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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.


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.


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 | 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.


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.

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