Caspase activation contributes to delayed death of heat-stressed striatal neurons

Michael G. White, Michael Emery, Doris Nonner, John Barrett

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Hyperthermia can contribute to brain damage both during development and post-natally. We used rat embryonic striatal neurons in culture to study mechanisms underlying hyper-thermia-induced neuronal death. Heat stress at 43°C for 2 h produced no obvious signs of damage during the first 12 h after the stress, but more than 50% of the neurons died during the next 3 days. More than 40% of the neurons had activated caspases 24 h following the heat stress. Caspase-3 activity increased with a delay of. more than 10 h following cessation of the heat stress, reaching a peak at ∼18 h. Neuronal death measured 1-3 days after the stress was reduced by the general caspase inhibitors qVD-OPH (10-20 μM) and zVAD-fmk (50-100 μM). These inhibitors were protective even when added 9 h after cessation of the heat stress, consistent with the delayed activation of caspases. In contrast, blockers of Na+ channels and ionotropic glutamate receptors did not reduce the heat-induced death, indicating that glutamate excitotoxicity was not required for this neuronal death. These results show that the neuronal death produced by heat stress has characteristics of apoptosis, and that caspase inhibitors can delay this death.

Original languageEnglish
Pages (from-to)958-968
Number of pages11
JournalJournal of Neurochemistry
Volume87
Issue number4
DOIs
StatePublished - Nov 1 2003

Fingerprint

Corpus Striatum
Caspases
Neurons
Hot Temperature
Chemical activation
Caspase Inhibitors
Ionotropic Glutamate Receptors
Caspase 3
Glutamic Acid
Fever
Rats
Brain
Apoptosis

Keywords

  • Apoptosis
  • Caspase
  • Culture
  • Heat stress
  • Hyperthermia
  • Neuron

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Caspase activation contributes to delayed death of heat-stressed striatal neurons. / White, Michael G.; Emery, Michael; Nonner, Doris; Barrett, John.

In: Journal of Neurochemistry, Vol. 87, No. 4, 01.11.2003, p. 958-968.

Research output: Contribution to journalArticle

White, Michael G. ; Emery, Michael ; Nonner, Doris ; Barrett, John. / Caspase activation contributes to delayed death of heat-stressed striatal neurons. In: Journal of Neurochemistry. 2003 ; Vol. 87, No. 4. pp. 958-968.
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