Abstract
Phosphorylation of the DNA-binding transcription factor, cyclic AMP response element binding protein (CREB), was immunohistochemically examined in rat brain hippocampal CA1 in order to examine the ischemic vulnerability of this region from the viewpoint of CREB activation. The rat brain had been subjected to 90-min focal ischemia followed by various periods of recirculation. Focal ischemia was induced by occlusion of the middle cerebral artery using the intraluminal suture method. CA1 pyramidal neurons in the sham animals showed definite immunoreactivity with anti-CREB antibody, which binds to both unphosphorylated and phosphorylated CREB, while reactivity with anti-phosphorylated CREB antibody was barely detectable in these neurons. In contrast, at 3.5 h of recirculation, a significant increase in the number of phosphorylated CREB-positive neurons was noted in the CA1 on both sides, and the increase continued until 48 h of recirculation with a tendency for gradual decline. At each period, the ischemic side showed a more marked increase in the number of immunoreactive cells as compared to the nonischemic side. Cresyl violet staining revealed CA1 pyramidal neurons to be maintained intact until 14 day of recirculation, at which time CREB phosphorylation has returned to the control level. Transient global ischemia is known to induce only mild CREB phosphorylation in the CA1 followed by a frank neuronal loss in this region. These data suggest that CREB phosphorylation can be persistently activated in CA1 neurons after focal ischemia and that this phenomenon may be closely associated with protection of these neurons. (C) 2000 Academic Press.
| Original language | English |
|---|---|
| Pages (from-to) | 462-471 |
| Number of pages | 10 |
| Journal | Experimental Neurology |
| Volume | 161 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2000 Feb |
Fingerprint
Keywords
- Cerebral ischemia
- CREB
- Cyclic AMP response element binding protein
- Hippocampal CA1
- Neuroprotection
- Pyramidal neuron
- Recirculation
ASJC Scopus subject areas
- Neurology
- Neuroscience(all)
Cite this
Persistent CREB phosphorylation with protection of hippocampal CA1 pyramidal neurons following temporary occlusion of the middle cerebral artery in the rat. / Tanaka, Kortaro; Nogawa, Shigeru; Nagata, Eiichiro; Ito, Daisuke; Suzuki, Shigeaki; Dembo, Tomohisa; Kosakai, Arifumi; Fukuuchi, Yasuo.
In: Experimental Neurology, Vol. 161, No. 2, 02.2000, p. 462-471.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Persistent CREB phosphorylation with protection of hippocampal CA1 pyramidal neurons following temporary occlusion of the middle cerebral artery in the rat
AU - Tanaka, Kortaro
AU - Nogawa, Shigeru
AU - Nagata, Eiichiro
AU - Ito, Daisuke
AU - Suzuki, Shigeaki
AU - Dembo, Tomohisa
AU - Kosakai, Arifumi
AU - Fukuuchi, Yasuo
PY - 2000/2
Y1 - 2000/2
N2 - Phosphorylation of the DNA-binding transcription factor, cyclic AMP response element binding protein (CREB), was immunohistochemically examined in rat brain hippocampal CA1 in order to examine the ischemic vulnerability of this region from the viewpoint of CREB activation. The rat brain had been subjected to 90-min focal ischemia followed by various periods of recirculation. Focal ischemia was induced by occlusion of the middle cerebral artery using the intraluminal suture method. CA1 pyramidal neurons in the sham animals showed definite immunoreactivity with anti-CREB antibody, which binds to both unphosphorylated and phosphorylated CREB, while reactivity with anti-phosphorylated CREB antibody was barely detectable in these neurons. In contrast, at 3.5 h of recirculation, a significant increase in the number of phosphorylated CREB-positive neurons was noted in the CA1 on both sides, and the increase continued until 48 h of recirculation with a tendency for gradual decline. At each period, the ischemic side showed a more marked increase in the number of immunoreactive cells as compared to the nonischemic side. Cresyl violet staining revealed CA1 pyramidal neurons to be maintained intact until 14 day of recirculation, at which time CREB phosphorylation has returned to the control level. Transient global ischemia is known to induce only mild CREB phosphorylation in the CA1 followed by a frank neuronal loss in this region. These data suggest that CREB phosphorylation can be persistently activated in CA1 neurons after focal ischemia and that this phenomenon may be closely associated with protection of these neurons. (C) 2000 Academic Press.
AB - Phosphorylation of the DNA-binding transcription factor, cyclic AMP response element binding protein (CREB), was immunohistochemically examined in rat brain hippocampal CA1 in order to examine the ischemic vulnerability of this region from the viewpoint of CREB activation. The rat brain had been subjected to 90-min focal ischemia followed by various periods of recirculation. Focal ischemia was induced by occlusion of the middle cerebral artery using the intraluminal suture method. CA1 pyramidal neurons in the sham animals showed definite immunoreactivity with anti-CREB antibody, which binds to both unphosphorylated and phosphorylated CREB, while reactivity with anti-phosphorylated CREB antibody was barely detectable in these neurons. In contrast, at 3.5 h of recirculation, a significant increase in the number of phosphorylated CREB-positive neurons was noted in the CA1 on both sides, and the increase continued until 48 h of recirculation with a tendency for gradual decline. At each period, the ischemic side showed a more marked increase in the number of immunoreactive cells as compared to the nonischemic side. Cresyl violet staining revealed CA1 pyramidal neurons to be maintained intact until 14 day of recirculation, at which time CREB phosphorylation has returned to the control level. Transient global ischemia is known to induce only mild CREB phosphorylation in the CA1 followed by a frank neuronal loss in this region. These data suggest that CREB phosphorylation can be persistently activated in CA1 neurons after focal ischemia and that this phenomenon may be closely associated with protection of these neurons. (C) 2000 Academic Press.
KW - Cerebral ischemia
KW - CREB
KW - Cyclic AMP response element binding protein
KW - Hippocampal CA1
KW - Neuroprotection
KW - Pyramidal neuron
KW - Recirculation
UR - http://www.scopus.com/inward/record.url?scp=0034098485&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034098485&partnerID=8YFLogxK
U2 - 10.1006/exnr.1999.7313
DO - 10.1006/exnr.1999.7313
M3 - Article
VL - 161
SP - 462
EP - 471
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 2
ER -