title: Dissociation of functional status from accrual of CML and RAGE in the aged mouse brain.
abstract: The objectives of this study were: (i) to identify regions of the aged mouse brain in which advanced glycation end-products (AGEs) were increased, and (ii) assess the functional significance of AGEs by determining the extent to which they could predict age-related brain dysfunction. Densitometric analyses of immunoblots for N epsilon-(carboxymethyl)lysine (CML), a predominant AGE, and receptor for AGE (RAGE), were performed in different brain regions of mice aged 8 or 25 months. The 25-month-old mice were tested for ability to perform on tests of cognitive and psychomotor function prior to assessment of CML or RAGE, to determine if immunostaining results could predict functional impairment among the older mice. The amounts of CML increased with age in cortex, hippocampus, striatum, and midbrain, but were unchanged in the brainstem and cerebellum. Increases in RAGE were evident in all brain regions but the hippocampus, and were not linked to increased amounts of CML. Different statistical approaches each failed to reveal any strong association between the degree of age-related functional impairment among individual mice and amounts of CML or RAGE in any particular region of the brain. The findings from this study suggest that accrual of CML and expression of RAGE in different brain regions are time-related phenomena that do not account for individual differences in brain aging or cognitive decline.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Nopporn
authors.initials: N
authors.lastname: Thangthaeng
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sumien
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Forster
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D003720:Densitometry; D004213:Dissociative Disorders / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011597:Psychomotor Performance / Q000502:physiology
chemical_list: D017127:Glycation End Products, Advanced
references.citation: Biochemistry. 1989 Nov 28;28(24):9464-8
references.pmid: 2514802
references.citation: J Biol Chem. 2005 Jun 3;280(22):21522-30
references.pmid: 15799962
references.citation: Nat Rev Neurosci. 2006 Jan;7(1):30-40
references.pmid: 16371948
references.citation: Free Radic Biol Med. 2005 Mar 15;38(6):729-36
references.pmid: 15721983
references.citation: Glycobiology. 2005 Jul;15(7):16R-28R
references.pmid: 15764591
references.citation: Proc Natl Acad Sci U S A. 1996 May 14;93(10):4765-9
references.pmid: 8643477
references.citation: J Biol Chem. 1998 Sep 25;273(39):25272-8
references.pmid: 9737992
references.citation: Biochem Biophys Res Commun. 1998 Sep 18;250(2):385-9
references.pmid: 9753639
references.citation: Exp Aging Res. 1981 Winter;7(4):427-51
references.pmid: 7333338
references.citation: Methods Find Exp Clin Pharmacol. 2003 Jul-Aug;25(6):447-52
references.pmid: 12949630
references.citation: Biochemistry. 1990 Dec 11;29(49):10964-70
references.pmid: 2125497
references.citation: Neurobiol Aging. 1999 Mar-Apr;20(2):167-76
references.pmid: 10537026
references.citation: Neurobiol Aging. 1999 Nov-Dec;20(6):617-27
references.pmid: 10674427
references.citation: Biochem J. 1997 Jun 1;324 ( Pt 2):565-70
references.pmid: 9182719
references.citation: J Biol Chem. 2000 Dec 22;275(51):40096-105
references.pmid: 11007787
references.citation: Brain Res. 1998 Apr 27;791(1-2):11-7
references.pmid: 9593803
references.citation: Age (Dordr). 2006 Sep;28(3):265-82
references.pmid: 22253494
references.citation: Neurobiol Aging. 1996 May-Jun;17(3):491-5
references.pmid: 8725914
references.citation: Restor Neurol Neurosci. 1998 Jun;12(2-3):167-73
references.pmid: 12671312
references.citation: Brain Res Mol Brain Res. 1999 Feb 19;65(1):124-8
references.pmid: 10036314
references.citation: Behav Pharmacol. 1992 Aug;3(4):337-349
references.pmid: 11224136
references.citation: Free Radic Biol Med. 2004 Jun 1;36(11):1424-33
references.pmid: 15135179
references.citation: J Neurophysiol. 2006 Mar;95(3):1509-17
references.pmid: 16338994
references.citation: Neurosci Lett. 1996 Apr 12;208(1):53-6
references.pmid: 8731173
references.citation: Arch Biochem Biophys. 1996 Sep 1;333(1):189-97
references.pmid: 8806770
references.citation: Brain Res Brain Res Rev. 2003 Mar;41(2-3):306-23
references.pmid: 12663085
references.citation: Biochemistry. 1991 Feb 5;30(5):1205-10
references.pmid: 1899338
references.citation: Ann N Y Acad Sci. 2001 Apr;928:48-53
references.pmid: 11795527
references.citation: Neurobiol Aging. 1995 Jan-Feb;16(1):69-76
references.pmid: 7723938
references.citation: Biochem Biophys Res Commun. 1997 Jul 18;236(2):327-32
references.pmid: 9240434
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2000 Oct;63(4):177-86
references.pmid: 11049692
references.citation: Biochemistry. 1995 Aug 29;34(34):10872-8
references.pmid: 7662668
references.citation: Diabetes Metab Res Rev. 2001 Nov-Dec;17(6):436-43
references.pmid: 11757079
references.citation: Free Radic Biol Med. 2001 Jul 15;31(2):175-80
references.pmid: 11440829
references.citation: Am J Pathol. 1998 Oct;153(4):1149-55
references.pmid: 9777946
references.citation: FASEB J. 2000 Jan;14(1):145-56
references.pmid: 10627289
references.citation: J Biol Chem. 2000 Dec 15;275(50):39027-31
references.pmid: 10976109
references.citation: Behav Brain Res. 2002 Feb 1;129(1-2):107-12
references.pmid: 11809501
references.citation: Neuroscience. 2001;107(3):415-31
references.pmid: 11718997
references.citation: Annu Rev Psychol. 1997;48:339-70
references.pmid: 9046563
references.citation: J Clin Invest. 1993 Jun;91(6):2463-9
references.pmid: 8514858
references.citation: Age (Dordr). 2006 Sep;28(3):235-53
references.pmid: 22253492
references.citation: Acta Neuropathol. 2002 Aug;104(2):113-22
references.pmid: 12111353
references.citation: Brain Res. 2007 Jan 5;1127(1):10-8
references.pmid: 17113050
references.citation: Biochem J. 1997 Dec 1;328 ( Pt 2):599-605
references.pmid: 9371721
references.citation: Biochim Biophys Acta. 2000 Dec 20;1498(2-3):99-111
references.pmid: 11108954
references.citation: Ageing Res Rev. 2004 Nov;3(4):431-43
references.pmid: 15541710