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Journal of Neuroscience, Vol 16, 478-485, Copyright © 1996 by Society for Neuroscience
Regulatory differences in the stress response of hippocampal neurons and glial cells after heat shock
CJ Marcuccilli, SK Mathur, RI Morimoto and RJ Miller
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637, USA.
During periods of stress, cells depend on a transient, highly conserved,
and regulated response to maintain homeostasis. This "heat shock response"
is mediated transcriptionally by a multigene family of heat shock factors
(HSF). The presence of multiple HSF suggests that activation of a given HSF
is stress-specific. Using Western blot analysis, we have demonstrated the
inability of primary cultured rat hippocampal neurons to induce a heat
shock response after hyperthermia. In contrast, secondary cultured rat
glial cells demonstrated a robust response. Examination of whole-cell
extracts from the two cell types with gel shift mobility analysis and
Western blot analysis revealed that although glial cells express HSF1 and
HSF2, hippocampal neurons only express HSF2. Incubation of whole-cell
extracts with monoclonal antisera raised against HSF1 and HSF2 before gel
shift mobility analysis demonstrated HSF1 DNA-binding activity in glial
cells and HSF2 DNA-binding activity in neurons. HSF1 has been shown to be
the principal mediator of heat-induced heat shock gene expression. These
results suggest that the deficient heat shock response of hippocampal
neurons at this developmental stage is attributable to a lack of HSF1
expression. Furthermore, these results suggest that considerations of
selective neuronal vulnerability to environmental stress should include the
principal mediators of the stress response, the HSF.
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