• The Korean Journal of Physiology and Pharmacology
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• v.24 no.6
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• pp.517-527
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• 2020

Layer 2/3 pyramidal neurons (L2/3 PyNs) of the cortex extend their basal dendrites near the soma and as apical dendritic tufts in layer 1, which mainly receive feedforward and feedback inputs, respectively. It is suggested that neuromodulators such as serotonin and acetylcholine may regulate the information flow between brain structures depending on the brain state. However, little is known about the dendritic compartment-specific induction of synaptic transmission in single PyNs. Here, we studied layer-specific serotonergic and cholinergic induction of long-term synaptic plasticity in L2/3 PyNs of the agranular insular cortex, a lateral component of the orbitofrontal cortex. Using FM1-43 dye unloading, we verified that local electrical stimulation to layers 1 (L1) and 3 (L3) activated axon terminals mostly located in L1 and perisomatic area (L2/3). Independent and AMPA receptor-mediated excitatory postsynaptic potential was evoked by local electrical stimulation of either L1 or L3. Application of serotonin (5-HT, 10 μM) induced activity-dependent longterm depression (LTD) in L2/3 but not in L1 inputs. LTD induced by 5-HT was blocked by the 5-HT₂ receptor antagonist ketanserin, an NMDA receptor antagonist and by intracellular Ca²⁺ chelation. The 5-HT₂ receptor agonist α-me-5-HT mimicked the LTD induced by 5-HT. However, the application of carbachol induced muscarinic receptor-dependent LTD in both inputs. The differential layer-specific induction of LTD by neuromodulators might play an important role in information processing mechanism of the prefrontal cortex.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.337-345
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• 2014

The present study examined the effects of soybean-derived phosphatidylserine (SB-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The cognitive improving efficacy of SB-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing cholineacetyl transferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. A positron emission tomography (PET) scanning the rat brain was by performed administer 18F-Fluorodeoxy-glucose (18F-FDG). The rats with TMT injection showed impaired learning and memory of the tasks and treatment with SB-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd day compared to that of the MCT group. In the retention test, the SB-PS group showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, SB-PS 50 group significantly alleviated the loss of acetyl cholinergic neurons in the hippocampus compared to that of the MCT group. Treatment with SB-PS significantly increased the CREB positive neurons in the hippocampus as compared to that of the MCT group. In addition, SB-PS groups increased the glucose uptake in the hippocampus and SB-PS 50 group increased the glucose uptake in the frontal lobe, as compared to that of the MCT group. These results suggest that SB-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.317-328
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• 2018

Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPL-treated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.189-195
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• 1988

This study aimed to investigate the autonomic innervations of human vas deferens and the effect of diazepam, a benzodiazepine sedative antianxiety drug, on the smooth muscle contractility of vas deferens. The specimens were obtained from healthy volunteers undergoing elective vasectomy with local anesthesia. The muscle preparation did not show any spontaneous contraction, but showed a good contraction induced by norepinephrine exerting the strongest response at $33^{\circ}C$. Phentolamine inhibited the norepinephrine-induced contraction concentration-dependently. Isoproterenol, a beta-adrenergic agonist evoked a considerable extent of contraction, and this contractile activity was antagonized by propranolol, a beta-adrenergic blocking agent. Acetylcholine induced a dashing contraction of the human vas deferens, and atropine, a muscarinic receptor blocking agent abolished the acetylcholine-induced contraction. Diazepam inhibited the norepinephrine-induced contraction in a concentration dependent manner. These results suggest that the smooth muscle of human vas deferens has cholinergic muscarinic and beta adrenergic receptors as well as the predominant alpha adrepergic receptor. Diazepam inhibits the motility, especially norepinephrine-induced contraction of human vas deferens.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.299-306
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• 2013

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

• The Journal of Korean Medicine
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• v.25 no.4
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• pp.1-7
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• 2004

Objective : This study was designed to examine the effects of orally administered Prunus persica water extract (PPE), which is used as herbal medicine, for treatment of Yu Xue (stasis of blood) and tacrine on the basal concentration of extracellular acetylcholine in the hippocampus of rats. Methods: To investigate the effects of PPE and tacrine on concentration of extracellular acetylcholine in the hippocampus of rats, the microdialysis technique, under the same experimental conditions, was used. And we used male Wistar rats which were 7 weeks of age and 210-290 g. PPE was extracted with boiling water, and the rats were anesthetized with pentobarbital Na. Their skulls were exposed and a hole was drilled for implantation of a microdialysis probe. In order to increase the recovery of acetylcholine, a probe with a long membrane was used. One day after surgery, the microdialysis probe was perfused with Ringer's solution at a flow rate of 1.5 l/min. The acetylcholine concentration in dialysis samples was measured by high-performance liquid chromatography (HPLC) with electrochemical detection. AChE activity was measured using the radiometric method, as described by Sherman. Results : The comparative effects of PPE and tacrine on hippocampal extracellular acetylcholine concentration was that these cholinesterase inhibitors produced dose-dependent increases in the extracellular acetylcholine concentration. And the effect of PPE and tacrine on rat brain AChE activity was that PPE produced maximal inhibition at 1 h after administration, when AChE activity was 44% of the intact level. AChE activity gradually recovered thereafter, and reached 78% of the intact level at 12 h after administration. Conclusion : In this study, PPE has a potent activity and a long-lasting effect on the central cholinergic system, in terms of the basal concentration of extracellular acetylcholine in the hippocampus and the AChE activity in the brain of rats. And oral administration of PPE increased dose-dependently the basal concentration of extracellular acetylcholine in the hippocampus of rats. PPE may be one of the more useful cholinesterase inhibitors for the treatment of Alzheimer's disease.

• Sleep Medicine and Psychophysiology
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• v.9 no.1
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• pp.9-13
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• 2002

Alzheimer's disease (AD) is one of the most common and devastating dementing disorders of old age. Most AD patients showed significant alternation of sleep structure as well as cognitive deficit. Typical findings of sleep architecture in AD patients include lower sleep efficiency, higher stage 1 percentage, and greater frequency of arousals. The slowing of EEG activity is also noted. Abnormalities in REM sleep are of particular interest in AD because the cholinergic system is related to both REM sleep and AD. Several parameters representing REM sleep structure such as REM latency, the amount of REM sleep, and REM density are change in patients with AD. Especially, measurements of EEG slowing during tonic REM sleep can be used as an EEG marker for early detection of possible AD. In addition, a structural defect in the suprachiasmatic nucleus is suggested to cause various chronobiological alternations in AD. Most of alternations related to sleep make sleep disturbances common and disruptive symptoms of AD. In this article, the author reviewed the alternation of sleep structure and circadian rhythm in AD patients.

• The Korean Journal of Physiology
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• v.16 no.2
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• pp.147-152
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• 1982

The present study was undertaken to investigate effects of Perillae Folium juice on the respiration and blood pressure in cats. Also studied was the mechanism of depressor action of PFJ. The results obtained are as follows; 1) Following administration of 0.2 ml/kg, 0.4 ml/kg and 0.6 ml/kg PFJ into cats the maximum depressor responses observed were 48.5+3.6 mmHg, 56.8+4.3 mmHg and 71.1+2.9 mmHg respectively. 2) Depressor responses to PFJ were blocked makedly by atropine and partially by propranolol. Therefore it is strongly suggested that depressor action of PFJ results mainly from cholinergic effect and partly from activity of ${\beta}-receptor$. 3) After administration of PFJ into cats tachypnea preceded by a short period of apnea was observed invariably.

• Journal of Chest Surgery
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• v.34 no.8
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• pp.634-639
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• 2001

Central anticholinergic syndrome is defined as an absolute or relative reduction in cholinergic activity in the central nervous system and has a wide variety of manfestations. It is associated with almost any drug given during anesthesia, except neuromuscular relaxants, and treated with the cholinesterase inhibitor physostigmine. The diagnosis of central anticholinergic syndrome is often made when symptoms resolve promptly after the administration of physostigmine. We present a case of a central anticholinergic syndrome diagnosed by treatment with physostigmine, in a patient who received closure of patent foramen ovale associated with stroke.

• Journal of the Korean Chemical Society
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• v.60 no.2
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• pp.125-130
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• 2016

With the goal of developing Alzheimer’s disease therapeutics, we have designed and synthesized new triazole linked decursinol derivatives having potency inhibitory activities against cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)]. Since inhibition of cholinesterase (ChE) is still considered to be one of the most effective targets to treat AD patients, many new classes of ChE inhibitors have been synthesized. In an effort of identifying new type of cholinergic drug, decursinol derivatives 11-17 have been synthesized between decursinol and other biological interesting compounds such as lipoic acid, polyphenols, etc by using the click reaction and then evaluated their biological activities. Compound 12 (IC₅₀ = 5.89 ± 0.31 mM against BuChE) showed more effective inhibitory activity against BuChE than galantamine (IC₅₀ = 9.4 ± 2.5 mM). Decursinol derivatives can be considered a new class inhibitor for BuChE and can be applied to be a novel drug candidate to treat AD patients.