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.
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Bhavya
authors.initials: B
authors.lastname: Voleti
authors.forename: Tibor
authors.initials: T
authors.lastname: Hajszan
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rajkowska
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: Pawel
authors.initials: P
authors.lastname: Licznerski
authors.forename: Ashley
authors.initials: A
authors.lastname: Lepack
authors.forename: Mahesh S
authors.initials: MS
authors.lastname: Majik
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
authors.forename: Mounira
authors.initials: M
authors.lastname: Banasr
authors.forename: Hyeon
authors.initials: H
authors.lastname: Son
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002460:Cell Line; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology*; D050982:GATA1 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D046228:Microarray Analysis; D008854:Microscopy, Electron; D017397:Prefrontal Cortex / Q000473:pathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism / Q000473:pathology*; D016704:Synapsins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism
chemical_list: C488659:CALM2 protein, human; D002147:Calmodulin; D050982:GATA1 Transcription Factor; D016704:Synapsins; D014404:Tubulin; D020826:rab3A GTP-Binding Protein; D020695:rab4 GTP-Binding Proteins