Elsevier

Neurobiology of Disease

Volume 11, Issue 2, November 2002, Pages 257-274
Neurobiology of Disease

Regular Article
β-Amyloid-Induced Inflammation and Cholinergic Hypofunction in the Rat Brain in Vivo: Involvement of the p38MAPK Pathway

https://doi.org/10.1006/nbdi.2002.0538Get rights and content

Abstract

Injection into the nucleus basalis of the rat of preaggregated Aβ(1-42) produced a congophylic deposit and microglial and astrocyte activation and infiltration and caused a strong inflammatory reaction characterized by IL-1β production, increased inducible cyclooxygenase (COX-2), and inducible nitric oxide synthase (iNOS) expression. Many phospho-p38MAPK-positive cells were observed around the deposit at 7 days after Aβ injection. Phospho-p38MAPK colocalized with activated microglial cells, but not astrocytes. The inflammatory reaction was accompanied by cholinergic hypofunction. We investigated the protective effect of the selective COX-2 inhibitor rofecoxib in attenuating the inflammatory response and neurodegeneration evoked by Aβ(1-42). Rofecoxib (3 mg/kg/day, 7 days) reduced microglia and astrocyte activation, iNOS induction, and p38MAPK activation to control levels. Cholinergic hypofunction was also significantly attenuated by treatment with rofecoxib. We show here for the first time in vivo the pivotal role played by the p38MAPK microglial signal transduction pathway in the inflammatory response to the Aβ(1-42) deposit.

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    1

    To whom correspondence should be addressed. Fax: +39 055 4271 280. E-mail: [email protected].

    2

    M.G.G. and C.S. contributed equally to this paper.

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