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Neuroprotective effects of ischemic preconditioning on hippocampal CA1 pyramidal neurons through maintaining calbindin D28k immunoreactivity following subsequent transient cerebral ischemia

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Neural Regeneration Research 2017年第6期12卷 918-924页

作者： In Hye Kim Yong Hwan Jeon Tae-Kyeong Lee Jeong Hwi Cho Jae-Chul Lee Joon Ha Park Ji Hyeon Ahn bich-na shin Yang Hee Kim Seongkweon Hong Bing Chun Yan Moo-Ho Won Yun Lyul Lee Department of Neurobiology School of Medicine Kangwon National University Department of Radiology School of Medicine Kangwon National University Department of Biomedical Science Research Institute of Bioscience and Biotechnology Hallym University Department of Physiology College of Medicine Hallym University Department of Surgery School of Medicine Kangwon National University Institute of Integrative Traditional & Western Medicine Medical College Yangzhou University

Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning（2-minute transient cerebral ischemia） on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult（5-minute transient cerebral ischemia）. A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28 k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.

关键词： hippocampal subsequent minute pyramidal maintaining attenuated hippocampus neuronal occlusion fatal

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Effect of hyperthermia on calbindin-D 28k immunoreactivity in the hippocampal formation following transient global cerebral ischemia in gerbils

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Neural Regeneration Research 2017年第9期12卷 1458-1464页

作者： Jae-Chul Lee Jeong-Hwi Cho Tae-Kyeong Lee In Hye Kim Moo-Ho Won Geum-Sil Cho bich-na shin In Koo Hwang Joon Ha Park Ji Hyeon Ahn Il Jun Kang Young Joo Lee Yang Hee Kim Department of Neurobiology School of Medicine Kangwon National University Department of Pharmacology & Toxicology Shinpoong Pharmaceutical Co. Ltd. Department of Physiology College of Medicine Hallym University Department of Anatomy and Cell Biology College of Veterinary Medicine and Research Institute for Veterinary Science Seoul National University Department of Biomedical Science Research Institute of Bioscience and Biotechnology Hallym University Department of Food Science and Nutrition Hallym University Department of Emergency Medicine Seoul Hospital College of Medicine Sooncheonhyang University Department of Surgery School of Medicine Kangwon National University

Calbindin D-28K （CB）, a Ca2＋-binding protein, maintains Ca2＋ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is reported about the role of CB in the brain under hyperthermic condition during ischemic insults. We inves- tigated the effects of transient global cerebral ischemia on CB immunoreactivity as well as neuronal damage in the hippocampal formation under hyperthermic condition using immunohistochemistry for neuronal nuclei （NeuN） and CB, and Fluoro-Jade B histofluorescence staining in gerbils. Hyperthermia （39.5 ＋ 0.2~C） was induced for 30 minutes before and during transient ischemia. Hyperthermic ischemia resulted in neu- ronal damage/death in the pyramidal layer of CA1-3 area and in the polymorphic layer of the dentate gyrus at 1, 2, 5 days after ischemia. In addition, hyperthermic ischemia significantly decreaced CB immunoreac- tivity in damaged or dying neurons at 1, 2, 5 days after ischemia. In brief, hyperthermic condition produced more extensive and severer neuronal damage/death, and reduced CB immunoreactivity in the hippocampus following transient global cerebral ischemia. Present findings indicate that the degree of reduced CB immu- noreactivity might be related with various neuronal damage/death overtime and corresponding areas after ischemic insults.

关键词： nerve regeneration hyperthermic condition ischemia/reperfusion injury subregions of hippocampus delayed neuronal death calbindin D-28k neural regeneration

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Pretreated Oenan the Javanica extract increases anti-inflammatory cytokines, attenuates gliosis, and protects hippocampal neurons following transient global cerebral ischemia in gerbils

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Neural Regeneration Research 2019年第9期14卷 1536-1543页

作者： Joon Ha Park In Hye Kim Ji Hyeon Ahn YooHun Noh Sung-Su Kim Tae-Kyeong Lee Jae-Chul Lee bich-na shin Tae Heung Sim Hyun Sam Lee Jeong Hwi Cho In Koo Hwang Il Jun Kang Jong Dai Kim Moo-Ho Won Department of Biomedical Science and Research Institute for Bioscience and Biotechnology Hallym UniversityChuncheonGangwonRepublic of Korea Famenity Company GwacheonGeyonggiRepublic of Korea Department of Neurobiology School of MedicineKangwon National UniversityChuncheonGangwonRepublic of Korea Danchunok Company ChuncheonGangwonRepublic of Korea Department of Histology College of Veterinary MedicineChonbuk National UniversityIksanJeollabuk.doRepublic of Korea Department of Anatomy and Cell Biology College of Veterinary Medicineand Research Institute for Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea Department of Food Science and Nutrition Hallym UniversityChuncheonGangwonRepublic of Korea Division of Food Biotechnology School of BiotechnologyKangwon National UniversityChuncheonGangwonRepublic of Korea

Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ***,neuroprotective mechanisms of OJE have not been fully ***,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral *** treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral *** of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade *** of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,*** investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory *** we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 *** also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ***,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal *** findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 *** experimental plan of this study was rev

关键词： Oenanthe javanica extract transient global cerebral ischemia hippocampus ischemic damage cerebral ischemia neuroprotection glial activation pro-inflammatory cytokines anti-inflammatory cytokines inflammation neural regeneration

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Effect of ischemic preconditioning on antioxidant status in the gerbil hippocampal CA1 region after transient forebrain ischemia

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Neural Regeneration Research 2016年第7期11卷 1081-1089页

作者： Seung Min Park Chan Woo Park Tae-Kyeong Lee Jeong Hwi Cho Joon Ha Park Jae-Chul Lee Bai Hui Chen bich-na shin Ji Hyeon Ahn Hyun-Jin Tae Myoung Cheol shin Taek Geun Ohk Jun Hwi Cho Moo-Ho Won Soo Young Choi In Hye Kim Department of Emergency Medicine Sacred Heart HospitalCollege of MedicineHallym University Department of Emergency Medicine School of MedicineKangwon National University Department of Neurobiology School of MedicineKangwon National University Department of Physiology College of MedicineHallym University Department of Biomedical Science Research Institute of Bioscience and BiotechnologyHallym University

Ischemic preconditioning（IPC） is a condition of sublethal transient global ischemia and exhibits neuroprotective effects against subsequent lethal ischemic ***,in this study,examined the neuroprotective effects of IPC and its effects on immunoreactive changes of antioxidant enzymes including superoxide dismutase（SOD） 1 and SOD2,catalase（CAT） and glutathione peroxidase（GPX） in the gerbil hippocampal CA1 region after transient forebrain *** neurons of the stratum pyramidale（SP） in the hippocampal CA1 region of animals died 5 days after lethal transient ischemia without IPC（8.6%（ratio of remanent neurons） of the sham-operated group）;however,IPC prevented the pyramidal neurons from subsequent lethal ischemic injury（92.3%（ratio of remanent neurons） of the sham-operated group）.SOD1,SOD2,CAT and GPX immunoreactivities in the sham-operated animals were easily detected in pyramidal neurons in the stratum pyramidale（SP） of the hippocampal CA1 region,while all of these immunoreactivities were rarely detected in the stratum pyramidale at 5 days after lethal transient ischemia without ***,their immunoreactivities in the sham-operated animals with IPC were similar to（SOD1,SOD2 and CAT） or higher（GPX） than those in the sham-operated animals without ***,their immunoreactivities in the stratum pyramidale of the ischemia-operated animals with IPC were steadily maintained after lethal ischemia/*** of western blot analysis for SOD1,SOD2,CAT and GPX were similar to immunohistochemical *** conclusion,IPC maintained or increased the expression of antioxidant enzymes in the stratum pyramidale of the hippocampal CA1 region after subsequent lethal transient forebrain ischemia and IPC exhibited neuroprotective effects in the hippocampal CA1 region against transient forebrain ischemia.

关键词： hippocampal operated antioxidant stratum subsequent superoxide glutathione neuronal hippocampus peroxidase

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Oenanthe Javanica Extract Protects Against Experimentally Induced Ischemic Neuronal Damage via its Antioxidant Effects

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Chinese Medical Journal 2015年第21期128卷 2932-2937页

作者： Joon Ha Park Jeong Hwi Cho In Hye Kim Ji Hyeon Ahn Jae-Chul Lee Bai Hui Chen bich-na shin Hyun-Jin Tae Ki-Yeon Yoo SeongKweon Hong II Jun Kang Moo-Ho Won Jong-Dai Kim Department of Neurobiology School of Medicine Kangwon National University Chuncheon 200-701 South Korea Department of Physiology College of Medicine Hallym University Chuncheon 200-702 South Korea Department of Biomedical Science Research Institute of Bioscience and Biotechnology Hallym University Chuncheon 200-702 South Korea Department of Oral Anatomy College of Dentistry and Research Institute of Oral Science Gangneung-Wonju National University Gangneung 210-702 South Korea Department of Surgery School of Medicine Kangwon National University Chuncheon 200-701 South Korea Department of Food Science and Nutrition Hallym University Chuncheon 200-702 South Korea Division of Food Biotechnology School of Biotechnology Kangwon National University Chuncheon 200-701 South Korea

Background： Water dropwort （Oenanthejavanica） as a popular traditional medicine in Asia shows various biological properties including antioxidant activity. In this study, we firstly examined the neuroprotective effect of Oenanthejavanica extract （OJE） in the hippocampal comus ammonis 1 region （CA 1 region） of the gerbil subjected to transient cerebral ischemia. Methods： Gerbils were established by the occlusion of common carotid arteries for 5 min. The neuroprotective effect of OJE was estimated by cresyl violet staining. In addition, 4 antioxidants （copper, zinc superoxide dismutase [SOD], manganese SOD, catalase, and glutathione peroxidase） immunoreactivities were investigated by immunohistochemistry. Results： Pyramidal neurons in the CA1 region showed neuronal death at 5 days postischemia; at this point in time, all antioxidants immunoreactivities disappeared in CA1 pyramidal neurons and showed 100 mg/kg, OJE protected CA 1 pyramidal neurons from ischemic damage in many nonpyramidal cells. Treatment with 200 mg/kg, not In addition, 200 mg/kg OJE treatment increased or maintained antioxidants immunoreactivities. Especially, among the antioxidants, glutathione peroxidase immunoreactivity was effectively increased in the CA 1 pyramidal neurons of the OJE-treated sham-operated and ischemia-operated groups. Conclusion： Our present results indicate that treatment with OJE can protect neurons from transient ischemic damage and that the neuroprotective effect may be closely associated with increased or maintained intracellular antioxidant enzymes by OJE.

关键词： Antioxidant Enzymes Hippocampal Comus Ammonis 1 Region: Neuroprotection, Oenanthe Javanica Extract: TransientCerebral Ischemia

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Pretreated Glehnia littoralis Extract Prevents Neuronal Death Following Transient Global Cerebral Ischemia through Increases of Superoxide Dismutase 1 and Brain-derived Neurotrophic Factor Expressions in the Gerbil Hippocampal Cornu Ammonis 1 Area

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Chinese Medical Journal 2017年第15期130卷 1796-1803页

作者： Joon Ha Park Tae-Kveono Lee Bing-Chun Yan bich-na shin Ji Hyeon Ahn In Hye Kim Jeong Hwi Cho Jae-Chul Lee In Koo Hwang Jong Dai Kim Seongkweon Hong Young Joo Lee Moo-Ho Woll Il Jun Kang Department of Biomedical Science Research Institute of Bioscience and Biotechnology Hallym University Chuncheon 24252 Korea Department of Neurobiology School of Medicine Kangwon National University Chuncheon 24341 Korea Department of Traditional Chinese and Western Medicine Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases Yangzhou Jiangsu 225001 China Department of Physiology College of Medicine Hallym University Chuncheon 24252 Korea Department of Anatomy and Cell Biology College of Veterinary Medicine and Research Institute for Veterinary Science Seoul National University Seoul08826 Korea Division of Food Biotechnology School of Biotechnology Kangwon National University Chuncheon 24341 Korea Department of Surgery School of Medicine Kangwon National University Chuncheon 24341 Korea Department of Emergency Medicine Seoul Hospital College of Medicine Sooncheonhyang University Seoul 04401 Korea Department of Food Science and Nutrition Hallym University Chuncheon 24252 Korea

Background：Glehnia littoralis,as a traditional herbal medicine to heal various health ailments in East Asia,displays various therapeutic properties including antioxidant ***,neuroprotective effects of *** against cerebral ischemic insults have not yet been ***,in this study,we first examined its neuroprotective effects in the hippocampus using a gerbil model of transient global cerebral ischemia （TGCI）.Methods：Gerbils were subjected to TGCI for 5 *** extract （GLE;100 and 200 mg/kg） was administrated orally once daily for 7 days before ischemic *** was examined by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence *** was observed by immunohistochemistry for glial fibrillary acidic protein and ionized calcium-binding adapter molecule *** neuroprotective mechanisms,immunohistochemistry for superoxide dismutase （SOD） 1 and brain-derived neurotrophic factor （BDNF） was ***：Pretreatment with 200 mg/kg of GLE protected pyramidal neurons in the cornu ammonis 1 （CA1） area from ischemic insult area （F=29.770,P 〈 0.05） and significantly inhibited activationsof astrocytes （F =22.959,P 〈 0.05） and microglia （F =44.135,P 〈 0.05） in the ischemic CA1 *** addition,pretreatment with GLE significantly increased expressions of SOD1 （F =28.561,P 〈 0.05） and BDNF （F =55.298,P 〈 0.05） in CA1 pyramidal neurons of the sham-and ischemia-operated ***：Our findings indicate that pretreatment with GLE can protect neurons from ischemic insults,and we suggest that its neuroprotective mechanism may be closely associated with increases of SOD 1 and BDNF expressions as well as attenuation ofglial activation.

关键词： Antioxidant Gtial Activation Neurotrophic Factor Neuroprotection Pyramidal Neurons

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Effect of Oenanthe Javanica Extract on Antioxidant Enzyme in the Rat Liver

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Chinese Medical Journal 2015年第12期128卷 1649-1654页

作者： Choong-Hyun Lee Joon-Ha Park Jeong-Hwi Cho In-Hye Kim Ji-Hyeon Ahn Jae-Chul Lee Bai Hui Chen bich-na shin Hyun-Jin Tae Eun Joo Bae II-Jun Kang Moo-Ho Won Jong-Dai Kim Department of Pharmacy College of Pharmacy Dankook University Cheonan 330-714 South Korea Department of Neurobiology School of Medicine Kangwon National University Chuncheon 200-701 South Korea Department of Physiology College of Medicine Hallym University Chuncheon 200-702 South Korea Department of Biomedical Science Research Institute for Bioscience and Biotechnology Hallym University Chunchon 200-702 South Korea Department of Pediatrics Chuncheon Sacred Heart Hospital College of Medicine Hallym University Chuncheon 200-701 South Korea Department of Food Science and Nutrition Hallym University Chuncheon 200-702 South Korea Division of Food Biotechnology School of Biotechnology Kangwon National University Chuncheon 200-701 South Korea

Background：Oenanthe javanica （***） has been known to have high antioxidant properties via scavenging reactive oxygen *** examined the effect of *** extract （OJE） on antioxidant enzymes in the rat ***：We examined the effect of the OJE on copper,zinc-superoxide dismutase （SOD1）,manganese superoxide dismutase （SOD2）,catalase （CAT）,and glutathione peroxidase （GPx） in the rat liver using immunohistochemistry and western blot ***-Dawley rats were randomly assigned to three groups;（1） normal diet fed group （normal-group）,（2） diet containing ascorbic acid （AA）-fed group （AA-group） as a positive control,（3） diet containing OJE-fed group （OJE-group）.Results：In this study,no histopathological finding in the rat liver was found in all the experimental *** of SOD1,SOD2,CAT,and GPx immunoreactive cells and their protein levels were significantly increased in the AA-fed group compared with those in the *** the other hand,in the OJE-group,numbers of SOD1,SOD2,CAT,and GPx immunoreactive cells in the liver were significantly increased by about 190%,478%,685%,and 346%,respectively,compared with those in the *** addition,protein levels of SOD 1,SOD2,CAT,and GPx in the OJE-group were also significantly much higher than those in the ***：OJE significantly increased expressions of SOD 1 and SOD2,CAT,and GPx in the liver cells of the rat,and these suggests that significant enhancements of endogenous enzymatic antioxidants by OJE might be a legitimate strategy for decreasing oxidative stresses in the liver.

关键词： Antioxidant Enzymes Immunohistochemistry Liver Oenanthe Javanica Extract Western Blotting

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Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

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Neural Regeneration Research 2015年第6期10卷 944-950页

作者： Eun Joo Bae Bai Hui Chen Bing Chun Yan bich na shin Jeong Hwi Cho In Hye Kim Ji Hyeon Ahn Jae Chul Lee Hyun-Jin Tae Seongkweon Hong Dong Won Kim Jun Hwi Cho Yun Lyul Lee Moo-Ho Won Joon Ha Park Department of Pediatrics Chuncheon Sacred Heart HospitalCollege of MedicineHallym University Department of Physiology College of MedicineInstitute of Neurodegeneration and NeuroregenerationHallym University Institute of Integrative Traditional & Western Medicine Medical CollegeYangzhou University Department of Neurobiology School of MedicineKangwon National University Department of Biomedical Science and Research Institute for Bioscience and Biotechnology Hallym University Department of Surgery School of MedicineKangwon National University Department of Emergency Medicine Chuncheon Sacred Heart HospitalCollege of MedicineHallym University Department of Emergency Medicine School of MedicineKangwon National University

The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions （CA1-3） between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group, p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.

关键词： p53 tumor suppressor gene family cerebral ischemia/reperfusion pyramidal neurons CA1 region delayed neuronal death immunohistochemistry western blotting neural regeneration

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Monocarboxylate transporter 4 plays a significant role in the neuroprotective mechanism of ischemic preconditioning in transient cerebral ischemia

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Neural Regeneration Research 2015年第10期10卷 1604-1611页

作者： Seongkweon Hong Ji Yun Ahn Geum-Sil Cho In Hye Kim Jeong Hwi Cho Ji Hyeon Ahn Joon Ha Park Moo-Ho Won Bai Hui Chen bich-na shin Hyun-Jin Tae Seung Min Park Jun Hwi Cho Soo Young Choi Jae-Chul Lee Department of Surgery School of Medicine Kangwon National University Department of Emergency Medicine Sacred Heart Hospital College of Medicine Hallym University Department of Emergency Medicine School of Medicine Kangwon National University Department of Neuroscience College of Medicine Korea University Department of Neurobiology School of Medicine Kangwon National University Department of Physiology College of Medicine Hallym University Department of Biomedical Science Research Institute of Bioscience and Biotechnology Hallym University

Monocarboxylate transporters（MCTs）, which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning（IPC） on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups（sham-operated group, ischemia only group, IPC ＋ sham-operated group and IPC ＋ ischemia group）. A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region（CA1）, not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC ＋ ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC ＋ sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC ＋ ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia.

关键词： nerve regeneration monocarboxylate transporters ischemic preconditioning ischemia/ reperfusion injury hippocampus CA1 pyramidal neurons neural regeneration

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Glehnia fittoralis Extract Promotes Neurogenesis in the Hippocampal Dentate Gyrus of the Adult Mouse through Increasing Expressions of Brain-Derived Neurotrophic Factor and Tropomyosin-Related Kinase B

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Chinese Medical Journal 2018年第6期131卷 689-695页

作者： Joon Ha Park bich na shin Ji Hyeon Ahn Jeong Hwi Cho Tae-Kyeong Lee Jae-Chul Lee Yong Hwan Jeon II Jun Kang Ki-Yeon Yoo In Koo Hwang Choong Hyun Lee Yoo Hun Noh Sung-Su Kim Moo-Ho Won Jong Dai Kim Department of Biomedical Science and Research Institute for Bioscience and Biotechnology Hallym University Chuncheon 24252 Korea Department of Neurobiology School of Medicine Kangwon National University Chuncheon 24341 Korea Department of Radiology School of Medicine Kangwon National University Chuncheon 24341 Korea Department of Food Science and Nutrition Hallym University Chuncheon 24252 Korea epartment of Oral Anatomy College of Dentistry and Research Institute of Oral Biology Gangneung-Wonju National University Gangneung 25457 Korea Department of Anatomy and Cell Biology College of Veterinary Medicine and Research Institute for Veterinary Science Seoul National University Seou108826 Korea Department of Pharmacy College of Pharmacy Dankook University Cheonan 31116 Korea Famenity Biomedical Research Center Famenity Inc. Gyeonggi 13837 Korea Division of Food Biotechnology School of Biotechnology Kangwon National University Chuncheon 24341 Korea

Background： Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice. Methods： A total of 39 male ICR mice （12 weeks old） were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups （n = 13 in each group）. Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects ofG. litmralis extract, we performed immunohistochemistry tbr 5-bromo-2-deoxyuridine （BrdU, an indicator for cell proliferation） and doublecortin （DCX, an immature neuronal marker） and double immunofluorescence staining for BrdU and neuronal nuclear antigen （NeuN, a mature neuronal marker）. In addition, we examined expressional changes of brain-derived neurotrophic factor （BDNF） and its major receptor tropomyosin-related kinase B （TrkB） using Western blotting analysis. Results： Treatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive （＋） and DCX＋ cells （48.0 ±3.1and 72.0 ± 3.8 cells/section, respectively） in the subgranular zone （SGZ） of the dentate gyrus （DG） and BrdU＊/NeuN＋ cells （17.0 ±1.5 cells/section） in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and YrkB （about 232% and 244% of the vehicle-treated group, respectively） were significantly increased in the DG of the mice treated with 200 mg/kg ofG. littoralis extract. Conclusion： G. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases ofBDN F and TrkB proteins by G. littoralis extract treatment.

关键词： Brain-Derived Neurotrophic Factor CellProliferation Glehnia littoralis Neuroblast Differentiation Tropomyosin-Related Kinase B

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