Resumen
L-Glutamic acid (Glu) is accepted as the major excitatory neurotransmitter in the nervous system, although other acidic amino acids such as L-aspartic acid and L-homocysteic acid may also participate (1). Nevertheless, ongoing research reveals that the functions of Glu are much more diverse and complex than simply generating excitatory postsynaptic currents (EPSCs). It plays a major role in brain development, affecting neuronal migration, neuronal differentiation, axon genesis, and neuronal survival (2–4). In the mature nervous system, Glu is central to neuroplasticity, in which there are use-dependent alterations in synaptic efficacy as well as changes in synaptic structure. These latter actions are intimately implicated in memory and related cognitive functions. Finally, persistent or overwhelming activation of glutamate-gated ion channels can cause neuronal degeneration (5) depending on the circumstances, this occurs by means of necrosis or apoptosis (6). Known as ‘‘excitotoxicity,’’ this phenomenon has been linked to the final common pathway of neuronal death in a range of disorders including Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and stroke (7,8).
This chapter provides an overview of the physiology and pharmacology of brain glutamatergic systems. There is a special emphasis on glutamate receptors because their rich diversity confers physiologic and pharmacologic specificity for this single neurotransmitter, which is used by up to 40% of all brain synapses. Finally, the potential role of glutamatergic system dysfunction in the pathophysiology of neuropsychiatric disorders is addressed.
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