Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection
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,...
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Elsevier
2003-10-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996103000780 |
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author | Kay L.H Wu Samuel H.H Chan Yung-Mei Chao Julie Y.H Chan |
author_facet | Kay L.H Wu Samuel H.H Chan Yung-Mei Chao Julie Y.H Chan |
author_sort | Kay L.H Wu |
collection | DOAJ |
description | 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. |
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id | doaj.art-9a9c42008b314495bc5375a4a139f1c4 |
institution | Directory Open Access Journal |
issn | 1095-953X |
language | English |
last_indexed | 2024-12-16T16:46:08Z |
publishDate | 2003-10-01 |
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series | Neurobiology of Disease |
spelling | doaj.art-9a9c42008b314495bc5375a4a139f1c42022-12-21T22:24:10ZengElsevierNeurobiology of Disease1095-953X2003-10-011411931Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transectionKay L.H Wu0Samuel H.H Chan1Yung-Mei Chao2Julie Y.H Chan3Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, Republic of China; Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 804, Taiwan, Republic of ChinaDepartment of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, Republic of China; Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 804, Taiwan, Republic of ChinaDepartment of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, Republic of China; Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 804, Taiwan, Republic of ChinaDepartment of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, Republic of China; Center for Neuroscience, National Sun Yat-sen University, Kaohsiung 804, Taiwan, Republic of ChinaWe 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.http://www.sciencedirect.com/science/article/pii/S0969996103000780ApoptosisProinflammatory genesCytokinesCaspasesPontine reticular formationSpinal cord injury |
spellingShingle | Kay L.H Wu Samuel H.H Chan Yung-Mei Chao Julie Y.H Chan Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection Neurobiology of Disease Apoptosis Proinflammatory genes Cytokines Caspases Pontine reticular formation Spinal cord injury |
title | Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection |
title_full | Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection |
title_fullStr | Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection |
title_full_unstemmed | Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection |
title_short | Expression of pro-inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection |
title_sort | expression of pro inflammatory cytokine and caspase genes promotes neuronal apoptosis in pontine reticular formation after spinal cord transection |
topic | Apoptosis Proinflammatory genes Cytokines Caspases Pontine reticular formation Spinal cord injury |
url | http://www.sciencedirect.com/science/article/pii/S0969996103000780 |
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