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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
Authors
Kang H.J.Voleti B.Hajszan T.Rajkowska G.Stockmeier C.A.Licznerski P.Lepack A.Majik M.S.Jeong L.S.Banasr M.Son H.Duman R.S.
Ewha Authors
정낙신
Issue Date
2012
Journal Title
Nature Medicine
ISSN
1078-8956JCR Link
Citation
vol. 18, no. 9, pp. 1413 - 1417
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Previous imaging and postmortem studies have reported a lower brain volume and a smaller size and density of neurons in the dorsolateral prefrontal cortex (dlPFC) of subjects with major depressive disorder (MDD). These findings suggest that synapse number and function are decreased in the dlPFC of patients with MDD. However, there has been no direct evidence reported 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 lower expression of synaptic-function-related genes (CALM2, SYN1, RAB3A, RAB4B and TUBB4) in the dlPFC of subjects with MDD and a corresponding lower number of synapses. We also identify a transcriptional repressor, GATA1, expression of which is higher in MDD and that, when expressed in PFC neurons, is sufficient to decrease the expression of synapse-related genes, cause loss of dendritic spines and dendrites, and produce depressive behavior in rat models of depression. © 2012 Nature America, Inc. All rights reserved.
DOI
10.1038/nm.2886
Appears in Collections:
약학대학 > 약학과 > Journal papers
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