title: Neuritin attenuates cognitive function impairments in tg2576 mouse model of Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yoori
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Neuroscience Research Institute, College of Medicine, Seoul National University, 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.
authors.forename: Kihwan
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Junghwa
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Hyoun Geun
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: A Young
authors.initials: AY
authors.lastname: Jeong
authors.affiliation: Department of Anatomy and Neuroscience, School of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: Ran-Sook
authors.initials: RS
authors.lastname: Woo
authors.affiliation: Department of Emergency Medical Technology, Daejeon University, Daejeon, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Medicine, Jeju National University, Jeju, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Seokyung
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Department of Life Science, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Biomedical Sciences, Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea; Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, Republic of Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018782:Maze Learning; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism* / Q000502:physiology; D017207:Rats, Sprague-Dawley
chemical_list: D058851:GPI-Linked Proteins; C484539:NRN1 protein, human; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C484377:Nrn1 protein, mouse
references.citation: Nat Neurosci. 2008 Aug;11(8):901-7
references.pmid: 18622400
references.citation: Nat Neurosci. 2005 Mar;8(3):322-31
references.pmid: 15711540
references.citation: Nature. 1996 Jul 25;382(6589):363-6
references.pmid: 8684467
references.citation: Neuroscience. 2004;126(2):305-12
references.pmid: 15207348
references.citation: Neuron. 2005 Feb 17;45(4):505-12
references.pmid: 15721237
references.citation: Diabetes. 2008 Jan;57(1):181-9
references.pmid: 17909094
references.citation: Science. 1996 Oct 4;274(5284):99-102
references.pmid: 8810256
references.citation: Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2048-53
references.pmid: 8700883
references.citation: Science. 1993 Jun 18;260(5115):1819-21
references.pmid: 8511592
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2648-53
references.pmid: 9122250
references.citation: J Alzheimers Dis. 2006;9(3 Suppl):91-9
references.pmid: 16914848
references.citation: Nature. 2006 Aug 17;442(7104):814-7
references.pmid: 16862120
references.citation: J Alzheimers Dis. 2014;38(1):11-38
references.pmid: 23948932
references.citation: Science. 2002 Oct 25;298(5594):789-91
references.pmid: 12399581
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):428-437
references.pmid: 19569075
references.citation: Neuroscience. 2004;127(3):601-9
references.pmid: 15283960
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3399-404
references.pmid: 16492766
references.citation: Neurology. 2001 Jan 9;56(1):127-9
references.pmid: 11148253
references.citation: J Mol Neurosci. 2010 Jan;40(1-2):221-9
references.pmid: 19690986
references.citation: Neurology. 2007 May 1;68(18):1501-8
references.pmid: 17470753
references.citation: Nat Rev Neurosci. 2001 Dec;2(12):880-8
references.pmid: 11733795
references.citation: J Comp Neurol. 2001 Jul 9;435(4):464-73
references.pmid: 11406826
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11378-83
references.pmid: 22733766
references.citation: Nat Neurosci. 2007 Jun;10(6):727-34
references.pmid: 17486101
references.citation: Acta Neuropathol. 2003 Mar;105(3):225-32
references.pmid: 12557008
references.citation: J Neurotrauma. 2007 Apr;24(4):722-31
references.pmid: 17439354
references.citation: Front Behav Neurosci. 2014 Apr 01;8:106
references.pmid: 24744707
references.citation: Nature. 1993 Jun 24;363(6431):718-22
references.pmid: 8515813
references.citation: Mol Cell Neurosci. 2003 Nov;24(3):538-54
references.pmid: 14664806
references.citation: J Comp Neurol. 2008 Apr 10;507(5):1831-45
references.pmid: 18265009
references.citation: Science. 1998 Sep 18;281(5384):1863-6
references.pmid: 9743502
references.citation: Physiol Rev. 2005 Apr;85(2):523-69
references.pmid: 15788705
references.citation: Nature. 2002 Feb 28;415(6875):1030-4
references.pmid: 11875571
references.citation: Neurobiol Dis. 2008 Jan;29(1):71-80
references.pmid: 17916429
references.citation: J Neurosci. 1999 Sep 15;19(18):7999-8008
references.pmid: 10479700
references.citation: Neuron. 2001 Dec 6;32(5):911-26
references.pmid: 11738035
references.citation: Neurology. 1994 Nov;44(11):2081-8
references.pmid: 7969963
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13363-7
references.pmid: 15340159
references.citation: Nat Neurosci. 2000 Oct;3(10):1004-11
references.pmid: 11017173
references.citation: J Neurochem. 2005 Jan;92(1):10-20
references.pmid: 15606892
references.citation: J Comp Neurol. 2006 Mar 1;495(1):70-83
references.pmid: 16432899
references.citation: Acta Neuropathol. 2009 Jul;118(1):167-79
references.pmid: 19390859
references.citation: Acta Neuropathol. 2008 Oct;116(4):419-24
references.pmid: 18483741
references.citation: Nature. 2004 Aug 5;430(7000):631-9
references.pmid: 15295589
references.citation: J Neurosci. 2010 Feb 17;30(7):2636-49
references.pmid: 20164348