Neurosci Lett. 2003
Dec 15;353(1):66-8.
Increased TNFalpha production and Cox-2 activity in organotypic brain slice cultures from APPsw
transgenic mice.
Quadros A, Patel N, Crescentini R, Crawford F, Paris D, Mullan M.
Roskamp Institute,
beta-Amyloid (Abeta)
peptides are the principal component of senile plaques and vascular deposits in
Alzheimer's disease and are derived from the proteolytic
cleavage of the beta-amyloid precursor protein (APP).
We have previously shown that synthetic Abeta can
stimulate cyclooxygenase-2 (Cox-2) activity in brain organotypic
slice cultures. In the present study, we used brain slices from transgenic APP
Swedish (TgAPPsw) mice and control littermates of
different age groups to determine the effect of APP overexpression
on the levels of prostaglandin and tumor necrosis factor alpha (TNFalpha) release. The production of eicosanoid
and TNFalpha was increased as a function of age in organotypic brain slice culture from TgAPPsw
mice compared to age matched control littermates. We also showed that the selective
Cox-2 inhibitor NS-398 reduces the production of eicosanoid
and TNFalpha in organotypic
brain slice cultures of TgAPPsw mice. In conclusion,
our data suggest that either activity or expression of Cox-2 is increased in TgAPPsw mice brains as a function of age, contributing to
an increased production of pro-inflammatory eicosanoids
and TNFalpha.
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Keywords: TNFAlpha, TNF, Cox-2, organotypic, APPsw, Neuroscience