Neuritin Attenuates Cognitive Function Impairments in Tg2576 Mouse Model of Alzheimer's Disease

PLoS One

Jun-Ho Lee¹  Seokyung Hahn²  Jin Won Hyun³  Hye-Sun Kim⁴  Ran-Sook Woo⁴  A Young Jeong⁴  Yoori Choi⁵  Hyoun Geun Kim⁵  Kihwan Lee⁵  Joung-Hun Kim⁶  Junghwa Ryu⁷ 

[1] Department of Anatomy and Neuroscience, School of Medicine, Eulji University, Daejeon, Republic of Korea;Department of Biochemistry, School of Medicine, Jeju National University, Jeju, Republic of Korea;Department of Emergency Medical Technology, Daejeon University, Daejeon, Republic of Korea;Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea;Department of Pharmacology and Biomedical Sciences, Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea;Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea;National Research Laboratory for Pain, Dental Research Institute and Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, Seoul, Republic of Korea

关键词: Neuronal dendrites;    Mouse models;    Dentate gyrus;    Neurons;    Alzheimer's disease;    Hippocampus;    Cognitive impairment;    Neurogenesis;   

DOI  :  10.1371/journal.pone.0104121

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s) and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD) patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.

【 授权许可】

CC BY