Abstract
Whereas status epilepticus, or the condition of continuous epileptic seizures, produces a characteristic pattern of preferential neuronal cell loss in the hippocampus, the underlying mechanism is still unsettled. Based on an experimental model of temporal lobe status epilepticus, we demonstrated previously that prolonged seizures prompted an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield, followed by the activation of mitochondrial apoptotic signaling cascade. Using the same animal model, the present study evaluated the hypothesis that transcriptional upregulation of NOS II gene by nuclear factor-κB (NF-κB) promotes apoptotic neuronal cell death in the hippocampus following status epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound translocation of NF-κB p50 and p65 subunits and DNA binding activity of NF-κB were observed in hippocampal CA3 neurons as early as 30 min after elicitation of sustained seizure activity by microinjection of kainic acid into the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In addition, application bilaterally into the hippocampal CA3 subfield of a selective NF-κB inhibitor, pyrrolidine dithiocarbamate or double-stranded κB decoy DNA significantly antagonized the activated NOS II-peroxynitrite signaling cascade (3 hr) and the associated manifestations of apoptotic cell death (7 days) in the hippocampus. We conclude that activation of NF-κB in hippocampal CA3 neurons upregulates NOS II gene expression following experimental temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the hippocampus.
| Original language | English |
|---|---|
| Pages (from-to) | 1898-1907 |
| Number of pages | 10 |
| Journal | Journal of Neuroscience Research |
| Volume | 88 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2010 Jul 1 |
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All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
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Transcriptional upregulation of nitric oxide synthase II by nuclear factor-κB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus. / Chuang, Yao Chung; Chen, Shang Der; Lin, Tsu Kung; Chang, Wen Neng; Lu, Cheng Hsien; Liou, Chia Wei; Chan, Samuel H.H.; Zhang, Ya-Wen.
In: Journal of Neuroscience Research, Vol. 88, No. 9, 01.07.2010, p. 1898-1907.Research output: Contribution to journal › Article
TY - JOUR
T1 - Transcriptional upregulation of nitric oxide synthase II by nuclear factor-κB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus
AU - Chuang, Yao Chung
AU - Chen, Shang Der
AU - Lin, Tsu Kung
AU - Chang, Wen Neng
AU - Lu, Cheng Hsien
AU - Liou, Chia Wei
AU - Chan, Samuel H.H.
AU - Zhang, Ya-Wen
PY - 2010/7/1
Y1 - 2010/7/1
N2 - Whereas status epilepticus, or the condition of continuous epileptic seizures, produces a characteristic pattern of preferential neuronal cell loss in the hippocampus, the underlying mechanism is still unsettled. Based on an experimental model of temporal lobe status epilepticus, we demonstrated previously that prolonged seizures prompted an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield, followed by the activation of mitochondrial apoptotic signaling cascade. Using the same animal model, the present study evaluated the hypothesis that transcriptional upregulation of NOS II gene by nuclear factor-κB (NF-κB) promotes apoptotic neuronal cell death in the hippocampus following status epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound translocation of NF-κB p50 and p65 subunits and DNA binding activity of NF-κB were observed in hippocampal CA3 neurons as early as 30 min after elicitation of sustained seizure activity by microinjection of kainic acid into the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In addition, application bilaterally into the hippocampal CA3 subfield of a selective NF-κB inhibitor, pyrrolidine dithiocarbamate or double-stranded κB decoy DNA significantly antagonized the activated NOS II-peroxynitrite signaling cascade (3 hr) and the associated manifestations of apoptotic cell death (7 days) in the hippocampus. We conclude that activation of NF-κB in hippocampal CA3 neurons upregulates NOS II gene expression following experimental temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the hippocampus.
AB - Whereas status epilepticus, or the condition of continuous epileptic seizures, produces a characteristic pattern of preferential neuronal cell loss in the hippocampus, the underlying mechanism is still unsettled. Based on an experimental model of temporal lobe status epilepticus, we demonstrated previously that prolonged seizures prompted an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield, followed by the activation of mitochondrial apoptotic signaling cascade. Using the same animal model, the present study evaluated the hypothesis that transcriptional upregulation of NOS II gene by nuclear factor-κB (NF-κB) promotes apoptotic neuronal cell death in the hippocampus following status epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound translocation of NF-κB p50 and p65 subunits and DNA binding activity of NF-κB were observed in hippocampal CA3 neurons as early as 30 min after elicitation of sustained seizure activity by microinjection of kainic acid into the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In addition, application bilaterally into the hippocampal CA3 subfield of a selective NF-κB inhibitor, pyrrolidine dithiocarbamate or double-stranded κB decoy DNA significantly antagonized the activated NOS II-peroxynitrite signaling cascade (3 hr) and the associated manifestations of apoptotic cell death (7 days) in the hippocampus. We conclude that activation of NF-κB in hippocampal CA3 neurons upregulates NOS II gene expression following experimental temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the hippocampus.
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U2 - 10.1002/jnr.22369
DO - 10.1002/jnr.22369
M3 - Article
VL - 88
SP - 1898
EP - 1907
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
SN - 0360-4012
IS - 9
ER -