title: Overexpression of human GATA-1 and GATA-2 interferes with spine formation and produces depressive behavior in rats.
abstract: Functional consequences to which vertebrate GATA transcription factors contribute in the adult brain remain largely an open question. The present study examines how human GATA-1 and GATA-2 (hGATA-1 and hGATA-2) are linked to neuronal differentiation and depressive behaviors in rats. We investigated the effects of adeno-associated viral expression of hGATA-1 and hGATA-2 (AAV-hGATA1 and AAV-hGATA2) in the dentate gyrus (DG) of the dorsal hippocampus on dendrite branching and spine number. We also examined the influence of AAV-hGATA1 and AAV-hGATA2 infusions into the dorsal hippocampus on rodent behavior in models of depression. Viral expression of hGATA-1 and hGATA-2 cDNA in rat hippocampal neurons impaired dendritic outgrowth and spine formation. Moreover, viral-mediated expression of hGATA-1 and hGATA-2 in the dorsal hippocampus caused depressive-like deficits in the forced swim test and learned helplessness models of depression, and decreased the expression of several synapse-related genes as well as spine number in hippocampal neurons. Conversely, shRNA knockdown of GATA-2 increased synapse-related gene expression, spine number, and dendrite branching. The results demonstrate that hGATA-1 and hGATA-2 expression in hippocampus is sufficient to cause depressive like behaviors that are associated with reduction in spine synapse density and expression of synapse-related genes.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Miyeon
authors.initials: M
authors.lastname: Choi
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Wang
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Seung Yeon
authors.initials: SY
authors.lastname: Ko
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Seung Yeun
authors.initials: SY
authors.lastname: Chae
authors.affiliation: Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Psychiatry, Center for Genes and Behavior, Departments of Psychiatry, Neurobiology, and Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.
authors.forename: Hyeon
authors.initials: H
authors.lastname: Son
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D000229:Dependovirus / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013569:Synapses / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins