The present study was undertaken to explore the potential of erythropoietin in memory deficits of mice. Memory impairment was produced by scopolamine (0.5 mg/kg, $i.p.$) and intracerebroventricular streptozotocin (i.c.v STZ, 3 mg/kg, $10{\mu}l$, $1^{st}$ and $3^{rd}$ day) in separate groups of animals. Morris water-maze test was employed to assess learning and memory. The levels of brain thio-barbituric acid reactive species (TBARS) and reduced glutathione (GSH) were estimated to assess degree of oxidative stress. Brain acetylcholinesterase enzyme (AChE) activity was also measured. Scopolamine/streptozotocin administration induced significant impairment of learning and memory in mice as indicated by marked decrease in Morris water-maze performance. Scopolamine/streptozotocin administration also produced a significant enhancement of brain AChE activity and brain oxidative stress (an increase in TBARS and a decrease in GSH) levels. Treatment of erythropoietin (500 and 1,000 IU/Kg i.p.) significantly reversed scopolamine- as well as streptozotocin-induced learning and memory deficits along with attenuation of those-induced rise in brain AChE activity and brain oxidative stress levels. It may be concluded that erythropoietin exerts a beneficial effect in memory deficits of mice possibly through its multiple actions including potential anti-oxidative effect.
Several lines of evidence indicate that adenosine $A_{2A}$ agonist disrupts spatial working memory. However, it is unclear which stages of learning and memory are affected by the stimulation of adenosine $A_{2A}$ receptor. To clarify these points, we employed CV-1808 as adenosine $A_{2A}$ agonist and investigated its effects on acquisition, consolidation, and retrieval phases of learning and memory using passive avoidance and the Morris water maze tasks. During the acquisition phase, CV-1808 (2-phenylaminoadenosine, 1 and 2 mg/kg, i.p.) decreased the latency time in passive avoidance task and the mean savings in the Morris water maze task, respectively. During the consolidation and retrieval phase tests, CV-1808 did not exhibited any effects on latency time in passive avoidance task and the mean savings in the Morris water maze task. These results suggest that CV-1808 as an adenosine $A_{2A}$ agonist impairs memory acquisition but not consolidation or retrieval.
Three types of learning and memory tests (Morris water maze, active and passive avoidance) were performed in rats following intracerebroventricular infusion of ethylcholine aziridium (AF64A). In Morris water maze, AF64A-treated rats showed the delayed latencies to find the platform iron 6th day after the infusion. In pretrained rats, AF64A caused the significant delay of latency at 7th days but not 8th day. In the active avoidance for the pretrained rats, the escape latency was significantly delayed in AF64A-treatment. The percentages of avoidance in AF64A-treated rats were less increased than those in the control. Especially, the percentage of no response in the AF64A-treated rats was markedly increased in the first half trials. In the passive avoidance, AF64A-treated rats shortened the latency 1.5 h after the electronic shock, but not 24 h. AF64A also caused the pretrained rats to shorten the latency 7th day after the infusion, but not 8th day. These results indicate that AF64A might impair the learning and memory. However, these results indicate that the disturbed memory by AF64A might rapidly recover after the first retrain. Furthermore, these results suggest that AF64A may be a useful agent for the animal model of learning for Spatial cognition .
In the present study, we assessed the effects of white ginseng and red ginseng extract on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of ginseng extracts was investigated using the Morris water maze and Y-maze test. Drug-induced amnesia was induced by treating animals with scopolamine (2 mg/kg, i.p.), an antagonist of muscarinic acetylcholine (ACh) receptor. Tacrine was used a positive control. Ginseng extract (200 mg/kg, p.o.), tacrine (10 mg/kg, p.o.) administration significantly reduced the escape latency during training in the Morris water maze (p<0.05). At the probe trial session, scopolamine significantly increased the escape latency on day 5 in comparison with control (p<0.01). The effect of ginseng extracts on spontaneous alternation in Y-maze was similar to that of scopolamine treated group. In addition, numbers of arm entries were similar in all experimental groups. Moreover, red ginseng extract significantly inhibited acetylcholinesterase activity in the cortex and serum (p<0.05). Brain ACh contents of ginseng extract treated groups increased more than that of scopolamine group, which did not show statistically significant. These results suggest that ginseng extract may be useful for the treatment of cognitive impairment.
Lee Bom-Bi;Chung Jin-Yong;Kim Sun-Yeou;Kim Ho-Cheol;Kwon Youn-Jun;Hahm Dae-Hyun;Lee Hae-Jeong;Shim In-Sup
Korean Journal of Acupuncture
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v.19
no.2
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pp.63-78
/
2002
Kupunggibodan(KU), Gamisamul-tang(GA) and Whangryunhaedok-tang(WH) are clinically the most popular prescriptions as an herbal medicine in the treatment of ischemia. In order to compare and evaluate their protective effects on the ischema-induced cognitive deficits by middle cerebral artery occlusion (MCAO), we examined its ability to improve ischemia-induced cell loss and impairements of learning and memory in the Morris water maze and eight-arm radial arm maze. Focal cerebral ischemia produced a marked cell loss, decrease in acetylcholinesterase(AchE) reactivity in the hippocampus, and learning and memory deficits in two behavioral tasks. Pretreatment with WH (100 mg/kg, p.o.) produced a substantial increase in acquisition in the Morris water maze. Pretreatment with KU increased the perfomance of the resention test in the Morris water maze. WH, KU and GA caused a significant improvement in choice accuracy in radial arm maze test. WH was superior to KU and GA in perfomance of the radial arm maze test. Consistent with behavioral data, staining with cresyl violet showed that pretreatments with WH, but not KU and GA significantly recovered the ischemia-induced cell loss in the hippcampal CA1 area. In addition, pretreatments with WH and KU recovered the ischemia-induced reduction of AchE reactivity in the hippocampal CA1 area. These results demonstrated that KU, GA and WH have protective effects against ischimea-induced learning and memory impairments and that the efficacy was the order of WH>KU>GA in tratment of ischemia induced memory deficits. The present studies provide an evidence of KU, GA and WH as putative treatment of vascular dementia. Supported by a fund from the Ministry of Health and Welfare(HMP-00-OO-04-0004), and the Brain Korea 21 Project from Korean Ministry of Education, Korea.
This study was conducted to prove that there exists a relation between the spleen and learning and memory as Oriental medicine believesTo promote the function of the Spleen, Guibitang was administered to rats in this study. Rats were 250~300g Sprague-Dawley, and were divided into three groups. One was the normal group without any pretreatment. Another was the control group which was administered normal saline and the abdominal injection of L-NAME before learning and memory test. And the 3rd was the sample group, to which was administered Guibitang extract and (no 'the') abdominal injection of L-NAME before the learning and memory test. Each group was made up of 12 rats. Morris water maze and radial arm maze tasks were performed in the learning test and Morris water maze task in the memory test. For 2 days to evaluate the ability of learning in the Morris water maze, 16 trials were carried out and first latency(lapse time to find the escape platform for the first time) was measured. The next day, to evaluate the ability of memory, the escape platform was eliminated from the maze, and total path, target entry number, first latency and memory score were measured. 48hrs before the radial arm maze task was performed, bait was deprived from each group. After learning test, bait was permitted to each group. So 85% of the body weight was maintained for 6 days of the test. Each of the eight arms was baited; correct choice numer and error were counted; each trial was finished when the rat had entered each of the eight arms, or more than 10 minutes had elapsed. The results were as follows: In the learning test, the first latency of the sample group in the Morris water maze showed evident improvement of learning compared to control group at the 11th, 12th, 13th trial of 16 trials, and correct choice number in radial arm maze showed noticeable improvement compared to the control group at 3rd, 4th and 5th; In the memory test, the memory score of the sample group showed evident improvement compared to the control group. From the above results, the administration of Guibitang, which tonifies the function of the Spleen, could enhance the ability of learning and memory. So it was suggested that the Spleen has a relation with learning and memory.
Journal of Physiology & Pathology in Korean Medicine
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v.31
no.5
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pp.270-276
/
2017
The aim of this study was to investigate the effects of the water extract of Albizziae Cortex (AC) on the learning and memory impairments. AC was administered to normal mouse and scopolamine-injected amnesia mouse model. Passive avoidance test, Y-maze test, and Morris water maze test were conducted to confirm the cognitive-enhancing activities of AC. Acetylcholinesterase (AChE) activity and acetylcholine (Ach) content were measured after oral administration of AC. On the passive avoidance test, AC (200 mg/kg) significantly increased latency time and recovered scopolamine-impaired learning and memory in mice. In addition, AC (200 mg/kg) reduced Exploration time in target quadrant and reversed the scopolamine-induced cognitive impairments in the Y-maze test. Moreover, AC (200 mg/kg) increased exploration time in target quadrant and improved scopolamine-reduced escape latencies in the Morris water maze test. These effects were presented by regulatory effects of AC on AChE activity and Ach content. Taken together, AC increases cognitive-enhancing activities and ameliorates scopolamine-induced learning and memory impairment. AC might be a potential agent for prevention and treatment of amnesia and dementia.
The purpose of this study was to investigate the effects of the task-oriented training according to the application time with the change of motor and cognition function. Focal ischemic brain injury was produced in Sprague-Dawley rats (20 rats, $250{\pm}50$ g) through middle cerebral artery occlusion (MCAo). Before MCAo induction, all rats were trained in treadmill training and Morris water maze training for 1 week. Then they were randomly divided into groups: Group I : MCAo induction ($n_1$=5), Grop II: the application for simple treadmill task training after. MCAo induction ($n_2$=5). Group III: the application for Morris water maze cognitive task training after MCAo induction ($n_3$=5). Group IV: the application for progressive treadmill task training and Morris water maze cognitive task training after MCAo induction ($n_4$=5). Modified limb placing tests (MLPTs) and motor tests (MTs) were performed to test motor function and then Morris water maze acquisition test (MWMAT) and Morris water maze retention test (MWMRT) were performed to test cognitive function. For MTs, there were significant interactions among the groups with the time (p<.001). Group IV showed the steeper increasing pattern than those in other Groups on the 7th and 14th day. For MLPTs, there were significant interactions among the groups with the time (p<.001). The scores in Group III. IV had showed the more decreasing pattern than those in Group I, II since the 7th day and 14th day. For MWMAT, there were significant interactions among the groups with the time (p<.001). Group II found the Quadrant circular platform showed the steeper decreasing pattern than that in Group I on the 9th, 10th, 11th and 12th day. Group III. IV found the quadrant circular platform showed the slower decreasing pattern than that in Group I, II, For MWMRT, there were significant differences among the four groups (p<.001). The time to dwell on quadrant circular platform in Group IV on the 13th day was the longest compared with other groups. These results suggested that the combined task training was very effective to improve the motor and cognition function for the rats affected on their focal ischemic brain injury.
Jo Yun-Suk;Whang Wei-Wan;Kim Hyun-Taek;Park Soon-Kwon
Journal of Oriental Neuropsychiatry
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v.9
no.1
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pp.1-24
/
1998
The effects of Hyungbangjiwhangrang on the enhancement of learning and memory of AD model rats were studied with Morris water maze and radial arm maze. Sample group was electrolytically lesioned on nbM, and then daily treated with the medicine for two months. Control group with nbM lesion, and sham group with the sham operation were treated the vehicle for same duration. The following results were observed.1. As the learning trials of Morris water maze processed repeatedly, sham group achiened 201.64${\pm}$33.13 seconds in 1st trial, 153.14${\pm}$61.80 seconds in 2nd, 106.21${\pm}$46.81 seconds in 3rd, 76.64${\pm}$48.40 seconds in 4th, and 52.29${\pm}$38.25 seconds in 5th. The control group achieved 224.08${\pm}$29.16 in 1st trial, 191.77${\pm}$67.97 seconds in 2nd, 177.77${\pm}$65.44 seconds in 3rd, 140.92${\pm}$68.27 seconds in 4th, and 126.46${\pm}$79.15 seconds in 5th. The sample group achieved 223.36${\pm}$23.33 seconds in 1st trial, 215.86${\pm}$38.93 seconds in 2nd, 190.79${\pm}$51.57 seconds in 3rd, 155.79${\pm}$62.67 seconds in 4th, and 127.93${\pm}$62.11 seconds in 5th. Therefore, these data shows that all three groups were improved in learning capacity as trials were repeated, but the shame group showed prominent improvement in learning compared with the control group(p<0.05).2. In memory retention test of Morris water maze that counts the staying time in the target area, sham group stayed for 15.36${\pm}$5.39 seconds, the control group stayed for 5.54${\pm}$5.64 seconds, and the sample group stayed for 7.43${\pm}$6.09 seconds. The analysis of the memory retention data shows that the sham group marked more significant improvement stati- stically in memory retention compared with the control group(p<0.05).3. In the learning of radial arm maze, the number and rate of animals that arrive the learning criteria amounted 12 out of 14, 85.7% in sham group, 4 out of 13, 30.8% in the control group, and 10 out of 14, 71.4% in the sample group So, the sample group shows better learning capacity significantly compared with the control group(p<0.05). With the experimental results above, Hyungbangjiwhangtang can be supposed to have the improving effects on the learning and memory of AD rats induced by eletronical injury of nbM.
Journal of Physiology & Pathology in Korean Medicine
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v.25
no.4
/
pp.691-696
/
2011
In order to the neuroprotective effect of electroacupuncture (EA), the present study examined the effects of electroacupuncture inacupoint ST36 (Stomach 36) on trimethyltin chloride (TMT)-induced cognitive impairments rat using the Morris water maze (MWM) task and immunohistochemistry staining. The rats were randomly divided into the following groups: naive rat (Normal), TMT injection rat (Control), TMT injection + EA treated rat inacupoint ST36 (ST36) and TMT injection + EA treated rat in non-acupoint, base of tail (Non-AC). Electroacupuncture (2Hz, 2mA, and 10 minutes)was applied either to the acupuncture point ST36 or the nonacupuncture point in the tail for the last 14 days. In the water maze test, the animals were trained to find a platform in a fixed position during 4d and then received 60s probe trial on the $5^{th}$ day following removal of platform from the pool. Rats with TMT injection showed impaired learning and memory of the tasks and treatment with EA in acupoint ST36 (P<0.05) produced a significant improvement in escape latency to find the platform after $2^{nd}$ day and retention trial in the Morris water maze. Consistent with behavioral data, treatment with EA in acupoint ST36 also significantly increased expression of Choline acetyltransferase (ChAT) and Acetylcholinesterase (AChE) immunoreactive neurons in the hippocampus compared to the Control group. These results demonstrated that EA in acupoint ST36 has a protective effect against TMT-induced neuronal and cognitive impairments. The present study suggests that EA in acupoint ST36 might be useful in the treatment of TMT-induced learning and memory deficit.
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