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Increased Expression and Altered Subcellular Distribution of Cathepsin B in Microglia Induces Cognitive Impairment through Oxidative Stress and Inflammatory response in Mice

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神经药理学报 2018年第2期 27-28页

作者： NI Jun-jun WU Zhou Veronika Stoka Christoph Peters QING Hong Vito Turk Hiroshi Nakanishi Department of Aging Science and Pharmacology Faculty of Dental ScienceKyushu University Department of Biochemistry and Molecular and Structural Biology J.Stefan Institute institute für molekulare medizin und zellforshung Albert-Ludwigs-Universit?t Freiburg Beijing Key Laboratory of Separation and Analysis in Biomedical and Pharmaceuticals Department of Biomedical EngineeringSchool of Life ScienceBeijing Institute of Technology

Objective:During normal aging,innate immunity progresses to a chronic state. However,how oxidative stress and chronic neuroinflammation arise during aging remain unclear. In this study,we intended to demonstrate the novel function of Cathepsin B（ CatB） in the age related oxidative stress and chronic neuroinflammation. Methods:（1）2 month-old and 20 month-old wild-type and CatB;mice were used for learning and memory tests by step through passive avoidance tests. The cumulative potentiation of the field excitatory postsynaptic potential（ f EPSP） slope and dendritic spine density were also examined.（2）Inflammation were examined by immunoblotting of interleukin-1β（ IL-1β）,tumor necrosis factor-α（ TNf-α） and inducible nitric oxide synthase（ i NOS）,and oxidative stress were examined by checking the level of 8-oxo-7,8-dihydro-2’-deoxyguanosine（ 8-oxo-d G） and 4-hydroxynonenal（ 4-HNE） in the hippocampal lysate of 2 month-old and 20 month-old wild-type and CatB;mice.（3）Intra-lateral ventricle transplantation of CatB over-expressed microglia in middleaged mice,learning and memory were examined by Y-maze and novel objective tests. results:（1）The retention latencies of both aged groups were significantly longer than those in the acquisition trial. The retention latency of four consecutive trials was significantly longer in aged CatB;mice than in aged wild-type mice. furthermore,the mean relative f EPSP slope measured at 30 min after stimulationwith 25,50 and 100 Hz in the aged CatB;mice was significantly larger than that in the aged wildtype mice. The mean dendritic spine density of CA1 neurons in the aged CatB;mice was significantly larger than that in the aged wild-type mice.（2）The mean levels of CatB,i NOS,IL-1β and TNf-α in the hippocampus were significantly higher in aged wild-type mice than in younger animals. furthermore,their mean levels in the hippocampus of aged CatB;mice were significantly lower than those in aged wild-type mice. The mean amounts of these oxidative ma

关键词： Increased Expression and Altered Subcellular Distribution of Cathepsin B in Microglia Induces Cognitive Impairment through Oxidative Stress and Inflammatory response in Mice HNE

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