Altered expression of 14-3-3 in the prefrontal cortex of subjects with schizophrenia

Frank A. Middleton, Lansha Peng, David A. Lewis, Pat Levitt, K. Mirnics

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Seven distinct 14-3-3 proteins are expressed in mammals. One of the 14-3-3 genes (eta) has been previously associated with decreased expression in the prefrontal cortex (PFC) of subjects with schizophrenia. DNA microarray analysis of the PFC of 10 subjects with schizophrenia and 10 matched controls indicated that the majority of 14-3-3 genes exhibited moderate to marked decreases in expression in schizophrenia, which were significant at the group level across all 10 comparisons (p <0.021). Selected changes in gene expression were further examined using in situ hybridization (ISH) in the same subject pairs as well as in four monkeys treated chronically with haloperidol and matched control animals. All analyses were performed blind to subject identity and diagnosis, or treatment. ISH analysis and multivariate analysis of covariance confirmed the significant decreases in expression of two 14-3-3 genes: beta -3119%, zeta -18.2%. Two other 14-3-3 genes exhibited more modest decreases in expression levels that were significant only in pairwise comparisons that did not factor in post-mortem interval or tissue storage time: gamma -11.9%, eta -15.4%. In the PFC of haloperidol-treated monkeys, there was no difference in 14-3-3 zeta expression, while 14-3-3 beta increased 28% (p <0.05) as a result of neuroleptic treatment. Our results suggest that decreased expression of selected 14-3-3 genes is a common feature of schizophrenia and that the 14-3-3 beta transcript may be unique among the 14-3-3 genes in its increase in response to haloperidol and decrease in the disease state.

Original languageEnglish
Pages (from-to)974-983
Number of pages10
JournalNeuropsychopharmacology
Volume30
Issue number5
DOIs
Publication statusPublished - May 2005

Fingerprint

Prefrontal Cortex
Schizophrenia
Haloperidol
Genes
Haplorhini
In Situ Hybridization
14-3-3 Proteins
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Antipsychotic Agents
Mammals
Multivariate Analysis
Gene Expression

Keywords

  • DNA microarray
  • Gene expression
  • Haloperidol
  • In situ hybridization
  • Prefrontal cortex
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology

Cite this

Altered expression of 14-3-3 in the prefrontal cortex of subjects with schizophrenia. / Middleton, Frank A.; Peng, Lansha; Lewis, David A.; Levitt, Pat; Mirnics, K.

In: Neuropsychopharmacology, Vol. 30, No. 5, 05.2005, p. 974-983.

Research output: Contribution to journalArticle

Middleton, Frank A. ; Peng, Lansha ; Lewis, David A. ; Levitt, Pat ; Mirnics, K. / Altered expression of 14-3-3 in the prefrontal cortex of subjects with schizophrenia. In: Neuropsychopharmacology. 2005 ; Vol. 30, No. 5. pp. 974-983.
@article{bd5fa3b7643f47e0b6ce6dc20f929331,
title = "Altered expression of 14-3-3 in the prefrontal cortex of subjects with schizophrenia",
abstract = "Seven distinct 14-3-3 proteins are expressed in mammals. One of the 14-3-3 genes (eta) has been previously associated with decreased expression in the prefrontal cortex (PFC) of subjects with schizophrenia. DNA microarray analysis of the PFC of 10 subjects with schizophrenia and 10 matched controls indicated that the majority of 14-3-3 genes exhibited moderate to marked decreases in expression in schizophrenia, which were significant at the group level across all 10 comparisons (p <0.021). Selected changes in gene expression were further examined using in situ hybridization (ISH) in the same subject pairs as well as in four monkeys treated chronically with haloperidol and matched control animals. All analyses were performed blind to subject identity and diagnosis, or treatment. ISH analysis and multivariate analysis of covariance confirmed the significant decreases in expression of two 14-3-3 genes: beta -3119{\%}, zeta -18.2{\%}. Two other 14-3-3 genes exhibited more modest decreases in expression levels that were significant only in pairwise comparisons that did not factor in post-mortem interval or tissue storage time: gamma -11.9{\%}, eta -15.4{\%}. In the PFC of haloperidol-treated monkeys, there was no difference in 14-3-3 zeta expression, while 14-3-3 beta increased 28{\%} (p <0.05) as a result of neuroleptic treatment. Our results suggest that decreased expression of selected 14-3-3 genes is a common feature of schizophrenia and that the 14-3-3 beta transcript may be unique among the 14-3-3 genes in its increase in response to haloperidol and decrease in the disease state.",
keywords = "DNA microarray, Gene expression, Haloperidol, In situ hybridization, Prefrontal cortex, Schizophrenia",
author = "Middleton, {Frank A.} and Lansha Peng and Lewis, {David A.} and Pat Levitt and K. Mirnics",
year = "2005",
month = "5",
doi = "10.1038/sj.npp.1300674",
language = "English",
volume = "30",
pages = "974--983",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Altered expression of 14-3-3 in the prefrontal cortex of subjects with schizophrenia

AU - Middleton, Frank A.

AU - Peng, Lansha

AU - Lewis, David A.

AU - Levitt, Pat

AU - Mirnics, K.

PY - 2005/5

Y1 - 2005/5

N2 - Seven distinct 14-3-3 proteins are expressed in mammals. One of the 14-3-3 genes (eta) has been previously associated with decreased expression in the prefrontal cortex (PFC) of subjects with schizophrenia. DNA microarray analysis of the PFC of 10 subjects with schizophrenia and 10 matched controls indicated that the majority of 14-3-3 genes exhibited moderate to marked decreases in expression in schizophrenia, which were significant at the group level across all 10 comparisons (p <0.021). Selected changes in gene expression were further examined using in situ hybridization (ISH) in the same subject pairs as well as in four monkeys treated chronically with haloperidol and matched control animals. All analyses were performed blind to subject identity and diagnosis, or treatment. ISH analysis and multivariate analysis of covariance confirmed the significant decreases in expression of two 14-3-3 genes: beta -3119%, zeta -18.2%. Two other 14-3-3 genes exhibited more modest decreases in expression levels that were significant only in pairwise comparisons that did not factor in post-mortem interval or tissue storage time: gamma -11.9%, eta -15.4%. In the PFC of haloperidol-treated monkeys, there was no difference in 14-3-3 zeta expression, while 14-3-3 beta increased 28% (p <0.05) as a result of neuroleptic treatment. Our results suggest that decreased expression of selected 14-3-3 genes is a common feature of schizophrenia and that the 14-3-3 beta transcript may be unique among the 14-3-3 genes in its increase in response to haloperidol and decrease in the disease state.

AB - Seven distinct 14-3-3 proteins are expressed in mammals. One of the 14-3-3 genes (eta) has been previously associated with decreased expression in the prefrontal cortex (PFC) of subjects with schizophrenia. DNA microarray analysis of the PFC of 10 subjects with schizophrenia and 10 matched controls indicated that the majority of 14-3-3 genes exhibited moderate to marked decreases in expression in schizophrenia, which were significant at the group level across all 10 comparisons (p <0.021). Selected changes in gene expression were further examined using in situ hybridization (ISH) in the same subject pairs as well as in four monkeys treated chronically with haloperidol and matched control animals. All analyses were performed blind to subject identity and diagnosis, or treatment. ISH analysis and multivariate analysis of covariance confirmed the significant decreases in expression of two 14-3-3 genes: beta -3119%, zeta -18.2%. Two other 14-3-3 genes exhibited more modest decreases in expression levels that were significant only in pairwise comparisons that did not factor in post-mortem interval or tissue storage time: gamma -11.9%, eta -15.4%. In the PFC of haloperidol-treated monkeys, there was no difference in 14-3-3 zeta expression, while 14-3-3 beta increased 28% (p <0.05) as a result of neuroleptic treatment. Our results suggest that decreased expression of selected 14-3-3 genes is a common feature of schizophrenia and that the 14-3-3 beta transcript may be unique among the 14-3-3 genes in its increase in response to haloperidol and decrease in the disease state.

KW - DNA microarray

KW - Gene expression

KW - Haloperidol

KW - In situ hybridization

KW - Prefrontal cortex

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=17644370621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17644370621&partnerID=8YFLogxK

U2 - 10.1038/sj.npp.1300674

DO - 10.1038/sj.npp.1300674

M3 - Article

VL - 30

SP - 974

EP - 983

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 5

ER -