Overexpression of Human GATA-1 and GATA-2 Interferes with Spine Formation and Produces Depressive Behavior in Rats
- Title
- Overexpression of Human GATA-1 and GATA-2 Interferes with Spine Formation and Produces Depressive Behavior in Rats
- Author
- 김용석
- Keywords
- ANTIDEPRESSANT ACTIONS; DENDRITIC SPINES; DENDRITIC SPINES; PROMOTER; EXPRESSION; PLASTICITY; BRAIN; IDENTIFICATION; PLASTICITY; REGULATOR
- Issue Date
- 2014-10
- Publisher
- PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
- Citation
- PLOS ONE, 9권, 10호, 논문번호 e109253
- 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.
- URI
- https://doi.org/10.1371/journal.pone.0109253http://hdl.handle.net/20.500.11754/52818
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0109253; 10.1371/journal.pone.0109253
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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