title: The hippocampus of Ames dwarf mice exhibits enhanced antioxidative defenses following kainic acid-induced oxidative stress.
abstract: BACKGROUND
  The vulnerability of the hippocampus to the effects of aging has been found to be associated with a decline in growth hormone/insulin like growth factor-1 (GH/IGF-1), and an increase in oxidative stress. We have evidence that long-living GH-deficient Ames dwarf mice have enhanced antioxidant protection in the periphery but the protection in the central nervous system is less clear.
  
  
  METHODS
  In the present study, we evaluated the antioxidative defense enzyme status in the hippocampus of Ames dwarf and wild type mice at 3, 12 and 24 months of age and examined the ability of each genotype to resist kainic acid-induced (KA) oxidative stress. An equiseizure concentration of KA was administered such that both genotypes responded with similar seizure scores and lipid peroxidation.
  
  
  RESULTS
  We found that GH-sufficient wild type mice showed an increase in oxidative stress as indicated by the reduced ratio of glutathione: glutathione disulfide following KA injection while this ratio was maintained in GH-deficient Ames dwarf mice. In addition, glutathione peroxidase activity (GPx) as well as GPx1 mRNA expression was enhanced in KA-injected Ames dwarf mice but decreased in wild type mice. There was no induction of Nrf-2 (an oxidative stress-induced transcription factor) gene expression in Ames dwarf mice following KA further suggesting maintenance of antioxidant defense in GH-deficiency under oxidative stress conditions.
  
  
  CONCLUSIONS
  Therefore, based on equiseizure administration of KA, Ames dwarf mice have an enhanced antioxidant defense capacity in the hippocampus similar to that observed in the periphery. This improved defense capability in the brain is likely due to increased GPx availability in Ames mice and may contribute to their enhanced longevity.
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA.
authors.forename: Sunita
authors.initials: S
authors.lastname: Sharma
authors.forename: Sharlene
authors.initials: S
authors.lastname: Rakoczy
authors.forename: Kristine
authors.initials: K
authors.lastname: Dahlheimer
authors.forename: Holly
authors.initials: H
authors.lastname: Brown-Borg
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
chemical_list: D018690:Excitatory Amino Acid Agonists; D051267:NF-E2-Related Factor 2; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D007608:Kainic Acid; D019803:Glutathione Disulfide
references.citation: J Neurosci Res. 2009 Feb 15;87(3):710-22
references.pmid: 18816793
references.citation: Brain Res. 1997 Jun 20;760(1-2):277-80
references.pmid: 9237547
references.citation: Gen Pharmacol. 1994 Jan;25(1):97-102
references.pmid: 8026720
references.citation: Free Radic Biol Med. 2001 Jun 1;30(11):1191-212
references.pmid: 11368918
references.citation: Free Radic Biol Med. 2008 Aug 15;45(4):443-52
references.pmid: 18501200
references.citation: Mech Ageing Dev. 2010 Jun;131(6):422-35
references.pmid: 20561541
references.citation: Endocrinology. 2010 Jul;151(7):3267-76
references.pmid: 20410204
references.citation: Neuropharmacology. 2004 Mar;46(4):580-9
references.pmid: 14975682
references.citation: Annu Rev Pharmacol Toxicol. 2007;47:89-116
references.pmid: 16968214
references.citation: Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E23-9
references.pmid: 15701676
references.citation: J Neurosci Res. 2007 Feb 15;85(3):497-503
references.pmid: 17171703
references.citation: Exp Neurol. 1983 Feb;79(2):422-33
references.pmid: 6822273
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915-22
references.pmid: 8367443
references.citation: Exp Brain Res. 2000 Jun;132(4):510-6
references.pmid: 10912831
references.citation: J Am Aging Assoc. 2001 Jul;24(3):85-96
references.pmid: 23604879
references.citation: J Neurochem. 1992 Nov;59(5):1609-23
references.pmid: 1402908
references.citation: J Neurotrauma. 2005 Jul;22(7):719-32
references.pmid: 16004576
references.citation: J Neurosci Methods. 2009 Apr 30;179(1):1-8
references.pmid: 19167427
references.citation: Exp Gerontol. 1996 May-Jun;31(3):365-72
references.pmid: 9415119
references.citation: Methods Enzymol. 1984;105:114-21
references.pmid: 6727659
references.citation: Carcinogenesis. 1987 Dec;8(12):1929-32
references.pmid: 3119248
references.citation: Neurobiol Aging. 1995 Jul-Aug;16(4):661-74
references.pmid: 8544918
references.citation: Neuroscience. 1980;5(6):991-1014
references.pmid: 7402461
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Behav Brain Res. 2002 Apr 1;131(1-2):211-20
references.pmid: 11844588
references.citation: Exp Gerontol. 2000 Mar;35(2):199-212
references.pmid: 10767579
references.citation: Arch Biochem Biophys. 1996 Sep 1;333(1):189-97
references.pmid: 8806770
references.citation: Free Radic Biol Med. 2000 Apr 15;28(8):1214-21
references.pmid: 10889451
references.citation: Neuroreport. 1991 Jun;2(6):345-7
references.pmid: 1832987
references.citation: Brain Res. 1997 Mar 14;751(1):37-46
references.pmid: 9098566
references.citation: Exp Gerontol. 2005 Jan-Feb;40(1-2):115-20
references.pmid: 15664737
references.citation: Free Radic Biol Med. 2000 Mar 1;28(5):779-85
references.pmid: 10754274
references.citation: Neurosci Lett. 2000 Mar 3;281(1):65-8
references.pmid: 10686417
references.citation: Brain Res Brain Res Rev. 2001 Dec;38(1-2):61-78
references.pmid: 11750927
references.citation: Free Radic Biol Med. 1996;20(6):821-30
references.pmid: 8728030
references.citation: Ann Neurol. 1992;32 Suppl:S10-5
references.pmid: 1510365
references.citation: Exp Neurol. 2006 Feb;197(2):309-17
references.pmid: 16364299
references.citation: Proc Natl Acad Sci U S A. 1996 May 14;93(10):4765-9
references.pmid: 8643477
references.citation: Mech Ageing Dev. 1994 Oct 20;76(2-3):215-24
references.pmid: 7885066
references.citation: Hippocampus. 2008;18(3):239-44
references.pmid: 18000817
references.citation: J Neurosci Methods. 1998 Jan 31;79(1):115-21
references.pmid: 9531467
references.citation: Glia. 2005 Aug 15;51(3):173-86
references.pmid: 15800930
references.citation: Exp Neurol. 2000 Nov;166(1):173-9
references.pmid: 11031093
references.citation: Neurochem Int. 2008 May;52(6):1134-47
references.pmid: 18226427
references.citation: Brain Res. 1996 Jul 15;727(1-2):133-44
references.pmid: 8842391
references.citation: Ageing Res Rev. 2007 May;6(1):28-45
references.pmid: 17360245
references.citation: Mech Ageing Dev. 2003 Dec;124(10-12):1013-24
references.pmid: 14659590
references.citation: Brain Res Brain Res Rev. 2001 Aug;36(1):60-90
references.pmid: 11516773
references.citation: J Neural Transm (Vienna). 2001;108(8-9):955-67
references.pmid: 11716148
references.citation: Endocrine. 1999 Aug;11(1):41-8
references.pmid: 10668640
references.citation: Neurobiol Aging. 2008 Nov;29(11):1680-9
references.pmid: 17524525
references.citation: Brain Res Mol Brain Res. 1997 Aug;48(1):145-8
references.pmid: 9379835
references.citation: J Gerontol A Biol Sci Med Sci. 2009 Aug;64(8):819-27
references.pmid: 19414510
references.citation: Cell Mol Neurobiol. 2005 Dec;25(8):1255-64
references.pmid: 16388336
references.citation: Brain Res Brain Res Rev. 1997 Dec;25(3):335-58
references.pmid: 9495562
references.citation: Brain Res. 2004 Oct 22;1024(1-2):59-76
references.pmid: 15451367
references.citation: Adv Enzymol Relat Areas Mol Biol. 1993;66:149-201
references.pmid: 8430514
references.citation: Mol Chem Neuropathol. 1992 Aug;17(1):51-63
references.pmid: 1326973
references.citation: Chem Res Toxicol. 1997 May;10(5):485-94
references.pmid: 9168245
references.citation: Exp Biol Med (Maywood). 2002 Feb;227(2):94-104
references.pmid: 11815672
references.citation: Cancer Res. 1982 May;42(5):1955-61
references.pmid: 7066906
references.citation: Free Radic Res. 1996 Aug;25(2):149-59
references.pmid: 8885333
references.citation: Biol Chem. 1997 Aug;378(8):793-802
references.pmid: 9377474
references.citation: Genome Res. 1996 Oct;6(10):986-94
references.pmid: 8908518
references.citation: Endocrine. 2003 Feb-Mar;20(1-2):149-54
references.pmid: 12668880
references.citation: Cell Signal. 2008 Apr;20(4):645-58
references.pmid: 18248956
references.citation: Respir Physiol. 2001 Nov 15;128(3):379-91
references.pmid: 11718765
references.citation: Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281-94
references.pmid: 4110397
references.citation: Ann Neurol. 2009 May;65(5):540-9
references.pmid: 19475669
references.citation: Neurology. 1998 Dec;51(6):1562-6
references.pmid: 9855502
references.citation: Exp Gerontol. 2001 Feb;36(2):209-20
references.pmid: 11226737
references.citation: Mol Cell Probes. 2002 Feb;16(1):25-30
references.pmid: 12005444
references.citation: Anal Biochem. 1980 Jul 15;106(1):207-12
references.pmid: 7416462
references.citation: J Neurosci Res. 2004 Nov 15;78(4):520-32
references.pmid: 15468179
references.citation: Brain Res. 2005 Feb 21;1035(1):24-31
references.pmid: 15713273
references.citation: Brain Res. 2008 May 13;1209:85-91
references.pmid: 18406401
references.citation: Free Radic Biol Med. 2009 Feb 15;46(4):443-53
references.pmid: 19028565
references.citation: Life Sci. 1993;53(10):857-64
references.pmid: 8394966
references.citation: Methods Enzymol. 1985;113:484-90
references.pmid: 3003504
references.citation: Mech Ageing Dev. 2006 Jan;127(1):57-63
references.pmid: 16243379
references.citation: Peptides. 1986 Jan-Feb;7(1):155-9
references.pmid: 3520509
references.citation: Neuroscience. 1995 Aug;67(3):551-9
references.pmid: 7675186
references.citation: Free Radic Biol Med. 1991;11(1):81-128
references.pmid: 1937131
references.citation: Neuroscience. 2007 Jul 29;147(4):1114-8
references.pmid: 17590518
references.citation: Mol Cell Neurosci. 2008 Sep;39(1):125-32
references.pmid: 18619545
references.citation: Exp Gerontol. 2009 Jan-Feb;44(1-2):10-9
references.pmid: 18675334
references.citation: J Biol Chem. 1974 Nov 25;249(22):7130-9
references.pmid: 4436300
references.citation: FASEB J. 2002 Jun;16(8):781-90
references.pmid: 12039859
references.citation: Neurochem Res. 2000 Oct;25(9-10):1439-51
references.pmid: 11059815
references.citation: Brain Res. 2000 Apr 17;862(1-2):83-9
references.pmid: 10799672
references.citation: Neurochem Res. 2004 Nov;29(11):2105-12
references.pmid: 15662844
references.citation: Cell Death Differ. 2002 Sep;9(9):1007-16
references.pmid: 12181751
references.citation: J Pineal Res. 2003 Mar;34(2):95-102
references.pmid: 12562500
references.citation: Free Radic Biol Med. 1995 Jun;18(6):993-1002
references.pmid: 7628735
references.citation: Exp Mol Pathol. 2008 Oct;85(2):135-40
references.pmid: 18586238
references.citation: J Neurochem. 2006 Sep;98(6):1852-65
references.pmid: 16945104