Fatty Acids as Regulators of Hippocampal Neurogenesis: the Case of Gpr40

The hippocampus of adult mammals including humans continues to generate neurons throughout life. The neural stem/progenitor cells, the cellular phenotype responsible for this regenerative capacity, are a subject of intensive research focused on the mechanisms of their regulation. Intriguing recent data implicate an unexpected molecular player in this regulation: free fatty acids. Polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids were identified to act on the pancreas via a novel receptor, named G-protein coupled receptor 40 (GPR40). However, the pancreas appears not to be the single target organ of PUFA/GPR40 actions. Very recent findings have discovered GPR40 expression in the hippocampal dentate gyrus, including its progenitor cell niche responsible for neuronal renewal throughout life. These data open a possibility that PUFA may regulate adult hippocampal neurogenesis and thus become a therapeutic tool to treat neurological disorders in humans. Biomed Rev 2007; 18: 69-73.