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

Abstract

Activation of excitatory amino acid (EAA) receptors can induce neurodegeneration by two major mechanisms of excitotoxicity, one related to the influx of Na(+), Cl(-) and water, and the other to the increase in intracellular calcium concentration ([Ca(2+)](i)). Thus, acute microinjection of EAAs in several areas of the central nervous system (CNS) has been used to produce neurodegenerative 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 neuronal loss, glial reaction and development of intra- and extracellular calcium concretions were observed. However, a CNS-area differential vulnerability was revealed, as shown by the specific atrophy of MS-DBB and its limited calcification. Whether calcium deposits are a defensive mechanism against the massive increment of free cytoplasmatic calcium is discussed on the basis of ultrastructural data and previous results.