Overexpression of Human GATA-1 and GATA-2 Interferes with Spine Formation and Produces Depressive Behavior in Ratsopen access
- 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
- Issue Date
- Oct-2014
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.9, no.10, pp.1 - 10
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 9
- Number
- 10
- Start Page
- 1
- End Page
- 10
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/159027
- DOI
- 10.1371/journal.pone.0109253
- ISSN
- 1932-6203
- 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 synapserelated genes.
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