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Status |
Public on Apr 01, 2010 |
Title |
Transcriptional alterations in cycling neural stem cells underlying alcohol use disorders |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Ethanol inhibits the proliferation of neural stem cells in the fetal, adolescent, and adult brain. The consequences are cognitive deficits associated with fetal alcohol spectrum disorder and alcohol use disorder. We tested the hypothesis that ethanol affects progression through cell cycle checkpoints by differentially modifying transcriptional processes. Monolayer cultures of NS-5 neural stem cells were treated for 48 hr with the mitogenic agent FGF2 or the anti-mitogenic TGFβ1 in the absence or presence of ethanol. Cell cycle elongation was induced by a global down-regulation of genes involved in cell cycle progression, including the cyclin E system. Checkpoint regulation occurred downstream of p21 and Jun-oncogene signaling cascades. Thus, ethanol can affect cell cycle progression by altering transcript expression of strategic genes downstream of the G1/S checkpoint.
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Overall design |
NS5 neural stem cells were grown in Euromed Media supplemented with N2 and glutamine. Cells were plated on poly-ornathine and laminin in the presence of FGF2 (10 ng/ul) and EGF (10 ng/ul) for 24 hrs. Media was removed, cells were rinsed, and placed in growth factor free conditions for 4 hrs. NS5 cells were then exposed to one of four treatment for 48 hrs: FGF2 (10 ng/ul) only, FGF2 (10 ng/ul) and ethanol (400 mg/dl), TGF-beta1 (10 ng/ul) only, or TGF-beta1 (10 ng/ul) and ethanol (400 mg/dl). Total RNA was collected immediately following treatment.
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Contributor(s) |
Hicks SD, Middleton FA, Miller MW |
Citation(s) |
20626555, 23095216 |
Submission date |
Dec 11, 2009 |
Last update date |
Feb 11, 2019 |
Contact name |
Frank A Middleton |
E-mail(s) |
middletf@upstate.edu
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Phone |
315-464-7721
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Organization name |
SUNY Upstate Medical Univ
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Department |
Neuroscience and Physiology
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Street address |
505 Irving Avenue
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City |
Syracuse |
State/province |
NY |
ZIP/Postal code |
13210 |
Country |
USA |
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Platforms (1) |
GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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Samples (8)
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GSM484364 |
Ethanol and FGF2 treated replicate 2 |
GSM484365 |
Ethanol and FGF2 treated replicate 1 |
GSM484366 |
Ethanol and TGF-beta1 treated replicate 1 |
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Relations |
BioProject |
PRJNA122307 |