Increased hippocampal neurogenesis in a spontaneous model of type 2 diabetes (T2D), the Goto-Kakizaki (GK) rat.

SARAVIA F; BEAUQUIS J; COULAUD J; ROIG P; PORTHA B; HOMO-DELARCHE F; DE NICOLA, AF

Roma, Italia

Congreso; Congreso Internacional de la European Association for the Study of Diabetes (EASD); 2008

European Association for the Study of Diabetes

Background/aim: Diabetes, regardless of the type, is associated with central nervous system (CNS) complications. Indeed, metabolic and vascular consequences of diabetes induce cognitive impairment and increase the risk of depression, stroke, dementia and Alzheimer disease. The hippocampus, part of the limbic system, is a particular CNS target of diabetic alterations, both in patients and animal models. More precisely, the dentate gyrus (DG) of the hippocampus is one of the rare brain areas, where new neurons -associated to memory and learning process- are generated during adulthood. We previously showed that adult hippocampal neurogenesis is altered in animal models of type 1 diabetes. Here, we explored hippocampal neurogenesis, and vascularisation, as a key component of the neurogenic microenvironment in a spontaneous model of T2D, the GK rat. Materials and Methods: Four-month-old GK and control male Wistar (W) rats were used, n=4-5. Bromodeoxyuridine (BrdU, 250 mg/k BW) was administered i.p. 21 days before cardiac perfusion with 3% paraformaldehyde. DG containing brain sections (vibratome) were used for immunohistochemistry with the following markers: 1) Ki67 (cellular proliferation); 2) BrdU (cell survival); 3) doublecortin (DCX, neuronal differentiation); and 4) von Willebrand factor (vWF, endothelium). Data were evaluated by computer-assisted image analysis. Results: The number of proliferative Ki67+ DG cells was twice in GK than in W rats: 3309 ± 362 and 1496 ± 227, respectively, p