Brain aging and AD-like pathology in streptozotocin-induced diabetic rats.

Brain aging and AD-like pathology in streptozotocin-induced diabetic rats.
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链脲佐菌素诱导的糖尿病大鼠的脑老化和 AD 样病理学

DOI:
10.1155/2014/796840
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发表时间:
2014
影响因子:
4.3
通讯作者:
Jing YH
Jing YH
中科院分区:
医学3区
文献类型:
--
作者:
Wang JQ;Yin J;Song YF;Zhang L;Ren YX;Wang DG;Gao LP;Jing YH

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Objective.许多流行病学研究已经将糖尿病(DM)与发展阿尔茨海默病(AD)的风险增加联系起来。然而,糖尿病脑病是否表现出AD样病理仍不清楚。研究设计和方法。采用体视学方法对链脲佐菌素(STZ)诱导的大鼠连续冠状脑切片测量前脑和海马体积。使用Fluoro-Jade C(FJC)评价额叶皮质、下丘脑和海马的神经变性。采用免疫组化和ELISA法检测Aβ在额叶皮质和海马的聚集。采用高尔基体染色法检测额叶皮质和海马树突棘密度,Western blot法检测突触素水平。采用Morris水迷宫和抑制性回避盒评价大鼠的认知能力。结果大鼠在注射STZ后表现为胰岛素缺乏伴多饮、多食、多尿和体重减轻。与年龄匹配的对照组大鼠相比,糖尿病大鼠离散脑区FJC阳性细胞的数量显着增加。与对照组相比,糖尿病大鼠海马萎缩,Aβ聚集,突触丢失。与同龄对照组相比,糖尿病大鼠的学习记忆能力下降。结论.我们的研究结果表明,代谢异常导致脑老化的特点是AD样病理。
Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.
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