• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.28-34
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• 1993

Using in vitro autoradiography with a digital autoradiography system and radioreceptor assay, the distribution and the binding characteristics of the muscarinic cholinergic receptors (mAChR) were studied in regions of rat brain. Radioreceptor assay revealed that mAChR could be measured with saturation binding assay in the brain and heart homogenates: No difference in Kd or Bmax of the brain or heart was found between the normal Wistar rats and SHR rats. Specific binding of $^3H$ quinuclidinyl benzilate (QNB) increased and saturation was reached by 2 hours after incubation with slide-mounted brain tissue. The distribution of mAChR was heterogeneous along the fields of brain. Affinity (Kd) of mAChR was not different significantly among cortex, hippocampus and caudate-putamen. No difference was found between normal rats and SHR strain. More receptors (Bmax) were found in the cortex and hippocampus than in the caudate-putamen in normal rats. More receptors were found in the cortex and caudate-putamen in SHR rats than in normal rats. Radioreceptor assay and digital autoradiographic analysis of affinity and number of mAChR gave the same results. With the above findings, we concluded that we could use digital autoradiographic system with $^3H$-QNB in the characterization of mAChR of rats and that the cortex and caudate-putamen of SHR strain rats have more receptors than those of normal rats.

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.472-477
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• 1999

To elucidate the action of the cholinergic and adrenergic nerve on isolated gastric fundus smooth muscle of rabbit, the effects of electrical transmural stimulation were investigated in the presence of atropine, cholinergic receptor blocker; phentolamine, nonselective ${\alpha}$-adrenergic receptor blocker; propranolol, nonselective ${\beta}$-adrenergic receptor blocker and L-arginine from the isometric contraction of physiological recording system. 1. The contractile response induced by electrical transmural stimulation was increased as the frequency(1~32Hz)-dependent manner on the isolated gastric fundus smooth muscle. 2. The contractile response induced by electrical transmural stimulation was markedly inhibited by the pretreatment of atropine($1{\mu}M$). 3. The contractile response induecd by electrical transmutal stimulation was inhibited by the pretreatment of phentolamine($1{\mu}M$). 4. The relaxative response induced by electrical transmural stimulation on presence of atropine ($1{\mu}M$) was inhibited by the pretreatment of propranolol($1{\mu}M$). 5. The relaxative responses on precontraction induced by histamine($10{\mu}M$) with guanethidine ($50{\mu}M$) and atropine($1{\mu}M$) by electrical transmural stimulation were increased by L-arginine (1mM). These findings suggest that it was the excitatory action of cholinergic and ${\alpha}$-adrenergic nerve, and the inhibitory action of ${\beta}$-adrenergic nerve and nonadrenergic noncholinergic nerve on the isolated gastric fundus smooth muscle of rabbit.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.67-76
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• 2008

Objectives : Amnesia is theloss or impairment of memory, caused by physical injury, disease, drugs, or emotional trauma. Recently, the average life span is increasing, while at the same time, the incidence of dementia-like diseases in conjunction with amnesia are also increasing. Therefore learning and memory are very important issues in modern society. Ancient Korean physicians used several herbs to treat dementia and these herbal effects were described in Korean herbal books. Among them are some reports on several cognitive-enhancing herbs which have since been shown to improve dementia in recent pharmacological studies, such as Panax ginseng; however, the facilitatory effects of many Korean cognitive-enhancing herbs on learning and memory are limited. Learning and memory are essential requirements for every living organism in order to cope with environmental demands; cholinergic systems are known to be involved in learning and memory. Methods : In this study, the effects of Acori graminei rhizoma (AGR, 石菖蒲) on learning and memory were investigated by Morris water maze, eight-arm radial maze, and the effects on the central cholinergic system of rats injected with scopolamine. Results : In the water maze, the experimental animals were trained to find a platform in a fixed position for 6 days and then received a 60 sec probe trial in which the platform was removed from the pool on the 7th day. In the eight-arm radial maze, the animals were tested four times per day for 6 days. Scopolamine impaired performance of the maze tests and reduced activity of acetylcholinesterase (AchE) in the hippocampus, which is a marker for the central cholinergic system. There were significant reversals from the scopolamine-induced deficits on learning and memory in these tests, through daily administrations of AGR (100 mg/kg, p.o.) over 14 consecutive days. These treatments also reduced the loss of cholinergic activity in the hippocampus induced by scopolamine. Conclusions : These results demonstrated that AGR ameliorated learning and memory deficits by affecting the central acetylcholine system.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.257-267
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• 2018

The present study aimed to evaluate the cinnamic acid effect on memory impairment, oxidative stress, and cholinergic dysfunction in streptozotocin (STZ)-induced diabetic model in mice. In this experimental study, 48 male Naval Medical Research Institute (NMRI) mice (30-35 g) were chosen and were randomly divided into six groups: control, cinnamic acid (20 mg/kg day, i.p.), diabetic, and cinnamic acid-treated diabetic (10, 20 and 40 mg/kg day, i.p.). Memory was impaired by administering an intraperitoneal STZ injection of 50 mg/kg. Cinnamic acid was injected for 40 days starting from the 21st day after confirming STZ-induced dementia to observe its therapeutic effect. Memory function was assessed using cross-arm maze, morris water maze and passive avoidance test. After the administration, biochemical parameters of oxidative stress and cholinergic function were estimated in the brain. Present data indicated that inducing STZ caused significant memory impairment, whereas administration of cinnamic acid caused significant and dose-dependent memory improvement. Assessment of brain homogenates indicated cholinergic dysfunction, increase in lipid peroxidation and reactive oxygen species (ROS) levels, and decrease in glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities in the diabetic group compared to the control animals, whereas cinnamic acid administration ameliorated these indices in the diabetic mice. The present study demonstrated that cinnamic acid improves memory by reducing the oxidative stress and cholinergic dysfunction in the brain of diabetic mice.

• Journal of Nutrition and Health
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• v.32 no.8
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• pp.864-869
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• 1999

To investigate the effect of dietary phosphatidylcholine(PPC) supplement on memory improvement, biochemical study on the brain, and morphometric studies on the cholinergic neurons in the rat basal forebrain were undertaken. The pregnancy rats were divided into the normal control, the choline deficient and the PPC supplemental groups according to quantity of the PPC in diet. According to choline deficiency and PPC supplement after birth, the neonate rate of the normal control group were subdivided into the control diet(N-N) and the PPC supplied (N-S) groups, the choline deficient group were subdivided into the continually deficient (D-D), the control diet(D-N) and the PPC supplied groups(D-S), and the PPC supplemental group were subdivided into the control diet (S-N)and the continually supplied (S-S)group. The PPC supplemented diet was added 2% egg PPC in AIN 76 formula diet. PPC concentrations and cholinesterase(CE) activities were measured in the serum, the liver and the brain, respectively. Immunohistochemical stains for choline acetyltransferase(ChAT) was employed for the morphological and morphometric studies. The maze test was undertaken to evaluate memory improvement. PPC concentration and CE activities in the serum, liver and the brain were high in the PPC supplemental groups and low in the choline deficient groups. ChAT immunoreactivity neurons at the medial septal diagonal bond complex and the basal forebrain nucleus of Meynert were reduced in the choline deficient groups. Average failure rate for the maze test was the lowest in the S-S group and the highest in the D-D group. Insufficient choline suppley during the neuronal development would result in cholinergic neuronal damage, which could be prevented by adequate PPC supplement. It is consequently suggested that PPC supplement may be effective on memory improvement by maintaining the cholinergic neuronal activity in the basal forebrain of the rats.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.747-755
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• 2003

The aim of the present study was to clarify whether cotinine affects the release of catecholamines (CA) from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, in comparison with the response of nicotine. Cotinine (0.3∼3 mM), when perfused into an adrenal vein for 60 min, inhibited CA secretory responses evoked by ACh (5.32 mM), DMPP (a selective neuronal nicotinic agonist, 100 $\mu$M for 2 min) and McN-A-343 (a selective muscarinic $M_1 -agonist, 100 \mu$ M for 2 min) in dose- and time-dependent manners. However, cotinine did not affect CA secretion by high $K^+$ (56 mM). Cotinine itself also failed to affect basal CA output. Furthermore, in the presence of cotinine (1 mM), CA secretory responses evoked by Bay-K-8644 (an activator of L-type $Ca^{2+}$ channels, 10 $\mu$ M) and cyclopiazonic acid (an inhibitor of cytoplasmic $Ca^{2+}-ATPase, 10 \mu$ M) were relative time-dependently attenuated. However, nicotine (30$\mu$ M), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh and high $K^+$, followed by the inhibition later, while it time-dependently depressed the CA release evoked by McN-A-343 and DMPP. Taken together, these results suggest that cotinine inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by the direct membrane-depolarization. It seems that this inhibitory effect of cotinine may be exerted by the cholinergic blockade, which is associated with blocking both the calcium influx into the rat adrenal medullary chromaffin cells and $Ca^{2+}$ release from the cytoplasmic calcium store. It also seems that there is a big difference in the mode of action between cotinine and nicotine in the rat adrenomedullary CA secretion.

• Archives of Pharmacal Research
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• v.18 no.2
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• pp.121-128
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• 1995

The role of nitric oxide (NO) in non-adrenegic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the dorsal part of the fuinea-pig gastric fundus. In the presence of atropine and guanethidine, a low frequency-dependent relaxsations which were not affected by adrenergic and cholinergic blockage but abolished by tetrodotoxin. $N^G$-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stiumulations but not the relaxations to exogenous nitric oxide. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer, D-arginine. Exgenous administration of No caused concentration -dependent relaxations which showed a similarity to those obtained with electrical simultaion. Hemoglobin, a NOscavenger, abolished the NO-induced relaxations and also markedly reduced those induced by electrical simultaion. The inhibitory effect os hemoglobin was similar to that of L-NNA. Application of ATP caused weak relaxations compared with those to electrical stimultaion, which were unaffected by L-NNA. Exogenously applied vasoactive intestinal polypeptide (VIP) induced concentration-dependent relaxation which was not affected by L-NNA. These results suggest that NO is produced and released mainly as a neurotransmitter from enteric neurons during NANC relaxation induced by low frequencies and short trains of electrical simulation and has a main role in NANC neurotransmission at relaxation induced by these electrical simultaions in the guinea-pig gastric fundus.

• Archives of Craniofacial Surgery
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• v.22 no.1
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• pp.1-10
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• 2021

Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002, and has also been used widely for aesthetic purposes such as hyperhidrosis, body shape contouring, and other noninvasive facial procedures. BoNT-A inhibits presynaptic exocytosis of acetylcholine (ACh)-containing vesicles into the neuromuscular junction at cholinergic nerve endings of the peripheral nervous system, thereby paralyzing skeletal muscles. ACh is the most broadly used neurotransmitter in the somatic nervous system, preganglionic and postganglionic fibers of parasympathetic nerves, and preganglionic fibers or postganglionic sudomotor nerves of sympathetic nerves. The scientific basis for using BoNT-A in various cosmetic procedures is that its function goes beyond the dual role of muscle paralysis and neuromodulation by inhibiting the secretion of ACh. Although the major target organs for aesthetic procedures are facial expression muscles, skeletal body muscles, salivary glands, and sweat glands, which are innervated by the somatic or autonomic nerves of the peripheral cholinergic nerve system, few studies have attempted to directly explain the anatomy of the areas targeted for injection by addressing the neural physiology and rationale for specific aesthetic applications of BoNT-A therapy. In this article, we classify the various cosmetic uses of BoNT-A according to the relevant component of the peripheral nervous system, and describe scientific theories regarding the anatomy and physiology of the cholinergic nervous system. We also review critical physiological factors and conditions influencing the efficacy of BoNT-A for the rational aesthetic use of BoNT-A. We hope that this comprehensive review helps promote management policies to support long-term, safe, successful practice. Furthermore, based on this, we look forward to developing and expanding new advanced indications for the aesthetic use of BoNT-A in the future.

• Development and Reproduction
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• v.11 no.3
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• pp.235-243
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• 2007

Human umbilical cord blood(HUCB) contains a rich source of hematopoietic stem cells, mesenchymal stem cells and endothelial cell precursors. Mesenchymal stem cells(MSCs) in HUCB are multipotent stem cells, differ from hematopoietic stem cells and can be differentiated into neural cells. We studied on transdifferentiation-promoting conditions in neural cells and cholinergic neuron induction of HUCB-derived MSCs. Neural differentiation was induced by addingdimethyl sulphoxide(DMSO) and butylated hydroxyanisole(BHA) in Dulbeco's Modified Essential Medium(DMEM) and fetal bovine serum(FBS). Differentiation of MSCs to cholinergic neurons was induced by combined treatment with basic fibroblast growth factor(bFGF), retinoic acid(RA) and sonic hedgehog(Shh). MSCs treated with DMSO and BHA rapidly assumed the morphology of multipolar neurons. Both immunocytochemistry and RT-PCR analysis indicated that the expression of a number of neural markers including $\beta$-tubulin III, GFAP and MBP, was markedly elevated during this acute differentiation. The differentiation rate was about $32.3{\pm}2.9%$ for $\beta$-tubulin III-positive cells, $11.0{\pm}0.9%$ for GFAP, and $9.4{\pm}1.0%$ for Gal-C. HUCB-MSCs treated combinatorially with bFGF, RA and Shh were differentiated into cholinergic neurons. After cholinergic neuronal differentiation, the $\beta$-tubulin III-positive cell population of total cells was $31.3{\pm}3.2%$ and of differentiated neuronal population, $70.0{\pm}7.8%$ was ChAT-positive showing 3 folds higher in cholinergic population than neural induction. Conclusively, HUCB-derived MSCs can be differentiated into neural and cholinergic neurons and these findings suggest that HUCB are alternative cell source of treatment for neurodegenerative diseases such as Alzheimer's disease.

• Applied Microscopy
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• v.26 no.2
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• pp.137-155
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• 1996

The development of the ganglia of the trachea was studied by electron microscopy in human fetuses ranging from 40 mm to 260 mm crown rump length. At 40 mm fetus, the tracheal ganglia was observed in the submucosa of the trachea. The primitive ganglia consisted of neuroblasts, undifferentiated cells, and unmyelinated nerve fibers. At 50 mm fetus, the neuroblast and their processes in the tracheal ganglia ware ensheathed by the bodies or processes of satellite cells. The cytoplasm of the neuroblast contained rough endoplasmic reticulum, mitochondria, Golgi complex, and ribosomes. At 70 mm fetus, cholinergic and adrenergic axon terminals were observed. Cholinergic axon terminals with agranular vesicles were abundant in the tracheal ganglia with increasing age. During next prenatal stage from 100 mm fetus, the ganglion cells and its processes were completely covered by a thin processes of the satellite cells. Unmyelinated nerve fibers were also completely ensheathed by processes of Schwann cell. Synaptic contacts between the cholinergic axon and dendrite of ganglion cells and a few dendrodendritic synapses were first observed at 100 mm fetus. The granule-containing cells were first identified in the tracheal ganglia at 200 mm fetus. These findings indicate that tracheal ganglia of human fetus resembles other parasympathetic and sympathetic ganglia, but not the enteric ganglia.