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Ameliorating Effects of Cheongnoemyeongsin-hwan on Learning and Memory Impairment Induced by Cerebral Hypoperfusion in Rats (청뇌명신환(淸腦明神丸)이 뇌혈류저하 흰쥐의 학습 및 기억 장애 개선에 미치는 영향)

  • Chang, Suk Hee;Hwang, Won Deuk
    • Herbal Formula Science
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    • v.25 no.1
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    • pp.69-87
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    • 2017
  • Objectives : Cheongnoemyeongsin-hwan (CNMSH) is a herb medicine to treat cognitive impairment. This study was investigated the effects of CNMSH on learning and memory impairment induced by cerebral hypoperfusion. Cerebral hypoperfusion was produced chronically by permanent bilateral common carotid artery occlusion (BCCAO) in rats. Methods : CNMSH was administered orally once a day (250 mg/kg) for 28 days starting at 4th week after the BCCAO. The acquisition of learning and the retention of memory were tested on 9th week after the BCCAO using the Morris water maze. In addition, effect of CNMSH on neuronal apoptosis and ${\beta}-amyloid$ accumulation in the hippocmapus was evaluated with immunohistochemistry and Western blotting. Results : 1. CNMSH and ChAL significantly shortened the escape latencies on the 2nd day of acquisition training trials. 2. ChAL significantly prolonged the swimming time spent in the target and peri-target zones and CNMSH also significantly prolonged the swimming time spent in the peri-target zone. 3. CNMSH and ChAL significantly increased the number of target heading in the retention test. 4. ChAL significantly shortened the time of the 1st target heading in the retention test, but CNMSH insignificantly shortened the time of that. 5. CNMSH and ChAL significantly increased the memory score in the retention test. 6. CNMSH and ChAL significantly attenuated the reduction of CA1 neurons, but insignificantly attenuated the reduction of CA1 thickness. 7. CNMSH and ChAL significantly attenuated the up-regulation of Bax expression in the CA1 of hippocampus. 8. CNMSH and ChAL significantly attenuated the up-regulation of cascapse-3 expression in the CA1 of hippocampus. 9. CNMSH and ChAL significantly attenuated the ${\beta}-amyloid$ accumulation in the CA1 of hippocampus. 10. CNMSH and ChAL significantly attenuated the up-regulation of APP expression in the CA1 of hippocampus. 11. CNMSH and ChAL significantly attenuated the up-regulation of BACE-1 expression in the CA1 of hippocampus. Conclusions : The results show that CNMSH attenuates neuronal apoptosis and ${\beta}-amyloid$ accumulation in the hippocampus and alleviates the impairment of learning and memory produced by chronic cerebral hypoperfusion. These results suggest that CNMSH may be a beneficial medicinal herb to treat cognitive impairment associated with neurodegenerative diseases.

Effects of Preconceptional Ethanol Consumption on ADHD-Like Symptoms in Sprague-Dawley Rat Offsprings

  • Choi, In-Ah;Kim, Pitna;Joo, So-Hyun;Kim, Min-Kyeong;Park, Jin-Hee;Kim, Hee-Jin;Ryu, Jong-Hoon;Cheong, Jae-Hoon;Shin, Chan-Young
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.226-233
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    • 2012
  • Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investigated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat.

Anti-amnesic and Neuroprotective Effects of Artemisia argyi H. (Seomae mugwort) Extracts (섬애쑥 추출물의 뇌 신경세포 보호효과에 의한 학습 및 기억능력 개선 효과)

  • Ha, Gi-Jeong;Lee, Doo Sang;Seung, Tae Wan;Park, Chang Hyeon;Park, Seon Kyeong;Jin, Dong Eun;Kim, Nak-Ku;Shin, Hyun-Yul;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.47 no.3
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    • pp.380-387
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    • 2015
  • The anti-amnesic effect of Artemisia argyi H against trimethyltin (TMT)-induced learning and memory impairment and its neuroprotective effect against $H_2O_2$-inducedoxidative stress were investigated. Cognitive behavior was examined by Y-maze and passive avoidance test for 4 weeks, which showed improved cognitive functions in mice treated with the extract. In vitro neuroprotective effects against $H_2O_2$-induced oxidative stress were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide and lactate dehydrogenase (LDH) assays. A. argyi H. extract showed protective effects against $H_2O_2$-induced neurotoxicity; moreover, LDH release into the medium was inhibited. Finally, high-performance liquid chromatography (HPLC) analysis showed that eupatilin and jaceosidin were the major phenolic compounds in A. argyi H. extract. These results suggest that A. argyi H. could be a good source of functional substances to prevent neurodegenerative diseases.

Protective Effects of Black Soybean Seed Coat Extracts against Oxidative Stress-induced Neurotoxicity (산화적 손상에 의해 유도된 신경세포독성에 대한 검정콩 껍질 추출물의 보호효과)

  • Kwak, Ji Hyeon;Jo, Yu Na;Jeong, Ji Hee;Kim, Hyeon Ju;Jin, Su Il;Choi, Sung-Gil;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.45 no.2
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    • pp.257-261
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    • 2013
  • Rat pheochromocytoma cells (PC12) and mice were utilized as in vitro and in vivo models to determine the neuroprotective effects of a 70% acetone extract of black soybean seed coat (BSSCE). BSSCE showed higher total phenolic contents than other extracts. Intracellular reactive oxygen species accumulation from $H_2O_2$ treatment of PC12 cells was significantly reduced when BSSCE was present in the media compared to PC12 cells treated with $H_2O_2$ only. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide (MTT) reduction assay and lactate dehydrogenase assay also showed significantly increased protective effects in PC12 cells. In addition, BSSCE improved the in vivo cognitive ability against amyloid beta peptide-induced neuronal deficits.

A Study on the Effect of Prefrontal EEG-Neurofeedback on Development of Infants' Brain Function and Intelligence (전전두엽 EEG-뉴로피드백 훈련과 유아의 뇌기능 및 지능발달에 대한 연구)

  • Jang, Soon-Ok;Yi, Seon-Gyu
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.10 no.6
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    • pp.1317-1328
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    • 2009
  • As a study on how the Neurofeedback training effects on young children's brain function and intelligence, first, this paper aims to verity the effect Neurofeedback training brings to the function of young children's brain. Second, through K-WPPSI IQ test, analyses how Neurofeedback training influences on the development of young children's intelligence. The subjects of this study were the 60 five-year children attenging J kindergarten in Cheon-an, experimnet treatment was performed according to Neurofeedback training guidance from Aprile 21 to December 12, 2008. It analyzes the states of brain waves before and after the Neurofeedback training, and performed the statistical analysis through t-test, using SPSS for Window(V.13.0) package. As a result of analysis, it was shown that firstly Neurofeedback training was very effective on the d!evelopment of infan's brain intelligence, since the quotient to evaluate the entire brain function appeared to have a meaningful influence. Secondly, it was proved that Neurofeedback training had much influence on the object assembly-area, the maze-area, and picture completion-area, and that it had the same influence on the performance intelligence quotient too. So, such results as these one make us realize that Neurofeedback training is a very effective method to the development of performance intelligence quotient. Thirdly, they indicate that Neurofeedback training hasn't a meaningful influence on verbal intelligence quotient, since it affects only on the similarities area among verbal intelligence quotient, the total evaluative quotient.

Ginseng improves cognitive deficit via the RAGE/NF-κB pathway in advanced glycation end product-induced rats

  • Tan, Xiaobin;Gu, Junfei;Zhao, Bingjie;Wang, Shuyuan;Yuan, Jiarui;Wang, Chunfei;Chen, Juan;Liu, Jiping;Feng, Liang;Jia, Xiaobin
    • Journal of Ginseng Research
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    • v.39 no.2
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    • pp.116-124
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    • 2015
  • Background: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. Methods: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-${\kappa}B$). Results: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-${\kappa}B$. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. Conclusion: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-${\kappa}B$ pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

GABA-enriched fermented Laminaria japonica improves cognitive impairment and neuroplasticity in scopolamine- and ethanol-induced dementia model mice

  • Reid, Storm N.S.;Ryu, Je-kwang;Kim, Yunsook;Jeon, Byeong Hwan
    • Nutrition Research and Practice
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    • v.12 no.3
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    • pp.199-207
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    • 2018
  • BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.

Theracurmin Ameliorates Cognitive Dysfunctions in 5XFAD Mice by Improving Synaptic Function and Mitigating Oxidative Stress

  • Kim, Jihyun;Kim, Jaehoon;Huang, Zhouchi;Goo, Nayeon;Bae, Ho Jung;Jeong, Yongwoo;Park, Ho Jae;Cai, Mudan;Cho, Kyungnam;Jung, Seo Yun;Bae, Soo Kyung;Ryu, Jong Hoon
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.327-335
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    • 2019
  • As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.

Comparison of scopolamine-induced cognitive impairment responses in three different ICR stocks

  • Yoon, Woo Bin;Choi, Hyeon Jun;Kim, Ji Eun;Park, Ji Won;Kang, Mi Ju;Bae, Su Ji;Lee, Young Ju;Choi, You Sang;Kim, Kil Soo;Jung, Young-Suk;Cho, Joon-Yong;Hwang, Dae Youn;Song, Hyun Keun
    • 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.

Effect of Fermented Garlic Extract Containing Nitric Oxide Metabolites on Impairments of Memory and of Neural Plasticity in Rat Model of Vascular Dementia (산화질소 대사체 함유 마늘 발효 추출물 이용 혈관성 치매 흰쥐 모델의 기억력 및 신경가소성 장애 개선 효과)

  • Zhang, Xiaorong;Moon, Se Jin;Kim, Yoo Ji;Jeong, Sun Oh;Kim, Min Sun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.36 no.2
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    • pp.59-65
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    • 2022
  • Rodent model for chronic cerebral hypoperfusion caused by bilateral carotid artery occlusion (BCAO) show clinically relevant evidences for vascular dementia and impairments of synaptic plasticity in the hippocampus. The purpose of this study was to evaluate effect of fermented garlic (F-Garlic) extract with NO metabolites on cognitive behaviors, synaptic plasticity, and molecular events in the hippocampus following BCAO. Adult male Sprague-Dawley rats were randomly divided three experimental groups into: control+water; BCAO+water; BCAO+F-Garlic. Animals were treated with oral administration of F-Garlic in tap water as a drinking water after surgery for 4 weeks. On passive avoidance test and Y-maze test, BCAO+water showed a significant decrease in step-through latency and spontaneous alteration, indicating deficit of hippocampal memory formation but the treatment of F-Garlic significantly increased these cognitive behaviors. In control+water, a robust increase in the amplitude of evoked field excitatory postsynaptic potentials was observed by theta burst stimulation to hippocampal neural circuit indicating formation of long-term potentiation (LTP) in the hippocampal CA1. BCAO+water showed a highly significant deficit in LTP induction 4 weeks after BCAO. On other hand, daily oral administration of F-Garlic extract caused the marked preservation of LTP induction. Moreover, parvalbumin was markedly reduced in the CA1, especially, in the stratum radiatum of BCAO+water. In contrast, BCAO+F-Garlic mitigate a significantly reduction of the parvalbumin. In summary, these results suggest that daily oral administration of F-Garlic extract can ameliorate cognitive memory deficit through the preservation of synaptic plasticity and interneurons integrity in the hippocampus in rodent model of chronic cerebral hypoperfusion.