title: Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes.
abstract: Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Aβ overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes.
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ao-Ji
authors.initials: AJ
authors.lastname: Xie
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: En-Jie
authors.initials: EJ
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: He-Zhou
authors.initials: HZ
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Youming
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. zhulq1979@gmail.com.|The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China. zhulq1979@gmail.com.|Sino-Canada Collaborative Platform on Molecular Biology of Neurological Disease, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. zhulq1979@gmail.com.|Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, People's Republic of China. zhulq1979@gmail.com.
authors.forename: Ling-Qiang
authors.initials: LQ
authors.lastname: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009830:Olfactory Bulb / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000096:biosynthesis
chemical_list: D016229:Amyloid beta-Peptides; C518240:Cnga2 protein, mouse; D054815:Cyclic Nucleotide-Gated Cation Channels; D016875:tau Proteins
keywords: Alzheimer’s disease; Aβ; Cnga2; Tau