Immune response gene expression increases in the aging murine hippocampus.
Using GeneChips, basal and lipopolysaccharide (LPS)-induced gene expression was examined in the hippocampus of 3-, 12-, 18- and 24-month-old male C57BL/6 mice to identify genes whose altered expression could influence hippocampal function in advanced age. Gene elements that changed with age were selected with a t-statistic and specific expression patterns were confirmed with real-time quantitative PCR. Basal expression of 128 gene elements clearly changed with age in the hippocampus. Fourteen gene elements showed increased expression with age and these increases were validated after LPS stimulation. Major histocompatibility complex (MHC) TL region and thymic shared antigen (TSA-1) gene expression increased, suggesting T cell activation in the hippocampus with age. Cytokine (interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha) and chemokine (macrophage chemotactic protein-1) expression increased sharply in 24-month-old mice. These findings are in contrast to a decrease in the peripheral immune response, documented by decreased T cell proliferation and decreased ratios of naive to memory T cells. Age-related increases in inflammatory potential in the brain may contribute to neurodegenerative diseases of the aged.
Terao
Akira
A
SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
Apte-Deshpande
Anjali
A
Dousman
Linda
L
Morairty
Stephen
S
Eynon
Barrett P
BP
Kilduff
Thomas S
TS
Freund
Yvonne R
YR
D000375:Aging / Q000276:immunology*; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015922:Complement C1q / Q000235:genetics; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006624:Hippocampus / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics
D000953:Antigens, Protozoan; D001057:Apolipoproteins E; D008070:Lipopolysaccharides; D014643:Variant Surface Glycoproteins, Trypanosoma; C070842:trypomastigote specific surface antigen; D015922:Complement C1q