Open AccessCandesartan ameliorates brain inflammation associated with Alzheimer's disease
Author(s) -
Torika Nofar,
Asraf Keren,
Apte Ron N.,
FleisherBerkovich Sigal
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12802
Subject(s) - candesartan , microglia , neuroprotection , inflammation , neuroinflammation , medicine , angiotensin ii , nitric oxide , pharmacology , neuroscience , endocrinology , receptor , biology
Summary Aims Alzheimer's disease (AD) pathology is associated with brain inflammation involving microglia and astrocytes. The renin‐angiotensin system contributes to brain inflammation associated with AD pathology. This study aimed to investigate the role of candesartan, an angiotensin II type 1 receptor blocker, in modulation of glial functions associated with AD. Methods Focusing on the role of candesartan in glial inflammation, we evaluated inflammatory mediators’ levels, secreted by lipopolysaccharide‐induced microglia following candesartan treatment. Also, short‐term intranasal candesartan effects on amyloid burden and microglial activation were investigated in 5 familial AD mice. Results Candesartan showed anti‐inflammatory effects and shifted microglial activation toward a more neuroprotective phenotype. Candesartan decreased the lipopolysaccharide‐induced nitric oxide synthase and cyclooxygenase‐2 expression levels, which was accompanied by an induction of arginase‐1 expression levels and enhanced Aβ 1‐42 uptake by microglia. Moreover, intranasally administered candesartan to AD mice model significantly reduced the amyloid burden and microglia activation in the hippocampus. Conclusions These results thus shed light on the neuroprotective role of candesartan in the early stage of AD, which might relate to modulation of microglial activation states.