The mode of spinal motor neurons degeneration in a model of slow glutamate excitotoxicity in vitro.

Abstract

The defective glial and/or neuronal glutamate transport may, in chronic neurotoxicity, contribute to several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS)--a progressive neurodegenerative disorder of lower and upper motor neurons (MNs). To determine the detailed ultrastructural characteristics of excitotoxic motor neurons neurodegeneration we used a model of slow excitotoxicity in vitro based on selective inhibition of glutamate uptake. The study was performed on organotypic cultures of the rat lumbar spinal cord subjected to various concentrations of glutamate uptake blockers: threohydroxyaspartate (THA) and L-trans-pyrrolidine-2, 4-dicarboxylate (PDC). The chronic inhibition of glutamate transport resulted in a dose-dependent slow neurodegeneration of spinal MNs consisting of necrotic, apoptotic and autophagic mode of cell death. There were some MNs that shared certain characteristics of a different type of cell injury. The results showed that a different mode of cell death in excitotoxic MNs degeneration may coexist resulting in apoptosis-necrosis and apoptosis-autophagocytosis continuum.