Impaired neurogenesis in adult type-2 diabetic rats.
Type-2 diabetes is an adult onset condition that affects millions of people worldwide. The ensuing hyperglycemia renders multiple organs to various complications and increases the risk of learning and memory impairment. The Goto-Kakizaki (GK) rat developed from normoglycemic Wistar-Kyoto (WKY) rat is a model for type-2 diabetes, with insulin resistance developing around 12 weeks of age. We presently analyzed the neural progenitor proliferation and survival of the newly generated cells in the dentate gyrus (DG) and the subventricular zone (SVZ) of 6 and 18 week-old GK and WKY rats. At 6 weeks of age, both GK and WKY cohorts showed similar blood glucose levels (112+/-14 mg/dL) and similar rates of neural progenitor proliferation. At 18 weeks of age, the GK rats showed significantly increased blood glucose levels (by 92+/-12%; p<0.05) and higher number of proliferating neural progenitor cells compared to WKY rats (by 183+/-16% in SVZ and by 36+/-5% in DG; p<0.05 in both cases). In both the neurogenic areas, 52+/-9% of the newly formed cells survived to 3 weeks in the 18 weeks old WKY rats, but in the GK rats only 16+/-7% of the new cells survived to 3 weeks. When cultured from the DG of the 18 week old rats in the presence of FGF2 and IGF1, the GK cohort yielded significantly lower number of neurospheres than the WKY cohort (by 69+/-7%; p<0.05). These results indicate that hyperglycemic environment induces proliferation of adult neural progenitors, but detrimental to their survival. Impaired neurogenesis might be a promoter of the decreased brain function in type-2 diabetes.
Lang
Bradley T
BT
Department of Neurological Surgery, University of Wisconsin K4/8 Mail code CSC 8660 600 Highland avenue Madison, WI 53792, USA.
Yan
Yiping
Y
Dempsey
Robert J
RJ
Vemuganti
Raghu
R
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001973:Bromodeoxyuridine; D002470:Cell Survival; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006943:Hyperglycemia / Q000503:physiopathology; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020547:Lateral Ventricles / Q000503:physiopathology; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013234:Stem Cells / Q000502:physiology
D001786:Blood Glucose; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D001973:Bromodeoxyuridine