‘PUFA–GPR40–CREB signaling’ hypothesis for the adult primate neurogenesis

Somebody needs to tell us how much saturated fat we should have in our system to allow neurogenesis.
http://www.sciencedirect.com/science/article/pii/S0163782712000173

Abstract

Despite the well-known effects of polyunsaturated fatty acids (PUFA) on synaptic plasticity, PUFA-modulated signaling mechanism is unknown especially in humans. In 2003, three groups reported that G protein-coupled receptor 40 (GPR40) induces Ca²⁺ mobilization in response to PUFA. Although GPR40 gene is abundantly expressed in the primate brain, it is negligible in the rodent brain. Diverse PUFA including docosahexaenoic acid (DHA) are in vitro ligands for GPR40, but nobody knows its downstream pathway. cAMP-response element binding protein (CREB) is a transcription factor transmitting extracellular signals to change gene expression. Although PUFA, transported by fatty acid binding proteins (FABP), directly phosphorylate CREB in rodents, hydrophobic PUFA cannot access to the nuclei in the primate neurons because of lack of a cargo protein. Ischemia-enhanced adult neurogenesis in monkeys showed concomitant upregulation of GPR40 and phosphorylated CREB, and localization of both in the neurogenic niche. Here, ‘PUFA–GPR40–CREB signaling’ hypothesis was highlighted as a regulator of adult neurogenesis specific for primates.

Abbreviations

• AC, adenylyl cyclase;
• AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid;
• ARA, arachidonic acid;
• BDNF, brain-derived neurotrophic factor;
• BrdU, bromodeoxyuridine;
• [Ca²⁺]_i, intracellular Ca²⁺ concentration;
• CaMK, calmodulin-dependent kinase;
• cAMP, cyclic AMP;
• CRE, cAMP response element;
• CREB, cAMP response element-binding protein;
• cPLA₂, cytosolic phospholipase A₂;
• DAG, diacylglycerol;
• DCX, doublecortin;
• DG, dentate gyrus;
• DGLA, dihomogammalinolenic acid;
• DHA, docosahexaenoic acid;
• EDTA, ethylenediamine tetraacetic acid;
• EPA, eicosapentaenoic acid;
• ER, endoplasmic reticulum;
• FABP, fatty acid binding proteins;
• GAP-43, growth-associated protein-43;
• GCL, granular cell layer;
• GPCR, G protein-coupled receptors;
• GPR40, G protein-coupled receptor 40;
• Gαq, G protein α-subunit of the Gq family;
• Gq, G protein of the Gq family;
• IGF, insulin-like growth factor;
• IP₃, inositol 1,4,5-trisphosphate;
• iPLA₂, Ca²⁺-independent phospholipase A₂;
• LT, leukotriene;
• LTP, long-term potentiation;
• MAPK, mitogen-activated protein kinase;
• NFκB, nuclear factor κB;
• NGF, nerve growth factor;
• NHR, nuclear hormone receptors;
• NMDA, N-methyl-d-aspartate;
• pCREB, phosphorylated cAMP response element-binding protein;
• PG, prostaglandin;
• PGI, prostacyclin;
• PIP₂, phosphatidylinositol 4,5-bisphosphate;
• PKA, protein kinase A;
• PKC, protein kinase C;
• PPAR, peroxysome proliferator-activated receptors;
• PS, phosphatidylserine;
• PLA₂, phospholipase A₂;
• PLC, phospholipase C;
• PPAR, peroxisome proliferator-activated receptors;
• PSA–NCAM, polysialylated–neural cell adhesion molecule;
• PUFA, polyunsaturated fatty acids;
• RXR, retinoid X receptors;
• SGZ, subgranular zone;
• SNARE, soluble N-ethylmaleimide-sensitive-factor attachment protein receptor;
• TrkB, neurotrophin tyrosine kinase receptor type 2;
• TXA, thromboxane;
• VEGF, vascular endothelial growth factor

Keywords

• Adult neurogenesis;
• Hippocampus;
• Primate;
• PUFA;
• GPR40;
• CREB;
• BDNF