Search

There is increasing evidence that so-called "autophagic cell death" participates in cell degeneration in certain pathological conditions. Autophagy might be involved in some neurodegenerative processes, including lateral amyotrophic sclerosis (SLA). The exact mechanism leading to progressive motor neuron (MN) loss remains unclear, but glutamate-mediated mechanism is thought to be responsible. Previous ultrastructural studies by the authors performed on a model of SLA in vitro, based on chronic glutamate excitotoxicity, revealed a subset of morphological features characteristic to different modes of neuronal death, including autophagic degeneration. The contribution of this pathway of MNs death is evaluated in organotypic cultures of rat lumbar spinal cord chronically exposed to specific glutamate uptake blockers: DL-threo-beta-hydroxyaspartate (THA) and L-transpyrrolidine-2,4-dicarboxylate (PDC). The study documents the various steps of authophagy in slowly evolving process of MN neurodegeneration. The cells undergoing autophagy usually exhibited sequestration of some parts of cytoplasm with normal and/or degenerated organelles, whereas other parts of cytoplasm as well as neuronal nucleus remained unchanged. The advanced autophagic changes were often associated with other modes of MN death, especially with apoptosis. Numerous MNs revealed apoptotic nuclear features with typical peripheral margination of nuclear chromatin, accompanied by severe autophagic or autophagic-necrotic degeneration of the cytoplasm. These results support the opinion of unclear distinction between different modes of cell death and indicate the involvement of autophagey in MNs neurodegeneration in vitro.

Zinc is one of the trace elements playing an important role in many fundamental biological processes. However, it is also one of the possible etiological agents involved in nerve cell damage in certain human neurodegenerative disorders. The precise mechanism of neuroprotective ability of Zn against neurotoxicity evidenced in various pathological conditions remains unclear, especially concerning the intrinsic potential toxicity of this metal. This ultrastructural study was undertaken to determine the effect of zinc on the evolution of anoxia-induced neuronal injury in the organotypic cultures of rat hippocampus. The in vitro model of oxygen deprivation was produced by maintaining the cultures in a pure nitrogen atmosphere in flask adapted for permanent gas flow for 20 min. The selected cultures were pretreated with micromolar concentration of ZnCl2 (25-500 microM) at 30 min prior anoxia. The ultrastructural findings documented that Zn exhibited dose-dependent ability to reduce anoxia-induced neuronal changes in hippocampal neurons in vitro. Zn at a concentration of 100 microM was able to significantly protect the hippocampal formation against the development of late apoptotic changes, whereas the early necrotic anoxia-induced neuronal injury was not so efficiently reduced.