What synaptic lipid signaling tells us about XXXX -induced damage and epileptogenesis.

@entity1 @entity410 @entity2227 @entity1024 @entity75 @entity1426 @entity9294 @entity4176 @entity3900 @entity140 @entity143 @entity460 @entity1813 @entity528
@entity2227 , the most abundant excitatory neurotransmitter in the @entity1 CNS, plays a central role in many neuronal functions, such as long-term potentiation, which is necessary for learning and memory formation. The fast excitatory @entity2227 neurotransmission is mediated by ionotropic receptors that include @entity140 / @entity4176 and @entity1024 ( @entity143 ) receptors, while the slow @entity2227 responses are mediated through its interaction with metabotropic receptors (mGluRs) coupled to G-proteins. During @entity410 , massive release of @entity2227 underlies excitotoxic @entity528 as it triggers an overflow of @entity460 in postsynaptic neurons mediated by @entity143 -gated channels. The early upstream postsynaptic events involve the activation of phospholipases, with the release of membrane-derived signaling molecules, such as free @entity1426 (AA), @entity1813 , and platelet-activating factor (PAF). These bioactive lipids modulate the early neuronal responses to stimulation as they affect the activities of ion channels, receptors, and enzymes; and when released into the extracellular space, they can contribute to the modulation of presynaptic neurotransmitter release/re-uptake, and/or affect other neighboring neuronal/glial cells. The downstream postsynaptic events target the nucleus, leading to activation of gene-expression cascades. Syntheses of new proteins are the basis for @entity410 -induced sustained physiological and/or pathological changes that occur hours, days, or months later, such as synaptic reorganization and repair, and apoptotic/necrotic @entity528 . The intricate mesh of signaling pathways converging to the nucleus, and connecting upstream to downstream synaptic events, are at present the focus of many research efforts. We describe in this chapter how @entity410 -induced @entity2227 release activates the hydrolysis of membrane AA-phospholipids via @entity3900 ( @entity3900 ), @entity9294 , and PLD, thus releasing bioactive lipids that, in turn, modulate neurotransmission. We discuss mechanisms through which lipid messengers, such as AA and PAF, may turn into injury mediators participating in @entity410 -induced @entity75 .
