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| Status |
Public on Nov 18, 2016 |
| Title |
Transcriptional Response of Male MutaTMMouse Hippocampus to Benzo[a]pyrene (BaP; CAS no. 50-32-8, now also known as benzo[pqr]tetraphene) Exposure |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Benzo[a]pyrene (BaP) is a genotoxic carcinogen and a neurotoxicant. The neurotoxicity of BaP is proposed to arise from either genotoxicity leading to neuronal cell death, or perturbed expression of N-methyl-D-aspartate receptor (NMDAR) subunits. To explore these hypotheses, we profiled hippocampal gene expression of adult male MutaTMMouse administered 1, 35, or 70 mg BaP/kg bw per day by oral gavage for three days, by RNA-Sequencing (RNA-Seq), DNA microarrays, and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) 24 hr post-exposure. RNA-Seq revealed altered expression of zero, 260, and 219 genes (p-value < 0.05, fold-change ≥ ± 1.5) following exposure to the low, medium, and high doses, respectively; 54 genes were confirmed using microarrays.
Microarray and RT-PCR analysis showed increased expression of NMDAR subunits Grina and Grin2a. In contrast, no effects on classical BaP targets, including xenobiotic metabolism and DNA-damage response genes, were found, despite comparable BaP-DNA adduct levels in the cerebellum to those detected in the lung and liver in previous studies. Meta-analysis revealed that BaP-induced transcriptional profiles most closely match those from the hippocampus of transgenic mice that share neurotoxicity observed in BaP-exposed mice (i.e., defects in learning). Overall, our results support that BaP-induced neurotoxicity is more likely to be a consequence of NMDAR perturbation than of genotoxicity, and identify other important genes potentially mediating this adverse outcome.
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| Overall design |
Four (N=4) biological replicates were analyzed for control and BaP-treated (70 mg/kg bw per day, for 3 days) 24 h after the last treatment.
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| Contributor(s) |
Chepelev NL, Long AS, Bowers WJ, Gagné R, Williams A, Kuo B, Phillips DH, Arlt VM, White PA, Yauk CL |
| Citation(s) |
27195522 |
| Submission date |
Nov 19, 2015 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Nikolai L Chepelev |
| E-mail(s) |
nikolai.chepelev@gmail.com
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| Phone |
6138985388
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| Organization name |
Health Canada
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| Department |
Environmental Health Science and Research Bureau
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| Lab |
Genomics Laboratory
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| Street address |
50 Colombine Driveway
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| City |
Ottawa |
| State/province |
Ontario |
| ZIP/Postal code |
K1A0K9 |
| Country |
Canada |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA302798 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE75206_RAW.tar |
49.2 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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