Institute of Neurodegeneration and Neuroregeneration

Chuncheon, South Korea

Institute of Neurodegeneration and Neuroregeneration

Chuncheon, South Korea

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Kim S.K.,Sacred Heart College | Hwang I.K.,Seoul National University | Yoo K.-Y.,Institute of Neurodegeneration and Neuroregeneration | Bae E.,Sacred Heart College | And 3 more authors.
Brain Research | Year: 2010

Neural changes occur in the dam during gestation, and brain size has been shown to decrease across pregnancy in humans as well as rodents. In this study, we monitored neuronal damage, cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) at age-matched virgin control (17- to 18-week-old), gestation day (GD) 14.5, 16.5 and 18.5 (17- to 18-week-old dams), using NeuN for mature neurons, terminal deoxynucleotidyl dUTP nick-end labeling (TUNEL) and Fluoro-Jade B (F-J B) for neuronal death, Ki67 for cell proliferation and doublecortin (DCX) for neuroblast differentiation in C57BL/6 mice. There were no significant differences in NeuN-immunoreactive (+) neurons between the age-matched control and gestating groups. TUNEL or F-J B positive neurons were rarely detected in the DG in all the groups. Ki67+ cell proliferation was significantly decreased in the subgranular zone of the dentate gyrus (SZDG) at GD16.5. In addition, DCX+ neuroblasts with/without tertiary dendrites were decreased in the SZDG with gestation by GD16.5. However, in the GD18.5 group, the number of Ki67+ nuclei and DCX+ neuroblasts with/without tertiary dendrites was slightly increased compared to that observed at GD16.5. DCX protein levels were low at GD16.5, and thereafter slightly increased. These results suggest that cell proliferation and neuroblast differentiation in DG of the hippocampus is decreased during gestation. © 2009.


Lee C.H.,Institute of Neurodegeneration and Neuroregeneration | Moon S.M.,Sacred Heart College | Yoo K.-Y.,Institute of Neurodegeneration and Neuroregeneration | Choi J.H.,Institute of Neurodegeneration and Neuroregeneration | And 8 more authors.
Brain Research | Year: 2010

Delayed neuronal death following transient cerebral ischemia is mixed with apoptosis and necrosis, and the activation of microglia are activated after the ischemic insult. In the present study, we examined the long-term changes in neuronal degeneration and microglial activation in the gerbil hippocampal CA1 region after 5 min of transient cerebral ischemia using specific markers for neuronal damage and microliosis. Transient ischemia-induced neuronal death was shown in CA1 pyramidal cells 4 days after ischemia/reperfusion (I/R). However, neuronal degeneration of the pyramidal cells were observed up to 45 days in the CA1 region after I/R. Microglial activation was also observed in the CA1 region after I/R. Isolectin B4- (IB4) immunoreactive (+) microglia appeared in the CA1 region 4 days after I/R. On the other hand, ionized calcium-binding adapter molecule 1 (Iba-1)+ microglia was markedly increased after I/R, and peaked at 15 days after I/R. Thereafter, Iba-1 immunoreactivity was decreased with time-dependant manner in the ischemic CA1 region. These results indicate that neuronal degeneration of CA1 pyramidal cells may last about 45 days in the CA1 region after ischemic damage, and microglial activation may be diverse according to their function, such as phagocytosis, after I/R. © 2010 Elsevier B.V. All rights reserved.


Hwang I.K.,Seoul National University | Yi S.S.,Marquette University | Song W.,Seoul National University | Won M.-H.,Institute of Neurodegeneration and Neuroregeneration | Seong J.K.,Seoul National University
Brain Research | Year: 2010

In the present study, we investigated the effects of type 2 diabetes and treadmill exercise in chronic diabetic stages on neuroblast differentiation using doublecortin (DCX) in the subgranular zone of the dentate gyrus (SZDG) in Zucker diabetic fatty (ZDF) rats. Four-, 12-, 20- and 30-week-old Zucker lean control (ZLC) and ZDF rats were used to elucidate age-dependent changes of DCX-immunoreactive neuroblasts. DCX-immunoreactive neuroblasts were significantly decreased with age in the SZDG. This reduction was prominent in the age-matched ZDF rats compared to that in the ZLC rats. To investigate the effects of treadmill exercise, ZLC and ZDF rats at 23 weeks of age were put on the treadmill with or without running for 1 h/day/5 consecutive days at 12-16 m/min for 7 weeks. Treadmill exercise significantly increased the tertiary dendrites of DCX-immunoreactive neuroblasts in both ZLC and ZDF rats. In addition, exercise significantly increased the number of DCX-immunoreactive neuroblasts in the ZLC rats, but not in the ZDF rats. These results suggest that diabetes significantly decreases neuroblast differentiation and treadmill exercise in chronic diabetic animals has limitation to increase neuroblast differentiation although it increases neural plasticity. © 2009 Elsevier B.V. All rights reserved.


Hwang I.K.,Research Institute for Veterinary Science | Hwang I.K.,Seoul National University | Yi S.S.,Research Institute for Veterinary Science | Yi S.S.,Marquette University | And 12 more authors.
Brain Research | Year: 2010

Cyclooxygenase (COX) is a rate-limiting enzyme in synthesis of prostaglandins from arachidonic acid. In this study, we observed the effects of a physical exercise on COX-2 immunoreactivity in the hippocampus using immunohistochemistry in rats. In addition, we examined effects of administration of a COX-2 inhibitor, celecoxib, on neuroblast differentiation. At 6 weeks of age, Zucker lean control (ZLC) and Zucker diabetic fatty (ZDF) rats were put on a treadmill with or without running for 1 h/session/day for 5 weeks. The running speed was gradually increased from 16 to 22 m/min with 2 m/min per 2 weeks. In the ZLC and ZDF rats, COX-2 immunoreaction was detected in the granule cell layer of the dentate gyrus and in the stratum pyramidale of the CA2/3 region; COX-2 immunoreaction in the CA1 region was hardly detected. In the exercised-ZLC and ZDF rats, COX-2 immunoreactivity was significantly increased compared to that in the ZLC and ZDF rats, showing that COX-2 immunoreactivity in the exercised-ZDF rats was slightly low than that in the exercised-ZDF rats. In addition, weak COX-2 immunoreactivity was shown in the CA1 region by exercise. On the other hand, the repeated oral administration of celecoxib to 4-week-old ZDF rats significantly decreased the neuroblasts in the subgranular zone of the dentate gyrus. These results suggest that COX-2 may be associated with the increase of synaptic plasticity or contacts in the hippocampus. © 2010 Elsevier B.V. All rights reserved.


Lee C.H.,Institute of Neurodegeneration and Neuroregeneration | Choi J.H.,Institute of Neurodegeneration and Neuroregeneration | Yoo K.-Y.,Institute of Neurodegeneration and Neuroregeneration | Park O.K.,Institute of Neurodegeneration and Neuroregeneration | And 6 more authors.
Brain Research | Year: 2010

In the present study, we investigated the regulating effects of rosiglitazone (RSG), a synthetic agonist of peroxisome proliferator-activated receptor γ, treatment for 28 days on the cell proliferation and neuronal differentiation in the mouse hippocampal dentate gyrus by 5-bromo-2′-deoxyuridine (BrdU), Ki67 and doublecortin (DCX) immunohistochemistry. These markers were detected in the subgranular zone (SGZ) of the dentate gyrus in vehicle- and RSG-treated groups. In the RSG-treated group, the number of BrdU-, Ki67- and DCX-immunoreactive cells was significantly decreased compared to those in the vehicle-treated group. In addition, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor levels were significantly decreased in the dentate gyrus of the RSG-treated groups compared to the vehicle-treated group. These results indicate that RSG treatment decreases immunoreactivities of markers for cell proliferation and neuronal differentiation and levels of neurotrophic factors in the SGZ of the hippocampal dentate gyrus. © 2010 Elsevier B.V. All rights reserved.


Park O.K.,Institute of Neurodegeneration and Neuroregeneration | Yoo K.-Y.,Institute of Neurodegeneration and Neuroregeneration | Lee C.H.,Institute of Neurodegeneration and Neuroregeneration | Choi J.H.,Institute of Neurodegeneration and Neuroregeneration | And 5 more authors.
Journal of the Neurological Sciences | Year: 2010

Melatonin is synthesized from serotonin by the action of arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase. In this study, we observed cellular changes of arylalkylamine N-acetyltransferase (EC 2.3.1.87; AANAT) in the hippocampal CA1 region at various time points after ischemia/reperfusion. In vehicle-treated sham group, AANAT immunoreaction was detected in pyramidal neurons of the CA1 region. AANAT immunoreactivity in the neurons was highest 2 days and disappeared from 4 days after ischemia/reperfusion. From 3 days after ischemia/reperfusion, AANAT immunoreaction was expressed in astrocytes in the strata oriens and radiatum of the CA1 region. AANAT protein and mRNA levels were significantly increased 2 days after ischemia/reperfusion, and markedly decreased from 5 days after ischemia/reperfusion. The repeated administration of melatonin (10 mg/kg, i.p.) 3 times (once a day) to gerbils before ischemia/reperfusion significantly reduced ischemia-induced hyperactivity as well as neuronal death compared to those in the vehicle-treated ischemia group. Melatonin treatment also maintained AANAT immunoreactivity and its protein levels in the CA1 region after ischemia/reperfusion. These results suggest that the reduction of AANAT in ischemic CA1 region is associated with delayed neuronal death following transient ischemia, and melatonin treatment shows neuroprotection with maintenance of AANAT levels in the ischemic CA1 region. © 2010 Elsevier B.V. All rights reserved.


Lee J.-C.,Kangwon National University | Chen B.H.,Institute of Neurodegeneration and Neuroregeneration | Cho J.-H.,Kangwon National University | Kim I.H.,Kangwon National University | And 11 more authors.
Molecular Medicine Reports | Year: 2015

Inhibitors of DNA-binding/differentiation (ID) proteins bind to basic helix-loop-helix (bHLH) transcription factors, including those that regulate differentiation and cell-cycle progression during development, and regulate gene transcription. However, little is known about the role of ID proteins in the brain under transient cerebral ischemic conditions. In the present study, we examined the effects of ischemia-reperfusion (I-R) injury on the immunoreactivity and protein levels of IDs 1-4 in the gerbil hippocampus proper Cornu Ammonis regions CA1-3 following 5 min of transient cerebral ischemia. Strong ID1 immunoreactivity was detected in the nuclei of pyramidal neurons in the hippocampal CA1-3 regions; immunoreactivity was significantly changed following I-R in the CA1 region, but not in the CA2/3 region. Five days following I-R, ID1 immunoreactivity was not detected in the CA1 pyramidal neurons. ID1 immunoreactivity was detected only in GABAergic interneurons in the ischemic CA1 region. Weak ID4 immunoreactivity was detected in non-pyramidal cells, and immunoreactivity was again only changed in the ischemic CA1 region. Five days following I-R, strong ID4 immunoreactivity was detected in non-pyramidal cells, which were identified as microglia, and not astrocytes, in the ischemic CA1 region. Furthermore, changes in the protein levels of ID1 and ID4 in the ischemic CA1 region studied by western blot were consistent with patterns of immunoreactivity. In summary, these results indicate that immunoreactivity and protein levels of ID1 and ID4 are distinctively altered following transient cerebral ischemia only in the CA1 region, and that the changes in ID1 and ID4 expression may relate to the ischemia-induced delayed neuronal death.


Lee J.-C.,Kangwon National University | Tae H.-J.,Hallym University | Cho G.-S.,Korea University | Kim I.H.,Kangwon National University | And 11 more authors.
International Journal of Molecular Medicine | Year: 2015

Pyramidal neurons in region I of hippocampus proper (CA1) are particularly vulnerable to excitotoxic processes following transient forebrain ischemia. Kynurenic acid (KYNA) is a small molecule derived from tryptophan when this amino acid is metabolized through the kynurenine pathway. In the present study, we examined the effects of ischemic preconditioning (IPC) on the immunoreactivity and protein levels of KYNA following 5 min of transient forebrain ischemia in gerbils. The animals were randomly assigned to 4 groups (sham-operated group, ischemia-operated group, IPC + sham-operated group and IPC + ischemia-operated group). IPC was induced by subjecting the gerbils to 2 min of ischemia followed by 1 day of recovery. In the ischemia-operated group, we observed a significant loss of pyramidal neurons in the CA1 stratum pyramidale (SP) at 5 days post-ischemia; however, in the IPC + ischemia-operated group, the pyramidal neurons were well protected. KYNA immunoreactivity in the SP of the ischemia-operated group was significantly altered following ischemia-reperfusion and was very low 5 days following ischemia-reperfusion. In the IPC + ischemia-operated group, however, KYNA immunoreactivity was constitutively detected in the SP of the CA1 region after the ischemic insult. We also found that the alteration pattern of the KYNA protein level in the CA1 region following ischemia was generally similar to the immunohistochemical changes observed. In brief, our findings demonstrated that IPC maintained and even increased KYNA immunoreactivity in the SP of the CA1 region following ischemia-reperfusion. The data from the present study thus indicate that the enhancement of KYNA expression by IPC may be necessary for neuronal survival following transient ischemic injury.

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