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Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia

Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30–100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neuron...

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Autores principales: Pietersen, Charmaine Y., Mauney, Sarah A., Kim, Susie S., Lim, Maribel P., Rooney, Robert J., Goldstein, Jill M., Petryshen, Tracey L., Seidman, Larry J., Shenton, Martha E., McCarley, Robert W., Sonntag, Kai-C., Woo, Tsung-Ung W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Informa Healthcare 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196521/
https://www.ncbi.nlm.nih.gov/pubmed/24702465
http://dx.doi.org/10.3109/01677063.2014.882918
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author Pietersen, Charmaine Y.
Mauney, Sarah A.
Kim, Susie S.
Lim, Maribel P.
Rooney, Robert J.
Goldstein, Jill M.
Petryshen, Tracey L.
Seidman, Larry J.
Shenton, Martha E.
McCarley, Robert W.
Sonntag, Kai-C.
Woo, Tsung-Ung W.
author_facet Pietersen, Charmaine Y.
Mauney, Sarah A.
Kim, Susie S.
Lim, Maribel P.
Rooney, Robert J.
Goldstein, Jill M.
Petryshen, Tracey L.
Seidman, Larry J.
Shenton, Martha E.
McCarley, Robert W.
Sonntag, Kai-C.
Woo, Tsung-Ung W.
author_sort Pietersen, Charmaine Y.
collection PubMed
description Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30–100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann’s area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-β) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated.
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spelling pubmed-41965212014-10-27 Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia Pietersen, Charmaine Y. Mauney, Sarah A. Kim, Susie S. Lim, Maribel P. Rooney, Robert J. Goldstein, Jill M. Petryshen, Tracey L. Seidman, Larry J. Shenton, Martha E. McCarley, Robert W. Sonntag, Kai-C. Woo, Tsung-Ung W. J Neurogenet Original Research Articles Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30–100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann’s area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-β) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated. Informa Healthcare 2014-06 2014-04-10 /pmc/articles/PMC4196521/ /pubmed/24702465 http://dx.doi.org/10.3109/01677063.2014.882918 Text en © 2014 Informa Healthcare USA, Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.
spellingShingle Original Research Articles
Pietersen, Charmaine Y.
Mauney, Sarah A.
Kim, Susie S.
Lim, Maribel P.
Rooney, Robert J.
Goldstein, Jill M.
Petryshen, Tracey L.
Seidman, Larry J.
Shenton, Martha E.
McCarley, Robert W.
Sonntag, Kai-C.
Woo, Tsung-Ung W.
Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
title Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
title_full Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
title_fullStr Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
title_full_unstemmed Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
title_short Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
title_sort molecular profiles of pyramidal neurons in the superior temporal cortex in schizophrenia
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196521/
https://www.ncbi.nlm.nih.gov/pubmed/24702465
http://dx.doi.org/10.3109/01677063.2014.882918
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