Neuroprotective and ameliorative actions of polyunsaturated fatty acids against neuronal diseases: implication of fatty acid-binding proteins (FABP) and G protein-coupled receptor 40 (GPR40) in adult neurogenesis.

Adult neurogenesis in the mammalian brain is well-known to occur in the subgranular zone of the hippocampus. As the hippocampus is related to learning, memory, and emotions, adult hippocampal neurogenesis possibly contributes to these functions. Adult neurogenesis is modulated by polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids that are essential for normal brain development, maintenance, and function. They are reported to improve spatial learning and memory in rodents and cognitive functions in humans. However, detailed mechanisms of PUFA effects still remain obscure. PUFA are functionally linked with chaperons called fatty acid-binding proteins (FABP). FABP uptake and transport PUFA to different intracellular organelles. Intriguingly, PUFA were determined as ligands for G protein-coupled receptor 40 (GPR40), a cell membrane receptor abundantly expressed in the brain and the pancreas of primates. While the role of GPR40 in pancreatic β-cells is associated with insulin secretion, its role in the brain is not yet clarified presumably because of its absence in the rodent brain. The purpose of this review is to discuss the role of PUFA in adult neurogenesis, considering the role of GPR40 and FABP in the hippocampal neurogenic niche. Here, the authors would like to introduce a PUFA-GPR40 signaling pathway that is specific for the primate brain.