Postnatal phencyclidine administration selectively reduces adult cortical parvalbumin-containing interneurons

Cheng Z. Wang, San F. Yang, Yan Xia, Kenneth M. Johnson

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Transient postnatal NMDA receptor blockade by phencyclidine (PCP), ketamine, or MK-801 induces developmental neuroapoptosis and adult behavioral deficits, which resemble abnormal human behaviors typically present in schizophrenia. This study tested the hypothesis that PCP-induced developmental apoptosis causes a specific deficit of GABAergic interneurons containing parvalbumin (PV), calretinin (CR), or calbindin (CB). Young adult (PND56) rats that were given a single dose of PCP (10 mg/kg) on PND7 exhibited no densitometric change of either CR or CB neurons in any brain region studied, but demonstrated a selective deficit of PV-containing neurons in the superficial layers (II-IV) of the primary somatosensory (S1), motor (M), and retrosplenial cortices, but not in the striatum (CPu) or hippocampus. Further, CR and CB neurons, which were expressed at the time of PCP administration, showed no colocalization with cellular markers of apoptosis (terminal dUTP nick-end labeling (TUNEL) of broken DNA or cleaved caspase-3), indicating that CR- and CB-containing neurons were protected from the toxic effect of PCP and survived into adulthood. This suggests that the deletion of PV neurons occurred during development, but cleaved caspase-3 showed no colocalization with BrdU, a specific marker of S-phase proliferation. These data suggest that the loss of PV-containing neurons was not due to an effect of PCP on proliferating neurons, but rather an effect on post-mitotic neurons. The developmental dependence and neuronal specificity of this effect of PCP provides further evidence that this model may be valuable in exploring the pathophysiology of schizophrenia.

Original languageEnglish (US)
Pages (from-to)2442-2455
Number of pages14
JournalNeuropsychopharmacology
Volume33
Issue number10
DOIs
StatePublished - Sep 2008

Fingerprint

Parvalbumins
Phencyclidine
Interneurons
Calbindin 2
Neurons
Calbindins
Caspase 3
Schizophrenia
Apoptosis
Dizocilpine Maleate
Poisons
Ketamine
Bromodeoxyuridine
N-Methyl-D-Aspartate Receptors
S Phase
Young Adult
Hippocampus
DNA
Brain

Keywords

  • N-methyl-D-aspartate receptor
  • Neuroapoptosis
  • Neurogenesis
  • Parvalbumin
  • Phencyclidine
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Postnatal phencyclidine administration selectively reduces adult cortical parvalbumin-containing interneurons. / Wang, Cheng Z.; Yang, San F.; Xia, Yan; Johnson, Kenneth M.

In: Neuropsychopharmacology, Vol. 33, No. 10, 09.2008, p. 2442-2455.

Research output: Contribution to journalArticle

Wang, Cheng Z. ; Yang, San F. ; Xia, Yan ; Johnson, Kenneth M. / Postnatal phencyclidine administration selectively reduces adult cortical parvalbumin-containing interneurons. In: Neuropsychopharmacology. 2008 ; Vol. 33, No. 10. pp. 2442-2455.
@article{69cbb0b50eee49efa42af1abd24b26fd,
title = "Postnatal phencyclidine administration selectively reduces adult cortical parvalbumin-containing interneurons",
abstract = "Transient postnatal NMDA receptor blockade by phencyclidine (PCP), ketamine, or MK-801 induces developmental neuroapoptosis and adult behavioral deficits, which resemble abnormal human behaviors typically present in schizophrenia. This study tested the hypothesis that PCP-induced developmental apoptosis causes a specific deficit of GABAergic interneurons containing parvalbumin (PV), calretinin (CR), or calbindin (CB). Young adult (PND56) rats that were given a single dose of PCP (10 mg/kg) on PND7 exhibited no densitometric change of either CR or CB neurons in any brain region studied, but demonstrated a selective deficit of PV-containing neurons in the superficial layers (II-IV) of the primary somatosensory (S1), motor (M), and retrosplenial cortices, but not in the striatum (CPu) or hippocampus. Further, CR and CB neurons, which were expressed at the time of PCP administration, showed no colocalization with cellular markers of apoptosis (terminal dUTP nick-end labeling (TUNEL) of broken DNA or cleaved caspase-3), indicating that CR- and CB-containing neurons were protected from the toxic effect of PCP and survived into adulthood. This suggests that the deletion of PV neurons occurred during development, but cleaved caspase-3 showed no colocalization with BrdU, a specific marker of S-phase proliferation. These data suggest that the loss of PV-containing neurons was not due to an effect of PCP on proliferating neurons, but rather an effect on post-mitotic neurons. The developmental dependence and neuronal specificity of this effect of PCP provides further evidence that this model may be valuable in exploring the pathophysiology of schizophrenia.",
keywords = "N-methyl-D-aspartate receptor, Neuroapoptosis, Neurogenesis, Parvalbumin, Phencyclidine, Schizophrenia",
author = "Wang, {Cheng Z.} and Yang, {San F.} and Yan Xia and Johnson, {Kenneth M.}",
year = "2008",
month = "9",
doi = "10.1038/sj.npp.1301647",
language = "English (US)",
volume = "33",
pages = "2442--2455",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Postnatal phencyclidine administration selectively reduces adult cortical parvalbumin-containing interneurons

AU - Wang, Cheng Z.

AU - Yang, San F.

AU - Xia, Yan

AU - Johnson, Kenneth M.

PY - 2008/9

Y1 - 2008/9

N2 - Transient postnatal NMDA receptor blockade by phencyclidine (PCP), ketamine, or MK-801 induces developmental neuroapoptosis and adult behavioral deficits, which resemble abnormal human behaviors typically present in schizophrenia. This study tested the hypothesis that PCP-induced developmental apoptosis causes a specific deficit of GABAergic interneurons containing parvalbumin (PV), calretinin (CR), or calbindin (CB). Young adult (PND56) rats that were given a single dose of PCP (10 mg/kg) on PND7 exhibited no densitometric change of either CR or CB neurons in any brain region studied, but demonstrated a selective deficit of PV-containing neurons in the superficial layers (II-IV) of the primary somatosensory (S1), motor (M), and retrosplenial cortices, but not in the striatum (CPu) or hippocampus. Further, CR and CB neurons, which were expressed at the time of PCP administration, showed no colocalization with cellular markers of apoptosis (terminal dUTP nick-end labeling (TUNEL) of broken DNA or cleaved caspase-3), indicating that CR- and CB-containing neurons were protected from the toxic effect of PCP and survived into adulthood. This suggests that the deletion of PV neurons occurred during development, but cleaved caspase-3 showed no colocalization with BrdU, a specific marker of S-phase proliferation. These data suggest that the loss of PV-containing neurons was not due to an effect of PCP on proliferating neurons, but rather an effect on post-mitotic neurons. The developmental dependence and neuronal specificity of this effect of PCP provides further evidence that this model may be valuable in exploring the pathophysiology of schizophrenia.

AB - Transient postnatal NMDA receptor blockade by phencyclidine (PCP), ketamine, or MK-801 induces developmental neuroapoptosis and adult behavioral deficits, which resemble abnormal human behaviors typically present in schizophrenia. This study tested the hypothesis that PCP-induced developmental apoptosis causes a specific deficit of GABAergic interneurons containing parvalbumin (PV), calretinin (CR), or calbindin (CB). Young adult (PND56) rats that were given a single dose of PCP (10 mg/kg) on PND7 exhibited no densitometric change of either CR or CB neurons in any brain region studied, but demonstrated a selective deficit of PV-containing neurons in the superficial layers (II-IV) of the primary somatosensory (S1), motor (M), and retrosplenial cortices, but not in the striatum (CPu) or hippocampus. Further, CR and CB neurons, which were expressed at the time of PCP administration, showed no colocalization with cellular markers of apoptosis (terminal dUTP nick-end labeling (TUNEL) of broken DNA or cleaved caspase-3), indicating that CR- and CB-containing neurons were protected from the toxic effect of PCP and survived into adulthood. This suggests that the deletion of PV neurons occurred during development, but cleaved caspase-3 showed no colocalization with BrdU, a specific marker of S-phase proliferation. These data suggest that the loss of PV-containing neurons was not due to an effect of PCP on proliferating neurons, but rather an effect on post-mitotic neurons. The developmental dependence and neuronal specificity of this effect of PCP provides further evidence that this model may be valuable in exploring the pathophysiology of schizophrenia.

KW - N-methyl-D-aspartate receptor

KW - Neuroapoptosis

KW - Neurogenesis

KW - Parvalbumin

KW - Phencyclidine

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=49549088180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49549088180&partnerID=8YFLogxK

U2 - 10.1038/sj.npp.1301647

DO - 10.1038/sj.npp.1301647

M3 - Article

C2 - 18059437

AN - SCOPUS:49549088180

VL - 33

SP - 2442

EP - 2455

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 10

ER -