Involvement of pro-inflammatory cytokines and microglia in an age-associated neurodegeneration model, the SAMP10 mouse.
The SAMP10 mouse strain is a model of brain aging in which senescence is characterized by cerebral atrophy and neurodegeneration phenotypes. To investigate the role of neuroinflammation in the age-associated neurodegeneration of SAMP10 mice, we assessed the expression of several cytokines and chemokines in the atrophy-prone brain region of SAMP10, and control, SAMR1 mice, which show a normal aging process. We also studied morphological changes in microglia with advancing age in atrophied regions. The expression of IL-1beta and IFN-gamma mRNA was about 2-fold greater in SAMP10 mice as compared to SAMR1 mice throughout their life span. The expression of IL-6 mRNA was 2.0-fold greater in SAMP10 mice as compared to SAMR1 mice at 14 months of age, although there was no difference at 3 months of age. Fourteen-month-old mice had a 2.1-fold greater expression of TNF-alpha mRNA than 3-month-old mice in both strains. The expression of MCP-1 mRNA was greater in SAMP10 mice than SAMR1 mice, and tended to increase with advancing age. Activated microglia were rarely observed in both strains at 3 months of age. At 14 months of age, however, SAMP10 mice had a 5.6-fold greater number of activated microglia than SAMR1 mice. The aforementioned results suggest the presence of a higher pro-inflammatory status in the atrophy-prone brain region of SAMP10 mice as compared to SAMR1 mice. Neuroinflammation is a possible mechanism of age-associated neurodegeneration in SAMP10 mice.
Kumagai
Naoko
N
Laboratory of Immunobiology, Department of Life Science, Niigata University Graduate School of Science and Technology, 950-2181, Niigata City, Niigata, Japan.
Chiba
Yoichi
Y
Hosono
Masamichi
M
Fujii
Masato
M
Kawamura
Noriko
N
Keino
Hiromi
H
Yoshikawa
Keisuke
K
Ishii
Sanae
S
Saitoh
Yuko
Y
Satoh
Mamoru
M
Shimada
Atsuyoshi
A
Hosokawa
Masanori
M
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger