Overexpression of human GATA-1 and GATA-2 interferes with spine formation and produces depressive behavior in rats

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...

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Bibliographic Details
Published in:PloS one 2014-10, Vol.9 (10), p.e109253-e109253
Main Authors: Choi, Miyeon, Wang, Sung Eun, Ko, Seung Yeon, Kang, Hyo Jung, Chae, Seung Yeun, Lee, Seung Hoon, Kim, Yong-Seok, Duman, Ronald S, Son, Hyeon
Format: Article
Language:English
Subjects:
Animal models
Animals
Antidepressants
Behavior
Behavior, Animal
Biochemistry
Biology and Life Sciences
Brain
Cells, Cultured
Cloning
Dendritic branching
Dendritic spines
Dendritic Spines - metabolism
Dendritic structure
Dentate gyrus
Deoxyribonucleic acid
Dependovirus - metabolism
Depression - metabolism
DNA
Embryos
Engineering
Fetuses
GATA-2 protein
GATA1 Transcription Factor - metabolism
GATA2 Transcription Factor - metabolism
Gene expression
Gene Expression Regulation
Genes
Green Fluorescent Proteins - metabolism
Hippocampus
Hippocampus - pathology
Human behavior
Humans
Laboratories
Learned helplessness
Male
Medicine
Mental depression
Molecular biology
Neurogenesis
Neurons
Neurosciences
Psychiatry
Rats
Rats, Sprague-Dawley
Rats, Transgenic
RNA, Small Interfering - metabolism
Rodents
Science
Stress
Synapses - metabolism
Synaptic density
Synaptic depression
Transcription factors
Transcription, Genetic
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0109253