Abstract
Neuroinflammation is a key pathological component of neurodegenerative disease and is characterized by microglial activation and the secretion of proinflammatory mediators. We previously reported that a surge in prostaglandin D2 (PGD2) production and PGD2-induced microglial activation could provoke neuroinflammation. We also reported that a lipid sensor GPR120, which is expressed in intestine, could be activated by polyunsaturated fatty acids, thereby mediating secretion of glucagon-like peptide-1 (GLP-1). To reveal the relationship between PGD2-microglia-provoked neuroinflammation and intestinal PUFA/GPR120 signaling, we investigated neuroinflammation and neuronal function in GPR120 knockout (KO) mice.
In the current study, we discovered notable neuroinflammation (increased PGD2 production and microglial activation) and neurodegeneration (declines in neurogenesis, hippocampal volume, and cognitive function) in GPR120 KO mice. We also found that inhibition of PGD2 production and potentiation of GLP-1 bioactivity reduced PGD2-microglia-provoked neuroinflammation and further neurodegeneration in GPR120 KO mice.
These observations raise the possibility that intestinal GLP-1 secretion, stimulated by intestinal GPR120, may remotely contributed to suppress PGD2-microglia-provoked neuroinflammation in the hippocampus.
