GPR84 deficiency reduces microgliosis, but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease.

TitleGPR84 deficiency reduces microgliosis, but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2015
AuteursAudoy-Rémus, J, Bozoyan, L, Dumas, A, Filali, M, Lecours, C, Lacroix, S, Rivest, S, Tremblay, M-È, Vallières, L
JournalBrain Behav Immun
Volume46
Pagination112-20
Date Published2015 May
ISSN1090-2139
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Animals, Cognition Disorders, Dendrites, Disease Models, Animal, Gliosis, Hippocampus, Mice, Mice, Knockout, Mice, Transgenic, Microglia, Nerve Degeneration, Receptors, G-Protein-Coupled, Up-Regulation
Abstract

Microglia surrounds the amyloid plaques that form in the brains of patients with Alzheimer's disease (AD), but their role is controversial. Under inflammatory conditions, these cells can express GPR84, an orphan receptor whose pathophysiological role is unknown. Here, we report that GPR84 is upregulated in microglia of APP/PS1 transgenic mice, a model of AD. Without GPR84, these mice display both accelerated cognitive decline and a reduced number of microglia, especially in areas surrounding plaques. The lack of GPR84 affects neither plaque formation nor hippocampal neurogenesis, but promotes dendritic degeneration. Furthermore, GPR84 does not influence the clinical progression of other diseases in which its expression has been reported, i.e., experimental autoimmune encephalomyelitis (EAE) and endotoxic shock. We conclude that GPR84 plays a beneficial role in amyloid pathology by acting as a sensor for a yet unknown ligand that promotes microglia recruitment, a response affecting dendritic degeneration and required to prevent further cognitive decline.

DOI10.1016/j.bbi.2015.01.010
Alternate JournalBrain Behav. Immun.
PubMed ID25637481
Grant List / / Canadian Institutes of Health Research / Canada