TY - JOUR
T1 - Dissociation of functional status from accrual of CML and RAGE in the aged mouse brain
AU - Thangthaeng, Nopporn
AU - Sumien, Nathalie
AU - Forster, Michael J.
N1 - Funding Information:
This research was supported by National Institutes of Health–National Institute on Aging Grant P01 AG022550. The authors would like to thank Dr. Mark Smith for generously providing the CML antibody. The authors also thank Dr. Margaret Rutledge for assistance during paper preparation.
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
KW - Advanced glycation end products
KW - Aging
KW - Behavior
KW - Central nervous system
KW - Motor function
KW - N epsilon-(carboxymethyl)lysine
KW - Receptor for advanced glycation end products
UR - http://www.scopus.com/inward/record.url?scp=56349133537&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2008.08.045
DO - 10.1016/j.exger.2008.08.045
M3 - Article
C2 - 18783731
AN - SCOPUS:56349133537
SN - 0531-5565
VL - 43
SP - 1077
EP - 1085
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 12
ER -