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Lipid Signaling and Synaptic Plasticity

Neuroscience Center of Excellence; School of Medicine, Louisiana State University Health Sciences Center, New Orleans

Chu Chen

Neuroscience Center of Excellence; Department of Otorhinolaryngology School of Medicine, Louisiana State University Health Sciences Center, New Orleans; Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112 cchen{at}lsuhsc.edu

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 (PGD₂, PGE₂, PGF₂, PGI₂, and TXA₂), catalyzed by cyclooxygenases (COX), are synthesized from arachidonic acid (AA). Experimental studies demonstrate that prostaglandin E₂ (PGE₂), mainly derived from the COX-2 reaction, is an important mediator, acting as a retrograde messenger via a presynaptic PGE₂ subtype 2 receptor (EP₂) 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.

Key Words: Cyclooxygenases • Prostaglandin E2 • Endocannabinoids • Prostaglandin glycerol esters • Prostaglandin ethanolamides • Long-term potentiation

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