Journal Article10.1007/S11064-009-0115-5
Metformin normalizes type 2 diabetes-induced decrease in cell proliferation and neuroblast differentiation in the rat dentate gyrus
In Koo Hwang,Il Yong Kim,Eun Jung Joo,Jae Hoon Shin,Ji Won Choi,Moo Ho Won,Yeo Sung Yoon,Je Kyung Seong +7 more
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TL;DR: It is suggested that diabetes significantly reduces cell proliferation and neuroblast differentiation in the SZDG in diabetic rats and that metformin treatment normalizes the reduction of cell proliferation
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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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Citations
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References
•Book
The Rat Brain in Stereotaxic Coordinates
George Paxinos,Charles Watson +1 more
- 01 Jan 1983
TL;DR: This paper presents a meta-analyses of the determinants of earthquake-triggered landsliding in the Czech Republic over a period of 18 months in order to establish a probabilistic framework for estimating the intensity of the earthquake.
60.4K
Role of AMP-activated protein kinase in mechanism of metformin action
Gaochao Zhou,Robert W. Myers,Ying Li,Yuli Chen,Xiaolan Shen,Judy Fenyk-Melody,Margaret Wu,John Ventre,Thomas W. Doebber,Nobuharu Fujii,Nicolas Musi,Michael F. Hirshman,Laurie J. Goodyear,David E. Moller +13 more
TL;DR: It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.
TL;DR: It is demonstrated that DCX is expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development and likely directs neuronal migration by regulating the organization and stability of microtubules.
1.3K
Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons.
Fiona Francis,Annette Koulakoff,Dominique Boucher,Philippe Chafey,Bruce T. Schaar,M C Vinet,Gaëlle Friocourt,Nathalie McDonnell,Orly Reiner,Axel Kahn,Susan K. McConnell,Yoheved Berwald-Netter,Philippe Denoulet,Jamel Chelly +13 more
TL;DR: It is shown that Doublecortin is expressed in the brain throughout the period of corticogenesis in migrating and differentiating neurons, and Immunohistochemical studies show its localization in the soma and leading processes of tangentially migrating neuron, and a strong axonal labeling is observed in differentiating neuron.
1K
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