Cognitive deficits and Alzheimer-like neuropathological impairments during adolescence in a rat model of type 2 diabetes mellitus

作     者：Li Jin Yi-Pei Li Qiong Feng Li Ren Fang Wang Guo-Jia Bo Li Wang 

作者机构：Department of PathophysiologyHenan Medical College Henan Key Laboratory of Degenerative Brain DiseaseHenan Medical College Department of PathophysiologySchool of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and Technology Department of PathologyWuhan Children's Hospital 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2018年第13卷第11期

页      面：1995-2004页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100203[医学-老年医学] 10[医学] 

基　　金：principally supported by the Initial Funding of PhD Research from Henan Medical College of China,No.1001/0106 in parts by the Science and Technology Project of Henan Province of China,No.172102310105 

主　　题：nerve regeneration type 2 diabetes mellitus Alzheimer's disease monosodium glutamate neonatal period cognitive deficits hyperglycemia hyperinsulinemia insulin resistance neural regeneration 

摘      要：Numerous studies have shown that many patients who suffer from type 2 diabetes mellitus exhibit cognitive dysfunction and neuronal synaptic impairments. Therefore, growing evidence suggests that type 2 diabetes mellitus has a close relationship with occurrence and progression of neurodegeneration and neural impairment in Alzheimer＇s disease. However, the relationship between metabolic disorders caused by type 2 diabetes mellitus and neurodegeneration and neural impairments in Alzheimer＇s disease is still not fully determined. Thus, in this study, we replicated a type 2 diabetic animal model by subcutaneous injection of newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period. At 3 months old, the Barnes maze assay was performed to evaluate spatial memory function. Microelectrodes were used to measure electrophysiological function in the hippocampal CA1 region. Western blot assay was used to determine expression levels of glutamate ionotropic receptor NMDA type subunit 2 A（GluN2A） and GluN2B in the hippocampus. Enzyme-linked immunosorbent assay was used to determine levels of interleukin-1β, tumor necrosis factor α, and interleukin-6 in the hippocampus and cerebral cortex, as well as hippocampal amyloid beta（Aβ）1-40 and Aβ_（1-42） levels. Our results showed that in the rat model of type 2 diabetes mellitus caused by monosodium glutamate exposure during the neonatal period, latency was prolonged and the number of errors increased in the Barnes maze. Further, latency was increased and time in the escape platform quadrant shortened. Number of times crossing the platform was also reduced in the Morris water maze. After high frequency stimulation of the hippocampus, synaptic transmission was inhibited, expression of GluN2A and GluN2B were decreased in the hippocampus, expression of interleukin 1β, interleukin 6, and tumor necrosis factor α was increased in the hippocampus and cortex, and levels of Aβ_（1-40） and Aβ_（1-42） were increased in the hippoc