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Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder

Previous imaging and postmortem studies have reported a reduction in brain volume and a decrease in the size and density of neurons in the dorsolateral prefrontal cortex (dlPFC, area 9) of subjects with major depressive disorder (MDD).(1,2) These findings suggest that synapse number and function are...

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Autores principales: Kang, H.J., Voleti, B., Hajszan, T., Rajkowska, G., Stockmeier, C., Licznerski, P., Lepack, A., Majik, M.S., Jeong, L.S., Banasr, M., Son, H., Duman, R.S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491115/
https://www.ncbi.nlm.nih.gov/pubmed/22885997
http://dx.doi.org/10.1038/nm.2886
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author Kang, H.J.
Voleti, B.
Hajszan, T.
Rajkowska, G.
Stockmeier, C.
Licznerski, P.
Lepack, A.
Majik, M.S.
Jeong, L.S.
Banasr, M.
Son, H.
Duman, R.S.
author_facet Kang, H.J.
Voleti, B.
Hajszan, T.
Rajkowska, G.
Stockmeier, C.
Licznerski, P.
Lepack, A.
Majik, M.S.
Jeong, L.S.
Banasr, M.
Son, H.
Duman, R.S.
author_sort Kang, H.J.
collection PubMed
description Previous imaging and postmortem studies have reported a reduction in brain volume and a decrease in the size and density of neurons in the dorsolateral prefrontal cortex (dlPFC, area 9) of subjects with major depressive disorder (MDD).(1,2) These findings suggest that synapse number and function are decreased in dlPFC of depressed patients. However, there has been no direct evidence for synapse loss in MDD and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal decreased expression of synaptic function-related genes in dlPFC of MDD subjects and a corresponding reduction in the number of synapses. We also identify a transcriptional repressor that is increased in MDD, and that when expressed in PFC neurons is sufficient to decrease expression of synapse-related genes, cause loss of spines and dendrites, and produce depressive behavior in rodent models of depression.
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spelling pubmed-34911152013-03-01 Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder Kang, H.J. Voleti, B. Hajszan, T. Rajkowska, G. Stockmeier, C. Licznerski, P. Lepack, A. Majik, M.S. Jeong, L.S. Banasr, M. Son, H. Duman, R.S. Nat Med Article Previous imaging and postmortem studies have reported a reduction in brain volume and a decrease in the size and density of neurons in the dorsolateral prefrontal cortex (dlPFC, area 9) of subjects with major depressive disorder (MDD).(1,2) These findings suggest that synapse number and function are decreased in dlPFC of depressed patients. However, there has been no direct evidence for synapse loss in MDD and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal decreased expression of synaptic function-related genes in dlPFC of MDD subjects and a corresponding reduction in the number of synapses. We also identify a transcriptional repressor that is increased in MDD, and that when expressed in PFC neurons is sufficient to decrease expression of synapse-related genes, cause loss of spines and dendrites, and produce depressive behavior in rodent models of depression. 2012-09 /pmc/articles/PMC3491115/ /pubmed/22885997 http://dx.doi.org/10.1038/nm.2886 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Kang, H.J.
Voleti, B.
Hajszan, T.
Rajkowska, G.
Stockmeier, C.
Licznerski, P.
Lepack, A.
Majik, M.S.
Jeong, L.S.
Banasr, M.
Son, H.
Duman, R.S.
Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder
title Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder
title_full Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder
title_fullStr Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder
title_full_unstemmed Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder
title_short Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder
title_sort decreased expression of synapse-related genes and loss of synapses in major depressive disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491115/
https://www.ncbi.nlm.nih.gov/pubmed/22885997
http://dx.doi.org/10.1038/nm.2886
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