A putative link of PUFA, GPR40 and adult-born hippocampal neurons for memory

Abstract

Long chain polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids, which are enriched in the brain, are important for multiple aspects of neuronal development and function including neurite outgrowth, signal transduction and membrane fluidity. Recent studies show that PUFA are capable of improving hippocampal long-term potentiation, learning ability of aged rats, and cognitive function of humans with memory deficits, although the underlying mechanisms are unknown.There have been several reports studying physiological roles of G-protein coupled receptor 40 (GPR40) in the pancreas, but no studies have focused on the function of GPR40 in the brain. As GPR40 was recently identified in neurons throughout the brain, it is probable that certain PUFA may act, as endogenous ligands, on GPR40 at their cell surface. However, the effects of PUFA upon neuronal functions are still not clearly understood. Here, although circumferential, a combination of in-vitro and in-vivo data is introduced to consider the effects of docosahexaenoic and arachidonic acids on brain functions. GPR40 was found in the newborn neurons of the normal and postischemic hippocampi of adult macaque monkeys, while the positive effects of PUFA upon Ca 2+ mobilization and cognitive functions were demonstrated in both GPR40 gene-transfected PC12 cells and human subjects with memory deficits. The purpose of this review is to propose a putative link among PUFA, GPR40, and hippocampal newborn neurons by discussing whether PUFA can improve memory functions through GPR40 activation of adult-born neurons. At present, little is known about PUFA requirements that make possible neurogenesis in the adult hippocampus. However, the idea that 'PUFA-GPR40 interaction might be crucial for adult neurogenesis and/or memory' should be examined in detail using various experimental paradigms.2

Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids

“…Membranes enriched in C:22 -3 PUFAs demonstrate significant increases in membrane fluidity and lipid raft formation (for review, see Stillwell and Wassall, 2003) and can directly or indirectly affect the function of a number of membrane proteins, such as receptors (Yamashima, 2008;Lafourcade et al, 2011) and ion channels (Lauritzen et al, 2000;Danthi et al, 2005;Ye et al, 2010). -3 PUFAs are also known to act as a ligand for the retinoid X receptor (RXR) and activate peroxisome proliferatoractivated receptors.…”

n−3 fatty acids prevent impairment of neurogenesis and synaptic plasticity in B-cell activating factor (BAFF) transgenic mice

“…Consumption of n −3 polyunsaturated fatty acids (n− 3 PUFAs) modulates inflammation, neurogenesis and hippocampal plasticity making these fatty acids attractive candidates for prevention and amelioration of neuropsychiatric symptoms of several autoimmune diseases (Ma et al, 2008;Robson et al, 2008;Yamashima, 2008;He et al, 2009;Kashiyae et al, 2009;Venna et al, 2009;Ma et al, 2010;Osumi, 2010). Furthermore, it has been proposed that dietary factors may contribute to the etiology and progression SLE and SjS syndrome, and that nutritional intervention may modify the severity of pathological abnormalities (Lefkowith and Klahr, 1996;Simopoulos, 2002;Cermak et al, 2003;Pestka, 2010).…”

Role of GPR40 for Fish Oil PUFA-mediated BDNF Synthesis in the Monkey Hippocampus

“…Based on our previous ischemic monkey experimental paradigms studies, we hypothesized that the post-ischemic DG tissues concomitant with up-regulation of hippocampal neurogenesis [19][20][21][22][23] might show more BDNF synthesis in vitro in response to agonists, compared to the non-ischemic DG tissues.…”

“…Since the m-BDNF synthesis was shown to be mediated by GPR40 in the non-ischemic DG tissues, the same experiments were done using the post-ischemic DG tissues to clarify whether the in vitro BDNF synthesis increases concomitant with in-vivo up-regulation of adult neurogenesis (based on our previous studies) after ischemia [19][20][21][22][23]. We focused on the post-ischemic day 7 and day 15 samples for this purpose, because newborn neurons in the monkey hippocampus showed a remarkable increase on the 2 nd week after ischemia in our previous experimental paradigm studies [19,20].…”

“…It was focused because of the two reasons; 1) Since the extent of GPR40 protein expression in the brain was much larger in primates compared to rodents [16,17,[19][20][21][22], the monkey hippocampus was appropriate for studying dynamic changes at the protein level, and 2) it showed a remarkable up-regulation of adult neurogenesis on the 2 nd week after ischemia, being in deep association with BDNF synthesis [19][20][21][22][23]. Since the PUFA-GPR40-CREB-BDNF signaling was already indicated in our ischemic monkey experimental paradigms, the monkey hippocampal tissues before and after the ischemic insult were focused for the present in vitro analysis to compare both.…”