic neurons, which discharge was increased by CORT, microelectrophoresis of ATR decreased the firing rate of these presympathetic neurons (P < 0.05), and did not fully block the excitatory effect induced by CORT. In both 7 and 6 presympathetic neurons, application of d-TC and C6 had no effect on these neurons respectively, and did not fully block the excitatory effect induced by CORT.
CONCLUSIONCORT had rapid excitatory effects on the presympathetic neurons in the RVLM, which effect might be independent on ACh receptors.
Animals ; Cholinergic Antagonists ; pharmacology ; Corticosterone ; pharmacology ; Electrophoresis, Microchip ; Male ; Medulla Oblongata ; drug effects ; physiology ; Neuromuscular Nondepolarizing Agents ; pharmacology ; Neurons ; drug effects ; physiology ; Nicotinic Antagonists ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholinergic ; physiology
4.Changes of cholinergic nerves and tumor necrosis factor-α in doxorubicin-induced rat failing heart.
Xiaoli XU ; Jurong ZENG ; Xiaojiang YU ; Man MI ; Jin HOU ; Lei SUN ; Dongling LI ; Weijin ZANG
Journal of Southern Medical University 2012;32(8):1139-1142
OBJECTIVETo investigate the changes of cholinergic nerves in doxorubicin (DOX)-induced rat failing heart and tumor necrosis factor-α (TNF-α) in the heart tissue and serum.
METHODSAdult Sprague-Dawley rats were randomized into control (n=10) and DOX-induced chronic heart failure (CHF) groups (n=15), and in the latter group, the rats were given intraperitoneal injections of 2.5 mg/kg DOX once a week for 6 weeks, with a total cumulative dose of 15 mg/kg. The control rats were injected with normal saline (1 ml/week). Karnovsky-Roots histochemical staining combined with point counting was used to demonstrate the distribution of cholinergic nerves in the heart. The expression levels of TNF-α in the heart tissue and serum were determined with ELISA.
RESULTSPositively stained cholinergic nerves were found in all the rat hearts in the two groups, but in CHF group, the point counts of cholinergic nerves were significantly lower than that of the control group (P<0.01). Compared with the control rats, those with DOX-induced CHF showed elevated levels of TNF-α both in the heart tissue and in the serum (P<0.01).
CONCLUSIONIn rats with DOX-induced CHF, the parasympathetic nervous system is down-regulated in the failing heart, and the diminished cholinergic anti-inflammatory pathway may play an important role in the progression of CHF.
Animals ; Cholinergic Agents ; pharmacology ; Cholinergic Fibers ; drug effects ; Doxorubicin ; pharmacology ; Heart ; drug effects ; innervation ; Heart Failure ; chemically induced ; metabolism ; Male ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism
5.The Effect of Urocortin 1 on Motility in Isolated, Vascularly Perfused Rat Colon.
Il Young YOU ; Seungho LEE ; Ki Bae KIM ; Hee Seung LEE ; Jong Soon JANG ; Myeongho YEON ; Joung Ho HAN ; Soon Man YOON ; Hee Bok CHAE ; Seon Mee PARK ; Sei Jin YOUN
The Korean Journal of Gastroenterology 2015;65(5):283-290
BACKGROUND/AIMS: Urocortin 1, a corticotropin-releasing factor related peptide, increases colonic motility under stressful conditions. We investigated the effect of urocortin 1 on colonic motility using an experimental model with isolated rat colon in which the blood flow and intestinal nerves were preserved. Furthermore, we assessed whether this effect was mediated by adrenergic or cholinergic nerves. METHODS: Colonic motility was measured in the proximal and distal parts of resected rat colon. The colon resected from the peritoneum was stabilized, and then urocortin 1 (13.8, 138, 277, and 1,388 pM) was administered via a blood vessel. Motility index was measured in the last 5 min of the 15 min administration of urocortin 1 and expressed as percentage change from baseline. Subsequently, the change in motility was measured by perfusing urocortin 1 in colons pretreated with phentolamine, propranolol, hexamethonium, atropine, or tetrodotoxin. RESULTS: At concentrations of 13.8, 138, 277, and 1,388 pM, urocortin 1 increased the motility of proximal colon (20.4+/-7.2%, 48.4+/-20.9%, 67.0+/-25.8%, and 64.2+/-20.9%, respectively) and the motility of distal colon (3.3+/-3.3%, 7.8+/-7.8%, 71.1+/-28.6%, and 87.4+/-32.5%, respectively). The motility induced by urocortin 1 was significantly decreased by atropine to 2.4+/-2.4% in proximal colon and 3.4+/-3.4% in distal colon (p<0.05). However, tetrodotoxin, propranolol, phentolamine, and hexamethonium did not inhibit motility. CONCLUSIONS: Urocortin 1 increased colonic motility and it is considered that this effect was directly mediated by local muscarinic cholinergic receptors.
Animals
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Colon/*drug effects/physiology
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Injections, Intravenous
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Male
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Muscle Contraction/drug effects
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Neurotransmitter Agents/pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Cholinergic/chemistry/metabolism
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Urocortins/isolation & purification/*pharmacology
6.Mechanism of UV light-induced photorelaxation in isolated rat aorta.
Joo Heon KIM ; Yonggeun HONG ; Cheol Soo SHIM
Journal of Veterinary Science 2000;1(2):81-86
Isolated rat thoracic aorta which is pharmacologically precontracted by phenylephrine induces photorelaxation when exposed to long wave length UV-light. The aim of the present study was to characterize the mechanism of UV-light induced by photorelaxation in the rat aorta. 1. UV light relaxed both endothelium-intact and -denuded rat aortic rings contracted by phenylephrine. The magnitude of relaxation on UV light was dependent on the exposure time and slightly greatly in endothelium-denuded rings than in endothelium-intact preparations. 2. L-NAME (10 nM-100 uM) but not D-NAME completely inhibited the photorelaxation in a concentration dependent manner. 3. The UV-induced relaxation was inhibited by methylene blue (1 -100 uM), and verapamil (100 nM), and removal of extracellular Ca2+. In contrast, UV-light induced photorelaxation was potentiated by N(w)-nitro-Larginine (L-NOARG) treatment. 4. In immunocytochemical analysis of UV-light induced iNOS and eNOS expression in rat aortas, at which expression levels were increased in a time-dependent manner on UV-irradiation in aortic endothelium and smooth muscle, respectively. These results suggest that UV light-induced photorelaxation may be due to nitric oxide from exogenously administered L-arginine as well as endogenous nitric oxide donors such as amino acid and arginine derivatives. Additional suggestion is that UV light stimulates the expression of nitric oxide synthases, and its activity for nitric oxide generation is dependent on cytosolic Ca2+ originated from extracellular space.
Acetylcholine/pharmacology
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Animals
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Aorta, Thoracic/drug effects/*physiology/radiation effects
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Calcium Channel Blockers/pharmacology
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Cholinergic Agents/pharmacology
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Endothelium, Vascular/drug effects/physiology/radiation effects
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Enzyme Inhibitors/pharmacology
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Female
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Male
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Methylene Blue/pharmacology
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NG-Nitroarginine Methyl Ester/pharmacology
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Nitric Oxide Synthase/antagonists & inhibitors/metabolism
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Phenylephrine/pharmacology
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Rats
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Rats, Sprague-Dawley
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*Ultraviolet Rays
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Vasoconstrictor Agents/pharmacology
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Vasodilation/drug effects/*radiation effects
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Vasodilator Agents/pharmacology
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Verapamil/pharmacology
7.Pharmacological Modulation of Vagal Nerve Activity in Cardiovascular Diseases.
Longzhu LIU ; Ming ZHAO ; Xiaojiang YU ; Weijin ZANG
Neuroscience Bulletin 2019;35(1):156-166
Cardiovascular diseases are life-threatening illnesses with high morbidity and mortality. Suppressed vagal (parasympathetic) activity and increased sympathetic activity are involved in these diseases. Currently, pharmacological interventions primarily aim to inhibit over-excitation of sympathetic nerves, while vagal modulation has been largely neglected. Many studies have demonstrated that increased vagal activity reduces cardiovascular risk factors in both animal models and human patients. Therefore, the improvement of vagal activity may be an alternate approach for the treatment of cardiovascular diseases. However, drugs used for vagus nerve activation in cardiovascular diseases are limited in the clinic. In this review, we provide an overview of the potential drug targets for modulating vagal nerve activation, including muscarinic, and β-adrenergic receptors. In addition, vagomimetic drugs (such as choline, acetylcholine, and pyridostigmine) and the mechanism underlying their cardiovascular protective effects are also discussed.
Acetylcholine
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pharmacology
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Animals
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Cardiovascular Diseases
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drug therapy
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Cholinergic Agents
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therapeutic use
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Humans
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Receptors, Muscarinic
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drug effects
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Sympathetic Nervous System
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drug effects
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physiopathology
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Vagus Nerve
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drug effects
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physiopathology
8.Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor.
Huiyoung KWON ; Ji Wook JUNG ; Young Choon LEE ; Jong Hoon RYU ; Dong Hyun KIM
Chinese Journal of Natural Medicines (English Ed.) 2018;16(6):428-435
Artemisia capillaris Thunberg is a medicinal plant used as a traditional medicine in many cultures. It is an effective remedy for liver problems including hepatitis. Recent pharmacological reports have indicated that Artemisia species can exert various neurological effects. Previously, we reported a memory-enhancing effect of Artemisia species. However, the mechanisms underlying the neuroprotective effect of A. capillaris (AC) are still unknown. In the present study, we investigated the effect of an ethanol extract of AC on ischemic brain injury in a mouse model of transient forebrain ischemia. The mice were treated with AC for seven days, beginning one day before induction of transient forebrain ischemia. Behavioral deficits were investigated using the Y-maze. Nissl and Fluoro-jade B staining were used to indicate the site of injury. To determine the underlying mechanisms for the drug, we measured acetylcholinesterase activity. AC (200 mg·kg) treatment reduced transient forebrain ischemia-induced neuronal cell death in the hippocampal CA1 region. The AC-treated group also showed significant amelioration in the spontaneous alternation of the Y-maze test performance, compared to that in the untreated transient forebrain ischemia group. Moreover, AC treatment showed a concentration-dependent inhibitory effect on acetylcholinesterase activity in vitro. Finally, the effect of AC on forebrain ischemia was blocked by mecamylamine, a nonselective nicotinic acetylcholine receptor antagonist. Our results suggested that in a model of forebrain ischemia, AC protected against neuronal death through the activation of nicotinic acetylcholine receptors.
Acetylcholinesterase
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metabolism
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Animals
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Artemisia
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Cell Death
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drug effects
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Cholinergic Antagonists
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pharmacology
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Disease Models, Animal
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Ethanol
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chemistry
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Hippocampus
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pathology
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physiopathology
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Ischemic Attack, Transient
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drug therapy
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pathology
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physiopathology
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Male
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Mecamylamine
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pharmacology
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Memory
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drug effects
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Mice
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Mice, Inbred C57BL
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Models, Neurological
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Neuroprotective Agents
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administration & dosage
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pharmacology
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Phytotherapy
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Plant Components, Aerial
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chemistry
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Plant Extracts
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administration & dosage
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pharmacology
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Receptors, Cholinergic
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metabolism
9.The role of AT1 receptor in the changes in TH immunoreactivity of LC induced by brain cholinergic stimulation.
Qi-Ying YAO ; Lei SUN ; Chun-Yan WANG ; Chun-Ling JIANG
Chinese Journal of Applied Physiology 2006;22(1):45-48
AIM AND METHODSIn the present study, we investigated the TH immunoreactivity and the expression of angiotensin AT1 receptor in locus coeruleus after intracerebroventricular (i. c. v.) injection of carbachol in conscious SD rats with immunohistochemistry. Meanwhile the effects of blocking AT1 receptor were also observed.
RESULTSBoth mean optical density and number of TH and AT1 immunoreactive positive neurons were markedly increased in locus coeruleus after 40 minutes of i.c.v. injection of carbachol (0.5 microg). The enhancement was significantly reduced by i. c. v. injection of losartan.
CONCLUSIONThe results above suggest that i. c. v. injection of cholinergic agonist carbachol can enhance the activity of adrenergic neurons and the expression of AT1 receptor in locus coeruleus. The blockade of AT1 receptor may down regulate the above action induced by carbachol in locus coeruleus.
Animals ; Brain ; Carbachol ; pharmacology ; Cholinergic Agents ; pharmacology ; Injections, Intraventricular ; Locus Coeruleus ; drug effects ; metabolism ; Losartan ; pharmacology ; Male ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; metabolism ; Tyrosine 3-Monooxygenase
10.Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.
Da Un JEONG ; Jin Hwan OH ; Ji Eun LEE ; Jihyeon LEE ; Zang Hee CHO ; Jin Woo CHANG ; Won Seok CHANG
Yonsei Medical Journal 2016;57(1):165-172
PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.
Acetylcholine/metabolism
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Alzheimer Disease
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Animals
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Antibodies, Monoclonal/*pharmacology
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Basal Forebrain/*drug effects/metabolism
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Cholinergic Agents/administration & dosage/*pharmacology
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Cholinergic Neurons/*drug effects/metabolism
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Fluorodeoxyglucose F18
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GABAergic Neurons/*drug effects/metabolism
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Glucose/*metabolism
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Gyrus Cinguli/*drug effects/metabolism
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Humans
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Injections
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Maze Learning
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Motor Activity/physiology
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Positron-Emission Tomography
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Rats
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Ribosome Inactivating Proteins, Type 1/*pharmacology