title: GPR84 deficiency reduces microgliosis, but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease.
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.
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada.
authors: Julie
authors: J
authors: Audoy-Rémus
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada.
authors: Lusine
authors: L
authors: Bozoyan
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada.
authors: Aline
authors: A
authors: Dumas
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada.
authors: Mohammed
authors: M
authors: Filali
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada.
authors: Cynthia
authors: C
authors: Lecours
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada; Department of Molecular Medicine, Laval University, Quebec, QC, Canada.
authors: Steve
authors: S
authors: Lacroix
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada; Department of Molecular Medicine, Laval University, Quebec, QC, Canada.
authors: Serge
authors: S
authors: Rivest
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada; Department of Molecular Medicine, Laval University, Quebec, QC, Canada.
authors: Marie-Eve
authors: ME
authors: Tremblay
authors: Axis of Neuroscience, University Hospital Center of Quebec, Quebec, QC, Canada; Department of Molecular Medicine, Laval University, Quebec, QC, Canada. Electronic address: Luc.Vallieres@crchul.ulaval.ca.
authors: Luc
authors: L
authors: Vallières
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005911:Gliosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; C507114:Gpr84 protein, mouse; D043562:Receptors, G-Protein-Coupled
keywords: Chemotaxis; Endotoxemia; G-protein coupled receptor 84; Lipopolysaccharide; Microglial cells; Multiple sclerosis; Neurodegeneration; Neuroinflammation; β-Amyloid