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| Status |
Public on Jul 22, 2009 |
| Title |
Involvement of the brain renin-angiotensin system in the effects of maternal separation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The postnatal development of the mouse is characterized by a stress hyporesponsive period (SHRP), where basal corticosterone levels are low and responsiveness to mild stressors is reduced. Maternal separation is able to disrupt the SHRP and is widely used to model early trauma. In this study we aimed at identifying of brain systems involved in acute and possible long-term effects of maternal separation. We conducted a microarray-based gene expression analysis in the hypothalamic paraventricular nucleus after maternal separation, which revealed 52 differently regulated genes compared to undisturbed controls, among them are 37 up-regulated and 15 down-regulated genes. One of the prominently unregulated genes, angiotensinogen, was validated using a in-situ hybridization. Angiotensinogen is the precursor of angiotensin II the main effector of the brain renin-angiotensin system (RAS), which is known to be involved in stress system modulation in adult animals. Using the selective angiotensin type I receptor (AT(1)) antagonist candesartan we found strong effects on CRH and GR mRNA expression in the brain and ACTH release following maternal separation. AT(1) receptor blockade appears to enhance central effects of maternal separation in the neonate, suggesting a suppressing function of brain RAS during the SHRP. Taken together, our results illustrate the molecular adaptations that occur in the paraventricular nucleus following maternal separation and identify signaling cascades, that control stress system activity in the neonate.
Keywords: phenotype
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| Overall design |
Litters were randomly assigned to either a maternally non-separated or 24 hour maternally separated condition. At the time of testing, all pups from a litter were sacrificed immediately by decapitation.
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| Contributor(s) |
Liebl C, Panhuysen M, Pütz B, Trümbach D, Deussing J, Wurst W, Müller MB, Schmidt MV |
| Citation(s) |
19506703 |
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| Submission date |
Feb 03, 2009 |
| Last update date |
Mar 20, 2012 |
| Contact name |
Dietrich Trümbach |
| E-mail(s) |
dietrich.truembach@helmholtz-muenchen.de
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| Organization name |
German Research Center for Environmental Health
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| Department |
Institute for Developmental Genetics
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| Street address |
Ingolstädter Landstraße 1
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| City |
München-Neuherberg |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (10)
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| GSM366775 |
non-separated animals PVN, technical replicate 1 |
| GSM366776 |
non-separated animals PVN, technical replicate 2 |
| GSM366777 |
non-separated animals PVN, technical replicate 3 |
| GSM366778 |
non-separated animals PVN, technical replicate 4 |
| GSM366779 |
non-separated animals PVN, technical replicate 5 |
| GSM366780 |
separated animals PVN, technical replicate 1 |
| GSM366781 |
separated animals PVN, technical replicate 2 |
| GSM366782 |
separated animals PVN, technical replicate 3 |
| GSM366783 |
separated animals PVN, technical replicate 4 |
| GSM366784 |
separated animals PVN, technical replicate 5 |
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| Relations |
| BioProject |
PRJNA111675 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE14687_RAW.tar |
18.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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