TY - JOUR
T1 - Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection
AU - Wu, Kay L.H.
AU - Chan, Samuel H.H.
AU - Chao, Yung Mei
AU - Chan, Julie Y.H.
PY - 2003/10
Y1 - 2003/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Caspases
KW - Cytokines
KW - Pontine reticular formation
KW - Proinflammatory genes
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=0042334600&partnerID=8YFLogxK
U2 - 10.1016/S0969-9961(03)00078-0
DO - 10.1016/S0969-9961(03)00078-0
M3 - 文章
C2 - 13678663
AN - SCOPUS:0042334600
SN - 0969-9961
VL - 14
SP - 19
EP - 31
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -