Submitted on August 1, 2003
Revised on September 2, 2003
Accepted on September 5, 2003
Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor
Nicolas G. Bazan
Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112
Corresponding Author: nbazan{at}lsuhsc.edu
The highly networked organization of the nervous system encompasses a variety of cells that display, as a distinctive feature, one of the largest membrane surface areas of all cells. This would be very clearly illustrated if the plasma membrane from a neuron (e.g., hippocampal CA1 or Purkinje cell of the cerebellum) could be spread out on a flat surface: the branching and complexities of dendrites that form the dendritic spines are very extensive, largely comprising postsynaptic elements. An important additional feature of neuronal dendrites is that they undergo dramatic changes in shape and length during development and learning; they are also affected in aging and in several pathologic conditions. Astrocytes, oligodendrocytes, and microglial cells have very large plasma membrane surface areas as well. To add a further level of complexity, all of these cells extensively interact with neurons. How membranes are organized has conceptually evolved from the lipid bilayer with embedded proteins to a highly dynamic, heterogeneous patchwork of microdomains that contain ion channels, receptors, transporters, and other proteins. Cellular membranes in the nervous system were divided in the past into relatively more fluid membranes (e.g., those of cells of gray matter) and relatively more rigid membranes (e.g., oligodendrocyte plasma membrane that spirals around the axon to form the myelin), according to the higher or lower content of polyunsaturated fatty acids (PUFA) in phospholipids. Currently in neurons, glia, and endothelial cells of the cerebrovasculature, several phospholipid pools are increasingly being recognized as reservoirs of lipid messengers. Specific lipid messengers are cleaved from these reservoir phospholipids by phospholipases upon stimulation by neurotransmitters, neurotrophic factors, cytokines, membrane depolarization, ion channel activation, etc. Lipid messengers regulate and interact with multiple other signaling cascades, contributing to the development, differentiation, function, protection, and repair of the cells of the nervous system.
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