GPR84 deficiency reduces microgliosis, but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease.
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.
['Audoy-Rémus|Julie|J|', 'Bozoyan|Lusine|L|', 'Dumas|Aline|A|', 'Filali|Mohammed|M|', 'Lecours|Cynthia|C|', 'Lacroix|Steve|S|', 'Rivest|Serge|S|', 'Tremblay|Marie-Eve|ME|', 'Vallières|Luc|L|']
D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D000818:Animals D003072:Cognition Disorders D003712:Dendrites D004195:Disease Models, Animal D005911:Gliosis D006624:Hippocampus D051379:Mice D018345:Mice, Knockout D008822:Mice, Transgenic D017628:Microglia D009410:Nerve Degeneration D043562:Receptors, G-Protein-Coupled D015854:Up-Regulation
Chemotaxis Endotoxemia G-protein coupled receptor 84 Lipopolysaccharide Microglial cells Multiple sclerosis Neurodegeneration Neuroinflammation β-Amyloid