Increased Expression of IL-1beta Converting Enzyme in Hippocampus after Ischemia: Selective Localization in Microglia

Although the interleukin-1beta converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell death in vitro and in ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this question, we examined the...

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Bibliographic Details
Published in:The Journal of neuroscience 1996-07, Vol.16 (13), p.4146-4154
Main Authors: Bhat, Ratan V, DiRocco, Richard, Marcy, Val R, Flood, Dorothy G, Zhu, Yuan, Dobrzanski, Pawel, Siman, Robert, Scott, Richard, Contreras, Patricia C, Miller, Matthew
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Base Sequence
Brain Ischemia - enzymology
Caspase 1
Cysteine Endopeptidases - genetics
Cysteine Endopeptidases - metabolism
Gerbillinae
Hippocampus - enzymology
Hippocampus - pathology
Immunohistochemistry
Male
Microglia - enzymology
Molecular Probes - genetics
Molecular Sequence Data
Neurons - pathology
RNA, Messenger - metabolism
Time Factors
Tissue Distribution
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Summary:Although the interleukin-1beta converting enzyme (ICE)/CED-3 family of proteases has been implicated recently in neuronal cell death in vitro and in ovo, the role of specific genes belonging to this family in cell death in the nervous system remains unknown. To address this question, we examined the in vivo expression of one of these genes, Ice, after global forebrain ischemia in gerbils. Using RT-PCR and Western immunoblot techniques, we detected an increase in the mRNA and protein expression of ICE in hippocampus during a period of 4 d after ischemia. Chromatin condensation was observed in CA1 neurons within 2 d after ischemia. Internucleosomal DNA fragmentation and apoptotic bodies were observed between 3 and 4 d after ischemia, a period during which CA1 neuronal death is maximal. In nonischemic brains, ICE-like immunoreactivity was relatively low in CA1 pyramidal neurons but high in scattered hippocampal interneurons. After ischemia, ICE-like immunoreactivity was not altered in these neurons. ICE-like immunoreactivity, however, was observed in microglial cells in the regions adjacent to the CA1 layer as early as 2 d after ischemic insult. The increase in ICE-like immunoreactivity was robust at 4 d after ischemia, a period that correlates with the DNA fragmentation observed in hippocampal homogenates of ischemic brains. These results provide the first evidence for the localization and induction of ICE expression in vivo after ischemia and suggest an indirect role for ICE in ischemic damage through mediation of an inflammatory response.
ISSN:0270-6474
1529-2401