Abstract
Phencyclidine and other N-methyl-D-aspartate receptor antagonists are toxic to pyramidal neurons in the posterior cingulate/retrosplenial cortex of rat brain. Previous studies have shown induction of heat shock protein 70 in affected neurons. In this study, expression of haem oxygenase-1, a heat shock protein induced by oxidative stress, was examined in rat forebrain after administration of a single intraperitoneal dose of phencyclidine (50 mg/kg). Northern and Western blot analyses of brain tissue extracts from phencyclidine-treated rats revealed a marked induction of haem oxygenase-1 mRNA and protein, respectively. Immunohistochemistry studies revealed that phencyclidine increased haem oxygenase-1 immunoreactivity primarily in posterior cingulate/retrosplenial, piriform and entorhinal cortices, striatum and hippocampus. Haem oxygenase-1 protein was induced in non-neuronal cells, mainly astrocytes. Some microglia expressing haem oxygenase-1 protein were also found in the posterior cingulate/retrosplenial cortex. Haem oxygenase-1 immunoreactive astrocytes and microglia were present in close proximity to the heat shock protein 70-positive neurons in the posterior cingulate/retrosplenial cortex following phencyclidine. Pretreatment of rats with 1,3-dimethylthiourea, an antioxidant, significantly reduced haem oxygenase-1 protein induction by phencyclidine. Thus, induction of haem oxygenase-1 in glia by phencyclidine appears to be mediated mostly by oxidative stress. Experiments with the amino cupric silver stain for neuronal degeneration revealed phencyclidine-induced neurotoxicity in the posterior cingulate/retrosplenial cortex. The number of affected neurons was significantly reduced after 1,3-dimethylthiourea pretreatment. This suggests that the neurotoxicity of N-methyl-D-aspartate antagonists is due in part to the oxidative stress and may be amenable to therapeutic interventions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3840-3852 |
| Number of pages | 13 |
| Journal | European Journal of Neuroscience |
| Volume | 10 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1998 |
| Externally published | Yes |
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Keywords
- Dopamine
- Haem oxygenase
- Heat shock proteins
- Neurodegeneration
- NMDA receptor antagonists
- Oxidative stress
- Schizophrenia
- Stress proteins
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Acute phencyclidine neurotoxicity in rat forebrain : Induction of haem oxygenase-1 and attenuation by the antioxidant dimethylthiourea. / Rajdev, Sunita; Fix, Andrew S.; Sharp, Frank R.
In: European Journal of Neuroscience, Vol. 10, No. 12, 12.1998, p. 3840-3852.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acute phencyclidine neurotoxicity in rat forebrain
T2 - Induction of haem oxygenase-1 and attenuation by the antioxidant dimethylthiourea
AU - Rajdev, Sunita
AU - Fix, Andrew S.
AU - Sharp, Frank R
PY - 1998/12
Y1 - 1998/12
N2 - Phencyclidine and other N-methyl-D-aspartate receptor antagonists are toxic to pyramidal neurons in the posterior cingulate/retrosplenial cortex of rat brain. Previous studies have shown induction of heat shock protein 70 in affected neurons. In this study, expression of haem oxygenase-1, a heat shock protein induced by oxidative stress, was examined in rat forebrain after administration of a single intraperitoneal dose of phencyclidine (50 mg/kg). Northern and Western blot analyses of brain tissue extracts from phencyclidine-treated rats revealed a marked induction of haem oxygenase-1 mRNA and protein, respectively. Immunohistochemistry studies revealed that phencyclidine increased haem oxygenase-1 immunoreactivity primarily in posterior cingulate/retrosplenial, piriform and entorhinal cortices, striatum and hippocampus. Haem oxygenase-1 protein was induced in non-neuronal cells, mainly astrocytes. Some microglia expressing haem oxygenase-1 protein were also found in the posterior cingulate/retrosplenial cortex. Haem oxygenase-1 immunoreactive astrocytes and microglia were present in close proximity to the heat shock protein 70-positive neurons in the posterior cingulate/retrosplenial cortex following phencyclidine. Pretreatment of rats with 1,3-dimethylthiourea, an antioxidant, significantly reduced haem oxygenase-1 protein induction by phencyclidine. Thus, induction of haem oxygenase-1 in glia by phencyclidine appears to be mediated mostly by oxidative stress. Experiments with the amino cupric silver stain for neuronal degeneration revealed phencyclidine-induced neurotoxicity in the posterior cingulate/retrosplenial cortex. The number of affected neurons was significantly reduced after 1,3-dimethylthiourea pretreatment. This suggests that the neurotoxicity of N-methyl-D-aspartate antagonists is due in part to the oxidative stress and may be amenable to therapeutic interventions.
AB - Phencyclidine and other N-methyl-D-aspartate receptor antagonists are toxic to pyramidal neurons in the posterior cingulate/retrosplenial cortex of rat brain. Previous studies have shown induction of heat shock protein 70 in affected neurons. In this study, expression of haem oxygenase-1, a heat shock protein induced by oxidative stress, was examined in rat forebrain after administration of a single intraperitoneal dose of phencyclidine (50 mg/kg). Northern and Western blot analyses of brain tissue extracts from phencyclidine-treated rats revealed a marked induction of haem oxygenase-1 mRNA and protein, respectively. Immunohistochemistry studies revealed that phencyclidine increased haem oxygenase-1 immunoreactivity primarily in posterior cingulate/retrosplenial, piriform and entorhinal cortices, striatum and hippocampus. Haem oxygenase-1 protein was induced in non-neuronal cells, mainly astrocytes. Some microglia expressing haem oxygenase-1 protein were also found in the posterior cingulate/retrosplenial cortex. Haem oxygenase-1 immunoreactive astrocytes and microglia were present in close proximity to the heat shock protein 70-positive neurons in the posterior cingulate/retrosplenial cortex following phencyclidine. Pretreatment of rats with 1,3-dimethylthiourea, an antioxidant, significantly reduced haem oxygenase-1 protein induction by phencyclidine. Thus, induction of haem oxygenase-1 in glia by phencyclidine appears to be mediated mostly by oxidative stress. Experiments with the amino cupric silver stain for neuronal degeneration revealed phencyclidine-induced neurotoxicity in the posterior cingulate/retrosplenial cortex. The number of affected neurons was significantly reduced after 1,3-dimethylthiourea pretreatment. This suggests that the neurotoxicity of N-methyl-D-aspartate antagonists is due in part to the oxidative stress and may be amenable to therapeutic interventions.
KW - Dopamine
KW - Haem oxygenase
KW - Heat shock proteins
KW - Neurodegeneration
KW - NMDA receptor antagonists
KW - Oxidative stress
KW - Schizophrenia
KW - Stress proteins
UR - http://www.scopus.com/inward/record.url?scp=0032464569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032464569&partnerID=8YFLogxK
U2 - 10.1046/j.1460-9568.1998.00392.x
DO - 10.1046/j.1460-9568.1998.00392.x
M3 - Article
C2 - 9875361
AN - SCOPUS:0032464569
VL - 10
SP - 3840
EP - 3852
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 12
ER -