Increased chemokine gene expression during aging in the murine brain.
Normal aging results in changes in the brain that contribute to the decline of various functions, including learning and memory. Mechanisms causing this decline have not been clearly established. Activation of microglia is associated with the normal aging process in rodents and primates. Microglial activation is regulated by chemokine gene expression, and activated microglia produce substances that can be detrimental to surrounding cells. In this study we determined whether changes in chemokine expression occur during normal aging in the mouse brain. RNA samples taken from the cortex, midbrain, hippocampus, and cerebellum of 4-, 10-, 21- and 30-month-old C57BL6/DBA2 mice were analyzed for changes in gene expression. RNase protection assays were used to examine a panel of chemokines. Increased expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES occurred in all four regions of the brains in the oldest mice. These increases were first detectable at 21 months of age. Increases in MIP-1alpha, MIP-1beta, and RANTES protein levels were also detected in the brains of old mice, as measured by ELISA. Increased microglial activation in the brains of 30-month-old mice, as detected by immunohistochemistry using F4/80 antibodies, correlated with increases in chemokine expression. The observed increases in chemokine gene expression that occur in conjunction with increased microglial activation suggest that chemokines may contribute to the decreased brain function that occurs during normal aging.
Felzien
L K
LK
Department of Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. lisa.felzien@rockhurst.edu
McDonald
J T
JT
Gleason
S M
SM
Berman
N E
NE
Klein
R M
RM
D000375:Aging / Q000276:immunology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000276:immunology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017628:Microglia / Q000276:immunology; D015213:Neuroimmunomodulation / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger