Neutralization of IL-17 rescues amyloid-?-induced neuroinflammation and memory impairment.

ABSTRACT: BACKGROUND AND PURPOSE:Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies. However, the role of the cytokine, IL-17 has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by i.c.v. or intranasal (IN) routes on amyloid-? (A?)-induced neuroinflammation and memory impairment in mice. EXPERIMENTAL APPROACH:A?1-42 was injected into cerebral ventricles of adult CD1 mice. These mice received IL-17Ab via i.c.v. either at 1 h prior to A?1-42 injection or IN 5 and 12 days after A?1-42 injection. After 7 and 14 days of A?1-42 administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas. KEY RESULTS:Pretreatment with IL-17Ab, given, i.c.v., markedly reduced A?1-42 -induced neurodegeneration, improved memory function, and prevented the increase of pro-inflammatory mediators in a dose-dependent manner at 7 and 14 days. Similarly, the double IN administration of IL-17Ab after A?1-42 injection reduced neurodegeneration, memory decline, and the levels of proinflammatory mediators and cytokines. CONCLUSION AND IMPLICATIONS:These findings suggest that the IL-17Ab reduced neuroinflammation and behavioural symptoms induced by A?. The efficacy of IL-17Ab IN administration in reducing A?1-42 neurodegeneration points to a possible future therapeutic approach in patients with AD. LINKED ARTICLES:This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.

SUBMITTER: Cristiano C 

PROVIDER: S-EPMC6715610 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature