Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection

Kay L.H. Wu, Samuel H.H. Chan, Yung Mei Chao, Julie Y.H. Chan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

40 Scopus citations

Abstract

We identified apoptotic neurons in pontine reticular formation (PRF), the origin of pontine reticulospinal fibers, in adult Sprague-Dawley rats after complete spinal cord transection (SCT) at T8 level. SCT also increased the expression in PRF of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, caspase-1, or caspase-3 mRNA. This was followed by an augmented expression of activated caspase-3 protein, an increase in caspase-3 activity, and expression of a cleaved fragment of poly(ADP-ribose) polymerase (PARP), a proteolytic substrate of the activated caspase-3. Microinjection bilaterally into the PRF of an antiserum against TNF-α attenuated the expression of IL-6 mRNA and up-regulation of caspase-3 mRNA, and a caspase-3 inhibitor, DEVD-CHO, suppressed the augmentation in activated caspase-3 or cleaved PARP expression after SCT. Both treatments also reduced the number of SCT-induced apoptotic PRF neurons. We conclude that PRF neurons in adult mammalian brain may actively degrade themselves after SCT through apoptosis, via signaling processes that involve activation of proinflammatory cytokine genes and the intracellular caspase-3 pathway.

Original languageEnglish
Pages (from-to)19-31
Number of pages13
JournalNeurobiology of Disease
Volume14
Issue number1
DOIs
StatePublished - 10 2003
Externally publishedYes

Keywords

  • Apoptosis
  • Caspases
  • Cytokines
  • Pontine reticular formation
  • Proinflammatory genes
  • Spinal cord injury

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