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Overexpression of UCP2 does not diminish expression of neuroinflammatory mediators in the aged mouse hypothalamus
Author(s) -
Walker Keya M.,
Hamilton Jock S.,
Chau Sat M.,
Warden Craig H.,
McDonald Roger B.,
Horwitz Barbara A.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.80
Subject(s) - neuroinflammation , neuroprotection , endocrinology , medicine , genetically modified mouse , hypothalamus , knockout mouse , biology , tumor necrosis factor alpha , transgene , inflammation , receptor , gene , biochemistry
Neuroinflammation associated with advanced aging is attenuated by caloric restriction (CR). Mitochondrial uncoupling protein (UCP)‐2 is neuroprotective in certain models of brain injury and trauma. We hypothesized that increased UCP2 would mimic CR in attenuating age‐related neuroinflammation, while lack of UCP2 would enhance such neuroinflammation. We used real‐time quantitative PCR to measure mRNA for UCP2, IL‐1β, TNF‐α, IL‐6, and iNOS in mouse hypothalami isolated from 8, 19, and 26‐mo old female transgenic mice overexpressing UCP2, their non‐overexpressing littermates, UCP2‐knockouts (2KO), C57BL6/J wild‐type controls, and C57BL6/J wild‐type CR mice (n=9‐10/group). Although expression of IL‐1β and TNF‐α increased between 8 and 26‐months of age in all groups (p<0.05), the magnitudes of these increases were lower in CR than in any other group. In contrast, the age related decline in IL‐6 expression was unaffected by CR or UCP2 overexpression, while 2KO mice exhibited no age‐related decline. iNOS expression was unaffected by age or animal group, and UCP2 expression was unaffected by age or CR. Thus, UCP2 overexpression did not mimic CR nor did the absence of UCP2 in 2KO mice exaggerate age‐induced hypothalamic neuroinflammatory cytokine expression. We conclude UCP2 level and CR have different effects on IL‐1β, TNF‐α, and IL‐6 mRNA levels in the aging hypothalamus.(supported by AG19984 and R25 GM56765)