Alvarez Edgardo O, Beauquis Juan, Revsin Yanina, Banzan Arturo M, Roig Paulina, De Nicola Alejandro F, Saravia Flavia
Pharmacology Area, Medical Sciences Faculty, National University of Cuyo, Mendoza, Argentina.
Behav Brain Res. 2009 Mar 2;198(1):224-30. doi: 10.1016/j.bbr.2008.11.001. Epub 2008 Nov 11.
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.
1型糖尿病（T1D）伴有“糖尿病性脑病”，包括对应激的超敏反应、中风、痴呆和认知障碍风险增加。在之前的研究中，我们报告了几种大脑改变，包括在实验性T1D的自发模型和链脲佐菌素诱导模型中，海马增殖和存活率显著降低。本研究的目的是探讨链脲佐菌素处理的小鼠齿状回中与轻度神经退行性变相关的其他参数，以及与行为变化的潜在相关性。通过双皮质素（DCX）表达测量的神经发生状态显示，颗粒下区（SGZ）阳性细胞数量显著下降。然而，神经元迁移未受影响。我们发现，在齿状回门、SGZ和颗粒细胞层（GCL）中，细胞内脂褐素沉积显著增加，这是氧化应激增加和衰老的特征。糖尿病小鼠在学习和记忆测试中表现出显著受损，与对照小鼠相比，表现出逃避反应的潜伏期更长，主动回避反应的学习效率更低。在不对称高架十字迷宫的冲突环境中，探索性和非探索性活动均未受糖尿病状态的影响。总之，实验性糖尿病显示出齿状回有明显的变化迹象，这些变化与衰老过程中出现的变化相似。相应地，这些改变与学习和记忆测试中的表现下降一致。可能将神经和行为障碍联系起来的机制尚未完全明了。
