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Role of exercise in the regulation of NF‐kappaB‐dependent gene expression in Alzheimer's Disease‐affected brain
Author(s) -
Lloyd Jesse William,
BeamanHall Carol,
Heckstall Ebony Monique,
Vallano MaryLou,
Keslacy Stefan
Publication year - 2010
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.24.1_supplement.1053.2
Subject(s) - downregulation and upregulation , inflammation , neuroinflammation , nf κb , immune system , hippocampus , gene expression , endocrinology , medicine , chemistry , neuroscience , immunology , biology , gene , biochemistry
A defining feature of Alzheimer's disease (AD) is plaque deposition induced by accumulation of Amyloid beta peptides (Aβ) that trigger chronic inflammation in the brain. Aβ‐related neurodegenerative changes are improved by chronic exercise. NF‐κB pathway is a “master controller” of the inflammatory process. Hypothesis: We hypothesize that exercise will diminish the AD‐associated NF‐κB activation in the brain. Aβ‐related model of AD APP/PS1 and wild‐type (WT) mice were exposed to voluntary running for 1 month (EX) and compared to sedentary (SED). Results EX demonstrated a decrease in plaque count. Using a qRT‐PCR array, we observed that exercise induced a downregulation of inflammatory genes, (IL‐1α, IL‐1β, Ltbr Tlr1/8/9/, Trfrs10b, Tnfrsf1a and Traf3) and an upregulation of anti‐inflammatory genes (Ccl2, IFNγ, Cd27, Card10 and IFNγ) associated with NF‐κB in hippocampus (Hip) of SED APP/PS1 mice. AD‐induced expression and phosphorylation of NF‐κB/P65 were diminished in Hip, cerebellum (Cb) and cortex (Cx) of EX. Phospho‐IKKα/β levels were reduced in Hip of EX compare to SED. P65, physically bound to IκB, was sequestrated into the cytoplasm following exercise. Conclusion The molecular mechanisms underlying the beneficial effect of exercise in AD‐affected brain may rely on i) P65/IκB physical interaction and ii) regulation of the immune system through IFNγ signaling.