Metformin Normalizes Type 2 Diabetes-Induced Decrease in Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus |
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| Authors: | In Koo Hwang Il Yong Kim Eun Jung Joo Jae Hoon Shin Ji Won Choi Moo-Ho Won Yeo Sung Yoon Je Kyung Seong |
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| Institution: | (1) Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea;(2) Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea;(3) Interdisciplinary Program in Brain Science, Seoul National University, Seoul, 151-742, South Korea;(4) Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea;(5) Interdisciplinary Program for Bioinformatics, Seoul National University, Seoul, 151-742, Korea;(6) Program for Cancer Biology, Cancer Research Institute, College of Medicine, Seoul National University, Seoul, 151-742, Korea; |
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| Abstract: | In this study, we observed the effects of metformin, one of the most widely prescribed drugs for the treatment of type 2 diabetes,
on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus (SZDG) in Zucker
diabetic fatty (ZDF) rats, which are a model for type 2 diabetes. For this, metformin was administered orally once a day to
14-week-old ZDF rats for 2 weeks and the animals were sacrificed at 16 weeks of age. During this period, blood glucose levels
were higher in the vehicle-treated ZDF rats than in the Zucker lean control (ZLC) rats. Metformin treatment significantly
decreased the blood glucose levels from 15.5 weeks of age. In the SZDG, Ki67 (a marker for cell proliferation)- and doublecortin
(DCX, a marker for differentiated neuroblasts)-immunoreactive cells were much lower in the vehicle-treated ZDF rats than in
the ZLC rats. In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG
compared to those in the vehicle-treated ZDF group. These results suggest that diabetes significantly reduces cell proliferation
and neuroblast differentiation in the SZDG and that metformin treatment normalizes the reduction of cell proliferation and
neuroblast differentiation in the SZDG in diabetic rats. |
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