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Dying neural cells activate glia through the release of a protease product
Author(s) -
Viviani Barbara,
Corsini Emanuela,
Galli Corrado L.,
Padovani Alessandro,
Ciusani Emilio,
Marinovich Marina
Publication year - 2000
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/1098-1136(200010)32:1<84::aid-glia80>3.0.co;2-q
Subject(s) - gliosis , neuroglia , biology , neurotoxicity , neurodegeneration , astrocyte , neuroscience , microbiology and biotechnology , hippocampal formation , microglia , glial fibrillary acidic protein , tumor necrosis factor alpha , pathology , immunology , central nervous system , inflammation , medicine , disease , immunohistochemistry , toxicity
The close relationship between neurodegeneration and gliosis could play a relevant role in propagating the degenerative event in the brain. Although there is evidence of the neurotoxicity of activated glia, the ability of damaged neurons to modulate glial response remains unexplored. Exposure of primary glial cells to damaged or dead hippocampal neurons was followed by glial release of tumor necrosis factor‐α (TNF‐α). This release was reduced by a partial prevention of neural death. By contrast, no TNF‐α was released when glial cells were exposed to damaged murine fibroblasts. Exposure of glial cells to the cerebrospinal fluid (CSF) of patients with Alzheimer's disease was also followed by TNF‐α release, while the CSF of subjects with nondegenerative brain disorders evoked no response. These data suggest that damaged neurons both in vitro and in vivo release factor(s) that activate glial response. Heat treatment of sonicated neurons or use of a mixture of protease inhibitors, among them the caspase inhibitors Z‐DEVD‐FMK and Z‐YVAD‐FMK, prevented TNF‐α release from glial cells. We conclude that a primary neurodegenerative event may induce glial response by releasing a neurospecific protein factor via activation of a caspase. GLIA 32:84–90, 2000. © 2000 Wiley‐Liss, Inc.