Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys

John D. Elsworth, T. Hajszán, Csaba Leranth, Robert H. Roth

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Schizophrenia patients, long-term abusers of phencyclidine (PCP), and monkeys treated with PCP all exhibit enduring cognitive deficits. Evidence indicates that loss of prefrontal cortex spine synapses results in cognitive dysfunction, suggesting the presence of synaptic pathology in the monkey PCP model; however, there is no direct evidence of such changes. In this study we use the monkey PCP model of schizophrenia to investigate at the ultrastructural level whether remodelling of dorsolateral prefrontal cortex (DLPFC) asymmetric spine synapses occurs following PCP. Subchronic PCP treatment resulted in a decrease in the number of asymmetric spine synapses, which was greater in layer II/III than layer V of DLPFC, compared to vehicle-treated controls. This decrease may contribute to PCP-induced cognitive dysfunction in the non-human primate model and perhaps in schizophrenia. Thus, the synapse loss in the PCP model provides a novel target for the development of potential treatments of cognitive dysfunction in this model and in schizophrenia.

Original languageEnglish
Pages (from-to)1411-1415
Number of pages5
JournalInternational Journal of Neuropsychopharmacology
Volume14
Issue number10
DOIs
Publication statusPublished - Nov 2011

Fingerprint

Phencyclidine
Prefrontal Cortex
Synapses
Haplorhini
Schizophrenia
Spine
Primates
Pathology
Therapeutics
Cognitive Dysfunction

Keywords

  • Asymmetric synapse
  • electron microscopy
  • phencyclidine
  • prefrontal cortex
  • schizophrenia

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys. / Elsworth, John D.; Hajszán, T.; Leranth, Csaba; Roth, Robert H.

In: International Journal of Neuropsychopharmacology, Vol. 14, No. 10, 11.2011, p. 1411-1415.

Research output: Contribution to journalArticle

@article{c9268d3b50e24c78b061ab18d396b77b,
title = "Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys",
abstract = "Schizophrenia patients, long-term abusers of phencyclidine (PCP), and monkeys treated with PCP all exhibit enduring cognitive deficits. Evidence indicates that loss of prefrontal cortex spine synapses results in cognitive dysfunction, suggesting the presence of synaptic pathology in the monkey PCP model; however, there is no direct evidence of such changes. In this study we use the monkey PCP model of schizophrenia to investigate at the ultrastructural level whether remodelling of dorsolateral prefrontal cortex (DLPFC) asymmetric spine synapses occurs following PCP. Subchronic PCP treatment resulted in a decrease in the number of asymmetric spine synapses, which was greater in layer II/III than layer V of DLPFC, compared to vehicle-treated controls. This decrease may contribute to PCP-induced cognitive dysfunction in the non-human primate model and perhaps in schizophrenia. Thus, the synapse loss in the PCP model provides a novel target for the development of potential treatments of cognitive dysfunction in this model and in schizophrenia.",
keywords = "Asymmetric synapse, electron microscopy, phencyclidine, prefrontal cortex, schizophrenia",
author = "Elsworth, {John D.} and T. Hajsz{\'a}n and Csaba Leranth and Roth, {Robert H.}",
year = "2011",
month = "11",
doi = "10.1017/S1461145711000939",
language = "English",
volume = "14",
pages = "1411--1415",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
publisher = "Cambridge University Press",
number = "10",

}

TY - JOUR

T1 - Loss of asymmetric spine synapses in dorsolateral prefrontal cortex of cognitively impaired phencyclidine-treated monkeys

AU - Elsworth, John D.

AU - Hajszán, T.

AU - Leranth, Csaba

AU - Roth, Robert H.

PY - 2011/11

Y1 - 2011/11

N2 - Schizophrenia patients, long-term abusers of phencyclidine (PCP), and monkeys treated with PCP all exhibit enduring cognitive deficits. Evidence indicates that loss of prefrontal cortex spine synapses results in cognitive dysfunction, suggesting the presence of synaptic pathology in the monkey PCP model; however, there is no direct evidence of such changes. In this study we use the monkey PCP model of schizophrenia to investigate at the ultrastructural level whether remodelling of dorsolateral prefrontal cortex (DLPFC) asymmetric spine synapses occurs following PCP. Subchronic PCP treatment resulted in a decrease in the number of asymmetric spine synapses, which was greater in layer II/III than layer V of DLPFC, compared to vehicle-treated controls. This decrease may contribute to PCP-induced cognitive dysfunction in the non-human primate model and perhaps in schizophrenia. Thus, the synapse loss in the PCP model provides a novel target for the development of potential treatments of cognitive dysfunction in this model and in schizophrenia.

AB - Schizophrenia patients, long-term abusers of phencyclidine (PCP), and monkeys treated with PCP all exhibit enduring cognitive deficits. Evidence indicates that loss of prefrontal cortex spine synapses results in cognitive dysfunction, suggesting the presence of synaptic pathology in the monkey PCP model; however, there is no direct evidence of such changes. In this study we use the monkey PCP model of schizophrenia to investigate at the ultrastructural level whether remodelling of dorsolateral prefrontal cortex (DLPFC) asymmetric spine synapses occurs following PCP. Subchronic PCP treatment resulted in a decrease in the number of asymmetric spine synapses, which was greater in layer II/III than layer V of DLPFC, compared to vehicle-treated controls. This decrease may contribute to PCP-induced cognitive dysfunction in the non-human primate model and perhaps in schizophrenia. Thus, the synapse loss in the PCP model provides a novel target for the development of potential treatments of cognitive dysfunction in this model and in schizophrenia.

KW - Asymmetric synapse

KW - electron microscopy

KW - phencyclidine

KW - prefrontal cortex

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=80054969925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054969925&partnerID=8YFLogxK

U2 - 10.1017/S1461145711000939

DO - 10.1017/S1461145711000939

M3 - Article

VL - 14

SP - 1411

EP - 1415

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

SN - 1461-1457

IS - 10

ER -