Decreased expression of synapse-related genes and loss of synapses in major depressive disorder

Hyo Jung Kang; Bhavya Voleti; Tibor Hajszan; Grazyna Rajkowska; Craig A. Stockmeier; Pawel Licznerski; Ashley Lepack; Mahesh S. Majik; Lak Shin Jeong; Mounira Banasr; Hyeon Son; Ronald S. Duman

doi:10.1038/nm.2886

Decreased expression of synapse-related genes and loss of synapses in major depressive disorder

Hyo Jung Kang, Bhavya Voleti, Tibor Hajszan, Grazyna Rajkowska, Craig A. Stockmeier, Pawel Licznerski, Ashley Lepack, Mahesh S. Majik, Lak Shin Jeong, Mounira Banasr, Hyeon Son, Ronald S. Duman

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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.

Original language	English
Pages (from-to)	1413-1417
Number of pages	5
Journal	Nature Medicine
Volume	18
Issue number	9
DOIs	https://doi.org/10.1038/nm.2886
State	Published - Sep 2012
Externally published	Yes

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title = "Decreased expression of synapse-related genes and loss of synapses in major depressive disorder",

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.",

author = "Kang, {Hyo Jung} and Bhavya Voleti and Tibor Hajszan and Grazyna Rajkowska and Stockmeier, {Craig A.} and Pawel Licznerski and Ashley Lepack and Majik, {Mahesh S.} and Jeong, {Lak Shin} and Mounira Banasr and Hyeon Son and Duman, {Ronald S.}",

note = "Funding Information: This work is supported by US Public Health Service grants MH45481 (R.S.D.), 2 P01 MH25642 (R.S.D.), MH67996 (C.A.S.) and P20 RR17701 (C.A.S.), the Connecticut Mental Health Center (R.S.D.) and a National Research Foundation of Korea grant (NRF, 2011-0028317; H.S.). We acknowledge the invaluable contributions made by the families consenting to donate brain tissue and be interviewed. We also thank the",

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AU - Voleti, Bhavya

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AU - Stockmeier, Craig A.

AU - Licznerski, Pawel

AU - Lepack, Ashley

AU - Majik, Mahesh S.

AU - Jeong, Lak Shin

AU - Banasr, Mounira

AU - Son, Hyeon

AU - Duman, Ronald S.

N1 - Funding Information: This work is supported by US Public Health Service grants MH45481 (R.S.D.), 2 P01 MH25642 (R.S.D.), MH67996 (C.A.S.) and P20 RR17701 (C.A.S.), the Connecticut Mental Health Center (R.S.D.) and a National Research Foundation of Korea grant (NRF, 2011-0028317; H.S.). We acknowledge the invaluable contributions made by the families consenting to donate brain tissue and be interviewed. We also thank the

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Decreased expression of synapse-related genes and loss of synapses in major depressive disorder

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