Lipid Signaling and Synaptic Plasticity

Abstract

Lipids are essential components of plasma- and organelle-membranes, not only providing a frame for embedded proteins (e.g., receptors and ion channels) but also functioning as reservoirs for lipid mediators. Increasing evidence indicates that bioactive lipids such as eicosanoids, endocannabinoids, and lysophospholipids serve as intercellular and intracellular signaling molecules participating in physiological and pathological functions in the brain. The discovery of some of these lipid receptors and novel lipid signaling mediators has sparked an intense interest in lipidomic neurobiology research. Classic prostaglandins (PGD(2), PGE(2), PGF(2alpha), PGI(2), and TXA(2)), catalyzed by cyclooxygenases (COX), are synthesized from arachidonic acid (AA). Experimental studies demonstrate that prostaglandin E(2) (PGE(2)), mainly derived from the COX-2 reaction, is an important mediator, acting as a retrograde messenger via a presynaptic PGE(2) subtype 2 receptor (EP(2)) in modulation of synaptic events. Novel prostaglandins (prostaglandin glycerol esters and prostaglandin ethanolamides) are COX-2 oxidative metabolites of endogenous cannabinoids (2-arachidonyl glycerol and arachidonyl ethanolamide). Recent evidence suggests that these new types of prostaglandins are likely novel signaling mediators involved in synaptic transmission and plasticity. This means that COX- 2 plays a central role in metabolisms of AA and endocannabinoids (eCBs) and productions of AA- and eCB- derived prostaglandins. Thus, in the present review article, the authors will mainly discuss COX-2 regulation of prostaglandin signaling in modulation of hippocampal synaptic transmission and plasticity.

HCN Pacemaker Channel Activation Is Controlled by Acidic Lipids Downstream of Diacylglycerol Kinase and Phospholipase A2

“…Given the significant contribution of I H to the subthreshold behavior of many cells in both the CNS and periphery (including the PNS, heart, and smooth muscle), our evidence that the voltage dependence of HCN channels is sensitive to AA and PA opens up avenues of investigation in a number of realms, including synaptic transmission (Sang and Chen, 2006), neuropathic pain (Woolf and Salter, 2000;Chaplan et al, 2003), and cardiac ischemia (Mancuso et al, 2003), in which both I H and changes in these metabolites have been independently implicated.…”

A neuroscientist's guide to lipidomics

“…These lipids can be further modified by oxygen-adding enzymes (for example, prostaglandin-endoperoxide synthases) (fIG. 4), forming a family of paracrine signals called eicosanoids 35 . Notably, most of the lipids listed above can also be produced through alternative routes -for example, phosphatidic acid by phospholipase D acting on phosphatidylcholine (fIG.…”

“…There are many variations of this theme, but most of them entail the creation of lipid molecules that remain transiently associated with the membrane in which they originate: two familiar examples are the stimulus-dependent activations of phosphatidylinositol kinases to produce PI(4,5)P 2 and of phospholipases A 2 to mobilize arachidonic acid from glycerophospholipids 34,35 .…”

Changes in Cyclooxygenase-2 Immunoreactivity in the Hippocampus in a Model of Streptozotocin-Induced Type 1 Diabetic Rats

“…COX-2's action is involved with various prostaglandins [28], cell cycle proteins [23] and the NMDA receptor [19]. Still, COX-2's roles in neurogenesis are not fully elucidated and it can behave like a double-edged sword with positive or negative effect.…”

“…One of possible actions of COX-2 is on cell cycle proteins. COX-2 showed a positive effect on proliferation of neural progenitor cells and synaptic plasticity [28]. COX-2 inhibition is related with memory impairment and COX-2 knockouts showed reduced hippocampal neurogenesis [31].…”