Reduced density of cholinergic interneurons in the ventral striatum in Schizophrenia: An in situ hybridization study

Daphne J. Holt; Susan E. Bachus; Thomas M. Hyde; Michael Wittie; Mary M. Herman; Mark Vangel; Clifford B. Saper; Joel E. Kleinman

doi:10.1016/j.biopsych.2005.04.007

Reduced density of cholinergic interneurons in the ventral striatum in Schizophrenia: An in situ hybridization study

Daphne J. Holt, Susan E. Bachus, Thomas M. Hyde, Michael Wittie, Mary M. Herman, Mark Vangel, Clifford B. Saper, Joel E. Kleinman

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. Methods: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and β-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and β-actin mRNA expression levels were measured. Results: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of β-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. Conclusions: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.

Original language	English (US)
Pages (from-to)	408-416
Number of pages	9
Journal	Biological psychiatry
Volume	58
Issue number	5
DOIs	https://doi.org/10.1016/j.biopsych.2005.04.007
State	Published - Sep 1 2005
Externally published	Yes

Keywords

Basal ganglia
Cholinergic
In situ hybridization
Postmortem
Schizophrenia
Striatum

ASJC Scopus subject areas

Biological Psychiatry

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Reduced density of cholinergic interneurons in the ventral striatum in Schizophrenia : An in situ hybridization study. / Holt, Daphne J.; Bachus, Susan E.; Hyde, Thomas M.; Wittie, Michael; Herman, Mary M.; Vangel, Mark; Saper, Clifford B.; Kleinman, Joel E.

In: Biological psychiatry, Vol. 58, No. 5, 01.09.2005, p. 408-416.

Research output: Contribution to journal › Article › peer-review

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title = "Reduced density of cholinergic interneurons in the ventral striatum in Schizophrenia: An in situ hybridization study",

abstract = "Background: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. Methods: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and β-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and β-actin mRNA expression levels were measured. Results: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of β-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. Conclusions: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.",

keywords = "Basal ganglia, Cholinergic, In situ hybridization, Postmortem, Schizophrenia, Striatum",

author = "Holt, {Daphne J.} and Bachus, {Susan E.} and Hyde, {Thomas M.} and Michael Wittie and Herman, {Mary M.} and Mark Vangel and Saper, {Clifford B.} and Kleinman, {Joel E.}",

note = "Funding Information: DJH was supported by the Harvard-MIT Clinical Investigator Training Program, the Dupont-Warren Fellowship and the Jerome Lyle Rappaport Charitable Foundation. The authors thank Dr. Juraj Cervenak, Colleen Lynch, and Yuri Agrawal for excellent technical assistance and Drs. Oliver Freudenrich, Eden Evins, and Donald Goff for helpful comments on the manuscript. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.biopsych.2005.04.007",

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T2 - An in situ hybridization study

AU - Holt, Daphne J.

AU - Bachus, Susan E.

AU - Hyde, Thomas M.

AU - Wittie, Michael

AU - Herman, Mary M.

AU - Vangel, Mark

AU - Saper, Clifford B.

AU - Kleinman, Joel E.

N1 - Funding Information: DJH was supported by the Harvard-MIT Clinical Investigator Training Program, the Dupont-Warren Fellowship and the Jerome Lyle Rappaport Charitable Foundation. The authors thank Dr. Juraj Cervenak, Colleen Lynch, and Yuri Agrawal for excellent technical assistance and Drs. Oliver Freudenrich, Eden Evins, and Donald Goff for helpful comments on the manuscript. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2005/9/1

Y1 - 2005/9/1

N2 - Background: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. Methods: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and β-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and β-actin mRNA expression levels were measured. Results: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of β-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. Conclusions: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.

AB - Background: The role of the striatum in the pathophysiology of schizophrenia is not understood. In a previous postmortem study, we found a reduction in the density of striatal interneurons that stain immunohistochemically for choline acetyltransferase (ChAT) in schizophrenia. Methods: To determine whether this finding represents a specific alteration in ChAT gene expression, we used in situ hybridization to study the striatum of 11 control and 9 schizophrenic subjects with oligonucleotide probes complementary to human ChAT mRNA, preprosomatostatin (PPS) mRNA, and β-actin mRNA. Densities of ChAT mRNA-positive neurons, ChAT mRNA expression per neuron, PPS mRNA-positive neurons, and β-actin mRNA expression levels were measured. Results: There were no significant differences between the two groups in densities of PPS mRNA-positive neurons and levels of β-actin mRNA expression throughout the striatum, or in densities of ChAT mRNA-positive neurons in the caudate nucleus or putamen. However, in the ventral striatum, the mean density of ChAT mRNA-positive neurons was reduced to 26% of control levels in the schizophrenic group. Conclusions: There is a reduction in number or function of the cholinergic interneurons of the ventral striatum in schizophrenia.

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KW - In situ hybridization

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KW - Schizophrenia

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Reduced density of cholinergic interneurons in the ventral striatum in Schizophrenia: An in situ hybridization study

Abstract

Keywords

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