Abnormal neurogenesis in the dentate gyrus of Goto-Kakizaki rat, a spontaneous model of type 2 diabetes. Implication of cerebrovascular remodeling and HPA axis disruption.

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

Buenos Aires, Argentina

Congreso; Congreso Iberoamericano de Neuroinmunomodulación; 2009

The International Society for NeuroImmunoModulation (ISNIM)

Diabetes is associated with central nervous system complications. Metabolic and vascular consequences of diabetes induce cognitive impairment and increase the risk of depression, stroke, and Alzheimer disease. The hippocampus is target of diabetic alterations. The dentate gyrus (DG) of the hippocampus is a neurogenic area being associated to memory and learning process. We explored hippocampal neurogenesis, and vascularisation, as a key component of the neurogenic microenvironment in a spontaneous model of T2D, the GK rat. HPA related parameters were studied. The number of proliferative Ki67+ DG cells was twice in GK than in Wistar (W) rats: 3309 ± 362 and 1496 ± 227, respectively. Neuronal maturation followed the same pattern. However, cell survival did not change between groups. The ratio vonWillebrand factor+ vessel area /DG area was decreased 50% in diabetics. GR immunolabelling in CA1 area decreased in GK exhibiting higher corticosterone levels. In the DG from GK rats we found increased cell proliferation and differentiation into neurons without changes in survival. Interestingly, high proliferation rate has been observed in brain trauma or ischemia and diseases like Alzheimer. Diabetes is correlated with augmented risk of cerebrovascular disease. Brain endothelium remodelling induced by chronic hyperglycemia/hyperlipidemia together with HPA axis disruption and insulin dysfunction in GK rats might be implicated in impaired DG neurogenesis.