Hippocampal neurovascular and hypothalamic-pituitary-adrenal axis alterations in spontaneously type 2 diabetic GK rats
Hippocampal neurovascular and hypothalamic-pituitary-adrenal axis alterations in spontaneously type 2 diabetic GK rats
复制标题
DOI：
10.1016/j.expneurol.2009.12.022
复制
发表时间：
2010-03-01
影响因子：
5.3
通讯作者：
Saravia, Flavia
中科院分区：
文献类型：
--
作者：
Beauquis, Juan;Homo-Delarche, Francoise;Saravia, Flavia
糖尿病的代谢和血管后果诱导几种CNS并发症。海马齿状回是糖尿病改变的公认靶点，是与记忆和学习过程相关的神经原性区域。在这里，我们探讨了海马神经发生和它的微环境（星形胶质细胞，血管化和糖皮质激素的影响）在2型糖尿病的自发模型，后藤Kakizaki大鼠。在4月龄时，糖尿病大鼠海马中增殖的Ki 67（+）细胞和年轻的doublecortin（+）神经元的数量是正常血糖对照Wistar大鼠的2倍。然而，在溴脱氧尿苷给药后3周，细胞存活率没有差异。血管性血友病因子对内皮细胞的标记显示，糖尿病大鼠血管覆盖的颗粒细胞层分数面积减少50%，毛细血管分支减少。最后，后藤Kakizaki大鼠表现出减少糖皮质激素受体免疫标记CAI，与较高的皮质酮血症。总之，糖尿病大鼠表现出细胞增殖和神经元分化增加，而没有伴随的生存改变。高增殖率可能反映了神经元痛苦的补偿机制，也存在于各种病理情况中。然而，慢性高血糖，高瘦素血症和胰岛素抵抗诱导的内皮细胞改变，并与有害的糖皮质激素的影响可能会损害有效的神经发生在糖尿病Goto-Kakizaki大鼠。(C)2009 Elsevier Inc. All rights reserved.
Metabolic and vascular consequences of diabetes mellitus induce several CNS complications. The dentate gyrus of the hippocampus, a well-recognized target for diabetic alterations, is a neurogenic area associated with memory and learning processes. Here, we explored the hippocampal neurogenesis and its microenvironment (astrocytes, vascularisation and glucocorticoid influence) in a spontaneous model of type 2 diabetes, the Goto-Kakizaki rat. The number of proliferative Ki67(+) cells and young doublecortin(+) neurons was 2-fold higher in the hippocampus from diabetic rats than in normoglycemic control Wistar at 4 months of age. However, there was no difference in cell survival, studied 3 weeks after bromodeoxyuridine administration. Labeling of endothelial cells against von Willebrand factor, demonstrated a 50% decrease in the granular cell layer fractional area covered by blood vessels and a diminished capillary branching in diabetic rats. Finally, Goto-Kakizaki rats exhibited decreased glucocorticoid receptor immunolabeling in CAI, associated with higher corticosteronemia. In conclusion, diabetic rats showed increased cell proliferation and neuronal differentiation without concomitant survival modification. A high proliferation rate, potentially reflecting a compensatory mechanism for neuronal suffering, also exists in various pathological situations. However, endothelial alteration induced by chronic hyperglycemia, hyperleptinemia and insulin resistance and associated with deleterious glucocorticoid effects might impair effective neurogenesis in diabetic Goto-Kakizaki rats. (C) 2009 Elsevier Inc. All rights reserved.