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 Aβ1-42 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.
Keywords: Alzheimer's disease; angiotensin II; candesartan; glial inflammation.
© 2018 John Wiley & Sons Ltd.