ABSTRACT
El glutamato, principal neurotransmisor excitatorio, está involucrado en mecanismos de plasticidad sináptica, memoria y muerte neuronal o glial, y el adecuado mantenimiento de sus niveles extracelulares es esencial para evitar la excitotoxicidad. En los últimos años se han producido muchos avances en el estudio de los transportadores de glutamato (VGLUTs y EAATs) encargados de su re-captura en las sinapsis. Haremos una revisión bibliográfica de sus propiedades, alteraciones producidas por su disfunción y posibles alternativas de neuroprotección. Así mismo revisaremos otro aspecto importante, la liberación de glutamato por los astrocitos bajo diversas situaciones patológicas, descubrimiento este de las últimas décadas de investigación sobre la glia
Glutamate, the major excitatory neurotransmitter, is involved in synaptic plasticity, memory and neuronal or glial death, and it is essential to proper maintenance of extracellular levels to prevent excitotoxicity. In recent years there have been many advances in the study of glutamate transporters (EAATs and VGLUTs) responsable for its re-capture at synapses. We will do a bibliographic review of their properties, changes caused by their dysfunction and possible alternatives for neuroprotection. We will also review antoher important aspect, the release of glutamate by astrocytes under different pathological conditions, discovered on the last decades by the research on glia
Subject(s)
Humans , Astrocytes/pathology , Excitatory Amino Acid Agents , Glutamate Plasma Membrane Transport Proteins , Glutamates , Neurotransmitter Agents , Receptors, Glutamate , Vesicular Glutamate Transport Protein 1 , Vesicular Glutamate Transport ProteinsABSTRACT
Repeated exposure to morphine leads to the addiction, which influences its clinical application seriously. The glutamatergic projection from prefrontal cortex (PFC) to the nucleus accumbens (NAc) plays an important role in rewarding effects. It is still unknown whether morphine exposure changes PFC-NAc synaptic transmission. To address this question, in vivo field excitatory postsynaptic potentials (fEPSPs) induced by electric stimulating PFC-NAc projection fibers were recorded to evaluate the effect of acute morphine exposure (10 mg/kg, s.c.) on glutamatergic synaptic transmission in NAc shell of repeated saline/morphine pretreated rats. It was showed that acute morphine exposure enhanced fEPSP amplitude and reduced paired-pulse ratio (PPR) in saline pretreated rats, which could be reversed by following naloxone injection (1 mg/kg, i.p.), an opiate receptor antagonist. However, repeated morphine pretreatment significantly inhibited both the enhancement of fEPSP amplitude and reduction of PPR induced by acute morphine exposure. Those results indicate that the initial morphine exposure enhances PFC-NAc synaptic transmission by pre-synaptic mechanisms, whereas morphine pretreatment occludes this effect.
Subject(s)
Animals , Female , Rats , Excitatory Postsynaptic Potentials , Physiology , Glutamate Plasma Membrane Transport Proteins , Metabolism , Glutamates , Metabolism , Morphine , Morphine Dependence , Nucleus Accumbens , Prefrontal Cortex , Rats, Sprague-DawleyABSTRACT
Glutamate is a kind of excitatory transmitter in the central nervous system of mammals; at the same time, being with excitatory toxicity, its extracellular concentration is mainly modulated by the glutamate transporters. In the case of hypoxic-ischemia, the energy failure would lead to the generation of lactate and free radical, and to the crash of [Na+] gradient, thus exerting influence on the activity and the expression of glutamate transporters. As a result, the glutamate accumulates in the synaptic cleft, activates the glutamate receptors, and causes the death of neurons.