Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes
Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes
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DOI：
10.1016/j.bbr.2008.11.001
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发表时间：
2009-03-02
影响因子：
2.7
通讯作者：
Saravia, Flavia
中科院分区：
文献类型：
--
作者：
Alvarez, Edgardo O.;Beauquis, Juan;Saravia, Flavia
1型糖尿病（T1D）伴有“糖尿病性脑病”，包括对压力过敏、中风、痴呆和认知障碍的风险增加。在之前的研究中，我们报道了自发性和链脲佐菌素诱导的实验性T1D模型的一些大脑改变，包括海马增殖和存活的强烈减少。本研究的目的是探讨链脲佐菌素治疗小鼠齿状回轻度神经退行性变的相关参数及其与行为改变的潜在相关性。通过双皮质素（DCX）表达测量的神经源性状态显示，亚颗粒区（SGZ）阳性细胞数量显著下降。然而，神经元迁移不受影响。我们发现细胞内脂褐质沉积明显增强，这是氧化应激和衰老增加的特征，在门、SGZ和颗粒细胞层（GCL）中都是如此。糖尿病小鼠在学习和记忆测试中表现出明显的损伤，与对照组小鼠相比，表现出更高的逃避反应潜伏期和更低的主动回避反应学习效率。在不对称升高+迷宫中，在冲突环境中的探索性和非探索性活动均不受糖尿病状况的影响。总之，实验糖尿病患者在齿状回中表现出明显的变化迹象，这种变化与衰老过程中出现的变化相似。相对而言，这些变化与学习和记忆测试中的表现下降是一致的。神经紊乱和行为紊乱之间的潜在联系机制还没有被完全理解。(C) 2008 Elsevier B.V.版权所有
Type 1 diabetes (T1D) is accompanied by a "diabetic encephalopathy" including hypersensitivity to stress, increased risk of stroke, dementia and cognitive impairment.In previous works we reported several brain alterations including a strong decrease in hippocampal proliferation and survival in both spontaneous and streptozotocin-induced models of experimental T1D. The aim of this study was to explore in streptozotocin-treated mice and other parameters associated to mild neurodegeneration in the dentate gyrus and the potential correlation with behavioural changes. The neurogenic status, measured by doublecortin (DCX) expression, showed an important decline in the number of positive cells in the subgranular zone (SGZ). However, neuronal migration was not affected. We found a marked enhancement of intracellular lipofuscin deposits, characteristic of increased oxidative stress and aging in both, the hilus and the SGZ and granular cell layer (GCL). Diabetic mice showed a significant impairment in learning and memory tests, exhibiting a higher latency to show an escape response and a poorer learning efficiency of an active avoiding response compared with control mice. Both, exploratory and non-exploratory activities in a conflictive environment in the asymmetric elevated plus maze were not affected by the diabetic condition. In conclusion, experimental diabetes showed clear signs of changes in the dentate gyrus, changes similar to those present in the aging process. Correlatively, these alterations were in line with a reduced performance in learning and memory tests. The mechanism that could potentially link neural and behavioural disturbances is not yet fully comprehended. (C) 2008 Elsevier B.V. All rights reserved.