Interleukin 17A deficiency alleviates neuroinflammation and cognitive impairment in an experimental model of diabetic encephalopathy  

作　　者：Xiao-Xia Fang Fen-Fen Xu Zhan Liu Bei-Bei Cao Yi-Hua Qiu Yu-Ping Peng 

机构地区：[1]Department of Physiology,School of Medicine,and Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2022年第12期2771-2777,共7页中国神经再生研究（英文版）

基　　金：supported by the Natural Science Foundation of Jiangsu Province of China, No.BK20180948(to ZL);Nantong Applied Research Program of China, No.MS12019011(to XXF);Science and Technology Project of Nantong University of China, No.TDYXY2019007(to XXF)

摘　　要：Interleukin 17A(IL-17A)was previously shown to be a key pro-inflammatory factor in diabetes mellitus and associated complications.However,the role of IL-17A in diabetic encephalopathy remains poorly understood.In this study,we established a mouse model of diabetic encephalopathy that was deficient in IL-17A by crossing Il17a-/-mice with spontaneously diabetic Ins2^(Akita)(Akita)mice.Blood glucose levels and body weights were monitored from 2-32 weeks of age.When mice were 32 weeks of age,behavioral tests were performed,including a novel object recognition test for assessing short-term memory and learning and a Morris water maze test for evaluating hippocampus-dependent spatial learning and memory.IL-17A levels in the serum,cerebrospinal fluid,and hippocampus were detected with enzyme-linked immunosorbent assays and real-time quantitative polymerase chain reaction.Moreover,proteins related to cognitive dysfunction(amyloid precursor protein,β-amyloid cleavage enzyme 1,p-tau,and tau),apoptosis(caspase-3 and-9),inflammation(inducible nitric oxide synthase and cyclooxygenase 2),and occludin were detected by western blot assays.Pro-inflammatory cytokines including tumor necrosis factor-α,interleukin-1β,and interferon-γin serum and hippocampal tissues were measured by enzyme-linked immunosorbent assays.Microglial activation and hippocampal neuronal apoptosis were detected by immunofluorescent staining.Compared with that in wild-type mice,mice with diabetic encephalopathy had higher IL-17A levels in the serum,cerebrospinal fluid,and hippocampus;downregulation of occludin expression;lower cognitive ability;greater loss of hippocampal neurons;increased microglial activation;and higher expression of inflammatory factors in the serum and hippocampus.IL-17A knockout attenuated the abovementioned changes in mice with diabetic encephalopathy.These findings suggest that IL-17A participates in the pathological process of diabetic encephalopathy.Furthermore,IL-17A deficiency reduces diabetic encephalopathy-mediated neuroinflam

关 键 词：Akita mice apoptosis cognitive impairment diabetic encephalopathy HIPPOCAMPUS interleukin 17A MICE MICROGLIA NEUROINFLAMMATION neuron targeted treatment 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学] R-332[医药卫生—临床医学]