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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Main Authors: Kay L.H Wu, Samuel H.H Chan, Yung-Mei Chao, Julie Y.H Chan
Format: Article
Language:English
Published: Elsevier 2003-10-01
Series:Neurobiology of Disease
Subjects:
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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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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