Excitatory amino acids and neurodegeneration: a hypothetical role of calcium precipitation

Activation of excitatory amino acid (EAA) receptors can induce neurodegener ation by two major mechanisms of excitotoxicity, one related to the influx of Na+, Cl- and water, and the other to the increase in intracellular calci um concentration ([Ca2+](i)). Thus, acute microinjection of EAAs in several areas of the central nervous system (CNS) has been used to produce neurode generative models. We studied the excitotoxic pattern associated with acute microinjection of AMPA in rat hippocampus, medial septum-diagonal band of Broca (MS-DBB), prefrontal cortex and retina. In all cases progressive neur onal loss, glial reaction and development of intra- and extracellular calci um concretions were observed. However, a CNS-area differential vulnerabilit y was revealed, as shown by the specific atrophy of MS-DBB and its limited calcification. Whether calcium deposits are a defensive mechanism against t he massive increment of free cytoplasmatic calcium is discussed on the basi s of ultrastructural data and previous results. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved.