title: Repeated administration of PEP-1-Cu,Zn-superoxide dismutase and PEP-1-peroxiredoxin-2 to senescent mice induced by D-galactose improves the hippocampal functions.
abstract: Oxidative stress initiates age-related reduction in hippocampal neurogenesis and the use of antioxidants has been proposed as an effective strategy to prevent or attenuate the reduction of neurogenesis in the hippocampus. In the present study, we investigated the effects of Cu,Zn-superoxide dismutase (SOD1) and/or peroxiredoxin-2 (PRX2) on cell proliferation and neuroblast differentiation in the dentate gyrus in a model of D-galactose-induced aging model. For this study, we constructed an expression vector, PEP-1, fused PEP-1 with SOD1 or PRX2, and generated PEP-1-SOD1 and PEP-1-PRX2 fusion protein. The aging model was induced by subcutaneous injection of D-galactose (100 mg/kg) to 6-week-old male mice for 10 weeks. PEP-1, PEP-1-SOD1 and/or PEP-1-PRX2 fusion protein was intraperitoneally administered to these mice at 13-week-old once a day for 3 weeks and sacrificed at 30 min after the last administrations. The administration of PEP-1-SOD1 and/or PEP-1-PRX2 significantly improved D-galactose-induced deficits on the escape latency, swimming speeds, platform crossings, spatial preference for the target quadrant in Morris water maze test. In addition, the administration of PEP-1-SOD1 and/or PEP-1-PRX2 ameliorated D-galactose-induced reductions of cell proliferation and neuroblast differentiation in the dentate gyrus and significantly reduced D-galactose-induced lipid peroxidation in the hippocampus. These effects were more prominent in the PEP-1-SOD1-treated group with PEP-1-PRX2. These results suggest that a SOD1 and/or PRX2 supplement to aged mice could improve the memory deficits, cell proliferation and neuroblast differentiation in the dentate gyrus of D-galactose induced aged mice by reducing lipid peroxidation.
authors.affiliation: Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Hoon Jae
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Woosuk
authors.initials: W
authors.lastname: Kim
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Nam
authors.forename: Jong Hwi
authors.initials: JH
authors.lastname: Kim
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003543:Cysteamine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005690:Galactose / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D055495:Neurogenesis; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage; D054464:Peroxiredoxins / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D000072105:Superoxide Dismutase-1
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003543:Cysteamine; D054464:Peroxiredoxins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005690:Galactose
references.citation: J Comp Neurol. 1965 Jun;124(3):319-35
references.pmid: 5861717
references.citation: J Pineal Res. 2009 Jan;46(1):71-8
references.pmid: 18798786
references.citation: Antioxid Redox Signal. 2007 Feb;9(2):181-9
references.pmid: 17115939
references.citation: Neuroscience. 1991;44(2):353-9
references.pmid: 1658680
references.citation: Neurobiol Aging. 2011 Jun;32(6):1054-68
references.pmid: 19577336
references.citation: Mech Ageing Dev. 1999 May 17;108(3):239-51
references.pmid: 10405984
references.citation: J Neurosci. 1999 Dec 15;19(24):10977-84
references.pmid: 10594078
references.citation: Toxicology. 2009 Jan 8;255(1-2):107-14
references.pmid: 19014992
references.citation: Nature. 2004 May 13;429(6988):184-7
references.pmid: 15107864
references.citation: J Biol Chem. 1969 Nov 25;244(22):6049-55
references.pmid: 5389100
references.citation: Biochim Biophys Acta. 2014 Jul;1840(7):2321-30
references.pmid: 24631653
references.citation: J Neurosci Res. 2002 Oct 1;70(1):1-7
references.pmid: 12237859
references.citation: Methods Enzymol. 1990;186:1-85
references.pmid: 2172697
references.citation: Eur J Neurosci. 2011 Sep;34(6):930-50
references.pmid: 21929626
references.citation: Anal Biochem. 1971 Nov;44(1):276-87
references.pmid: 4943714
references.citation: J Alzheimers Dis. 2007 Aug;12(1):61-72
references.pmid: 17851195
references.citation: Neurochem Res. 2006 Jun;31(6):741-50
references.pmid: 16794860
references.citation: Free Radic Biol Med. 2009 Nov 15;47(10):1459-67
references.pmid: 19703553
references.citation: Eur J Neurosci. 1998 Feb;10(2):538-44
references.pmid: 9749716
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10032-7
references.pmid: 10944195
references.citation: J Neurochem. 1992 Nov;59(5):1609-23
references.pmid: 1402908
references.citation: Neurobiol Aging. 2003 Mar-Apr;24(2):267-72
references.pmid: 12498960
references.citation: Neurochem Int. 2010 May-Jun;56(6-7):740-6
references.pmid: 19958807
references.citation: Neurochem Res. 2012 Feb;37(2):261-7
references.pmid: 21927927
references.citation: Metab Brain Dis. 2010 Dec;25(4):419-24
references.pmid: 21082337
references.citation: Ann Clin Lab Sci. 1998 Nov-Dec;28(6):331-46
references.pmid: 9846200
references.citation: J Neurosci. 2009 Oct 14;29(41):12795-801
references.pmid: 19828791
references.citation: Neurobiol Aging. 2011 Oct;32(10):1906-14
references.pmid: 20006411
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Aging Cell. 2008 Aug;7(4):569-89
references.pmid: 18221417
references.citation: Eur J Neurosci. 2011 Sep;34(6):978-87
references.pmid: 21929629
references.citation: Antioxid Redox Signal. 2007 Feb;9(2):201-10
references.pmid: 17115934
references.citation: Brain Res. 2012 Apr 17;1449:83-93
references.pmid: 22418058
references.citation: J Comp Neurol. 2003 Dec 1;467(1):1-10
references.pmid: 14574675
references.citation: Proc Natl Acad Sci U S A. 1996 May 14;93(10):4765-9
references.pmid: 8643477
references.citation: Free Radic Biol Med. 2004 Nov 15;37(10):1656-69
references.pmid: 15477017
references.citation: Cell. 2009 Nov 13;139(4):814-27
references.pmid: 19914173
references.citation: J Comp Neurol. 2011 Feb 15;519(3):451-66
references.pmid: 21192078
references.citation: J Neurosci. 1997 Nov 15;17(22):8695-701
references.pmid: 9348338
references.citation: Am J Physiol Regul Integr Comp Physiol. 2002 Apr;282(4):R985-92
references.pmid: 11893601
references.citation: J Neurosci Res. 2007 Nov 1;85(14):3089-97
references.pmid: 17663478
references.citation: Nat Neurosci. 2007 Jun;10(6):727-34
references.pmid: 17486101
references.citation: Eur J Neurosci. 2000 Jan;12(1):345-52
references.pmid: 10651889
references.citation: Free Radic Biol Med. 2005 Aug 1;39(3):392-402
references.pmid: 15993338
references.citation: Prog Neurobiol. 2003 Feb;69(3):143-79
references.pmid: 12758108
references.citation: Curr Opin Cell Biol. 2005 Apr;17(2):183-9
references.pmid: 15780595
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18742-7
references.pmid: 18003920
references.citation: J Neurosci. 2003 Nov 12;23(32):10359-67
references.pmid: 14614095
references.citation: J Neurochem. 2003 Aug;86(4):860-8
references.pmid: 12887684
references.citation: Curr Opin Clin Nutr Metab Care. 2002 Nov;5(6):645-51
references.pmid: 12394639
references.citation: Nat Med. 1998 Nov;4(11):1313-7
references.pmid: 9809557
references.citation: Nature. 2002 Feb 28;415(6875):1030-4
references.pmid: 11875571
references.citation: J Neurosci Res. 2002 Nov 1;70(3):298-308
references.pmid: 12391589
references.citation: J Biol Chem. 1997 Aug 15;272(33):20313-6
references.pmid: 9252331
references.citation: Trends Immunol. 2007 Jan;28(1):5-11
references.pmid: 17140851
references.citation: J Bacteriol. 2001 Dec;183(24):7173-81
references.pmid: 11717276
references.citation: Food Chem Toxicol. 2009 Mar;47(3):625-32
references.pmid: 19146912
references.citation: Neuroscience. 2001;107(3):415-31
references.pmid: 11718997
references.citation: J Biol Chem. 2008 Feb 29;283(9):5389-401
references.pmid: 18174165
references.citation: Eur J Neurosci. 2005 Jan;21(1):1-14
references.pmid: 15654838
references.citation: Cell. 2008 Feb 22;132(4):645-60
references.pmid: 18295581
references.citation: Nat Neurosci. 2007 Mar;10(3):355-62
references.pmid: 17277773
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):6064-9
references.pmid: 20231460
references.citation: Ann N Y Acad Sci. 2006 Dec;1091:102-9
references.pmid: 17341607
references.citation: J Mol Neurosci. 2008 Nov;36(1-3):61-72
references.pmid: 18491044
references.citation: Ageing Res Rev. 2004 Nov;3(4):431-43
references.pmid: 15541710
references.citation: J Neurosci Res. 2006 Aug 15;84(3):647-54
references.pmid: 16710848
references.citation: J Pineal Res. 2012 Jan;52(1):21-8
references.pmid: 21718363
references.citation: Prog Neurobiol. 2008 Apr;84(4):317-28
references.pmid: 18308460