Increased hippocampal neurogenesis in a aspontaneous 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; 44 th Annual Meeting of the European Association for the Study of Diabetes; 2008

European Association for the Study of Diabetes

  Print this Page for Your Records Close Window Title: Increased hippocampal neurogenesis in a spontaneous model of type 2 diabetes (T2D), the Goto-Kakizaki (GK) rat Presenter: F.E. Saravia1, J. Beauquis1, J. Coulaud2, P. Roig1, B. Portha2, F. Homo-Delarche2, A.F. De Nicola1; 1Neuroendocrine Biochemistry, Institute of Biology and Experimental Medicine, Buenos Aires, Argentina, 2Cnrs umr 7059, Paris-Diderot University, Paris, France. Presentation Number: 1393 Background and aims: 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<0.02. BrdU+ cell number -indicator of cell survival- was slightly increased in GK vs W. Neuronal maturation of new DG cells followed the same pattern: DCX+ cells were twice as much in diabetic animals as compared to controls: 15776 ± 745.3 and 9923 ± 1356 respectively, p<0.01. Finally, the ratio vWF+ vessel area /DG area was decreased by more than 50% in diabetic animals: GK: 0.033 ± 0.004, W: 0.078 ± 0.013, p<0.05.Conclusion: A net increase in hippocampal neurogenesis, together with increased cell proliferation and survival, was observed in type 2 diabetic GK rats. Interestingly, high neurogenesis rates have been observed in pathological situations, such as brain trauma, seizures and ischemia and diabetes is correlated with augmented risk of cerebrovascular disease. Macro- and microangiopathy have been described in GK rats in the cerebrovasculature and the islet of Langerhans, respectively. Therefore, cerebrovascular remodelling induced by chronic hyperglycemia/hyperlipidemia in GK rats might be responsible for their high DG neurogenesis, as corroborated by our data showing a markedly diminished blood vessel area.   OASIS - Online Abstract Submission and Invitation System™ ©1996-2009, Coe-Truman Technologies, Inc.