Abstract
Previously, we established that persistent upregulation of c-fos expression preceded kainic acid (KA)-induced neuronal death in mice. To discriminate between events that are products of the seizures elicited by KA and those that are specifically associated with its neurotoxic actions, we have examined the expression of cellular immediate-early genes (cIEGs) following KA or pentylenetetrazol (PTZ) treatment in c-fos-lacZ transgenic rats. While both chemoconvulsants elicit seizures, only KA causes selective neuronal death. Following treatment of transgenic rats with KA there was a protracted expression of Fos-lacZ that lasted for 2-3 d. In contrast, PTZ elicited a transient increase in the transgene product that lasted about 6 hr. Normally, Fos and Fos-lacZ were detected only in neuronal nuclei. However, 6 hr following kainic acid (but not PTZ) administration, β-galactosidase activity appeared in the cytoplasm of neurons within vulnerable regions (as determined by the terminal transferase biotinylated-UTP nick end labeling (TUNEL) procedure). Like c-fos, transcripts for other cIEGs were elevated for longer periods in the KA-treated rat hippocampus. In addition, fra-1 and fra-2 were only induced in the KA-treated rat. These changes in mRNA levels were paralleled by a sustained increase in AP-1 DNA binding activity. Thus, quantitative and qualitative changes in AP-1 DNA binding complexes accompany neurotoxic cell death that are not observed following seizures.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4238-4249 |
| Number of pages | 12 |
| Journal | Journal of Neuroscience |
| Volume | 15 |
| Issue number | 6 |
| State | Published - Jun 1995 |
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Keywords
- Excitotoxicity
- Fos
- Jun
- Kainic acid
- Oxidative stress
- Pentylenetetrazol
- TUNEL
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Kainic acid-induced neuronal death is associated with DNA damage and a unique mmmediate-early gene response in c-fos-lacZ transgenic rats. / Kasof, Gary M.; Mandelzys, Allan; Maika, Shanna D.; Hammer, Robert E.; Curran, Tom; Morgan, James I.
In: Journal of Neuroscience, Vol. 15, No. 6, 06.1995, p. 4238-4249.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Kainic acid-induced neuronal death is associated with DNA damage and a unique mmmediate-early gene response in c-fos-lacZ transgenic rats
AU - Kasof, Gary M.
AU - Mandelzys, Allan
AU - Maika, Shanna D.
AU - Hammer, Robert E.
AU - Curran, Tom
AU - Morgan, James I.
PY - 1995/6
Y1 - 1995/6
N2 - Previously, we established that persistent upregulation of c-fos expression preceded kainic acid (KA)-induced neuronal death in mice. To discriminate between events that are products of the seizures elicited by KA and those that are specifically associated with its neurotoxic actions, we have examined the expression of cellular immediate-early genes (cIEGs) following KA or pentylenetetrazol (PTZ) treatment in c-fos-lacZ transgenic rats. While both chemoconvulsants elicit seizures, only KA causes selective neuronal death. Following treatment of transgenic rats with KA there was a protracted expression of Fos-lacZ that lasted for 2-3 d. In contrast, PTZ elicited a transient increase in the transgene product that lasted about 6 hr. Normally, Fos and Fos-lacZ were detected only in neuronal nuclei. However, 6 hr following kainic acid (but not PTZ) administration, β-galactosidase activity appeared in the cytoplasm of neurons within vulnerable regions (as determined by the terminal transferase biotinylated-UTP nick end labeling (TUNEL) procedure). Like c-fos, transcripts for other cIEGs were elevated for longer periods in the KA-treated rat hippocampus. In addition, fra-1 and fra-2 were only induced in the KA-treated rat. These changes in mRNA levels were paralleled by a sustained increase in AP-1 DNA binding activity. Thus, quantitative and qualitative changes in AP-1 DNA binding complexes accompany neurotoxic cell death that are not observed following seizures.
AB - Previously, we established that persistent upregulation of c-fos expression preceded kainic acid (KA)-induced neuronal death in mice. To discriminate between events that are products of the seizures elicited by KA and those that are specifically associated with its neurotoxic actions, we have examined the expression of cellular immediate-early genes (cIEGs) following KA or pentylenetetrazol (PTZ) treatment in c-fos-lacZ transgenic rats. While both chemoconvulsants elicit seizures, only KA causes selective neuronal death. Following treatment of transgenic rats with KA there was a protracted expression of Fos-lacZ that lasted for 2-3 d. In contrast, PTZ elicited a transient increase in the transgene product that lasted about 6 hr. Normally, Fos and Fos-lacZ were detected only in neuronal nuclei. However, 6 hr following kainic acid (but not PTZ) administration, β-galactosidase activity appeared in the cytoplasm of neurons within vulnerable regions (as determined by the terminal transferase biotinylated-UTP nick end labeling (TUNEL) procedure). Like c-fos, transcripts for other cIEGs were elevated for longer periods in the KA-treated rat hippocampus. In addition, fra-1 and fra-2 were only induced in the KA-treated rat. These changes in mRNA levels were paralleled by a sustained increase in AP-1 DNA binding activity. Thus, quantitative and qualitative changes in AP-1 DNA binding complexes accompany neurotoxic cell death that are not observed following seizures.
KW - Excitotoxicity
KW - Fos
KW - Jun
KW - Kainic acid
KW - Oxidative stress
KW - Pentylenetetrazol
KW - TUNEL
UR - http://www.scopus.com/inward/record.url?scp=0029025008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029025008&partnerID=8YFLogxK
M3 - Article
VL - 15
SP - 4238
EP - 4249
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 6
ER -