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| Status |
Public on Apr 19, 2012 |
| Title |
MAPK Signaling Determines Anxiety in the Juvenile Mouse Brain but Depression-like Behavior in Adults |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In these mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as new valuable approach, allowing to discriminate between gene function in the adult and the developing postnatal brain.
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| Overall design |
Five male Braf-cko, six male homozygous Braf-flox littermates, six male heterozygous CamkII-Cre, and six male wildtype littermates were killed with CO2, the complete hippocampal tissue was prepared, and total RNA was extracted with the Trizol protocol. The integrity and quality of the RNA samples were analyzed with an RNA electrophoresis chip (RNA 6000 Nano Kit, Agilent, Boeblingen, Germany). RNA samples of high integrity and quality (RIN ≥ 7.5) were further processed with the TotalPrep RNA Amplification Kit (Ambion, Austin, TX, USA) and hybridized onto MouseWG-6 v1.1 Expression Bead-Chips (Illumina, San Diego, CA, USA) following manufacturer’s instructions. Data were analyzed using the software R (used packages: beadarray, limma, and vsn).
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| Contributor(s) |
Wefers B, Hitz C, Hölter SM, Trümbach D, Hansen J, Weber P, Pütz B, Deussing JM, Hrabe de Angelis M, Roenneberg T, Zheng F, Alzheimer C, Silva A, Wurst W, Kühn R |
| Citation(s) |
22529971 |
| Submission date |
Nov 10, 2011 |
| Last update date |
Jan 18, 2013 |
| Contact name |
Benedikt Wefers |
| Organization name |
Helmholtz Zentrum Muenchen
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| Department |
Institute of Developmental Genetics
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| Street address |
Ingolstaedter Landstr. 1
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| City |
Neuherberg/Munich |
| ZIP/Postal code |
85764 |
| Country |
Germany |
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| Platforms (1) |
| GPL6105 |
Illumina mouse-6 v1.1 expression beadchip |
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| Samples (36)
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| GSM831301 |
Braf-cko, biological replicate 1, technical replicate 1 |
| GSM831302 |
Braf-flox, biological replicate 1, technical replicate 1 |
| GSM831303 |
Braf-cko, biological replicate 2, technical replicate 1 |
| GSM831304 |
Braf-flox, biological replicate 2, technical replicate 1 |
| GSM831305 |
Braf-cko, biological replicate 3, technical replicate 1 |
| GSM831306 |
Braf-flox, biological replicate 3, technical replicate 1 |
| GSM831307 |
Braf-flox, biological replicate 4, technical replicate 1 |
| GSM831308 |
Braf-cko, biological replicate 4, technical replicate 1 |
| GSM831309 |
Braf-flox, biological replicate 5, technical replicate 1 |
| GSM831310 |
Braf-cko, biological replicate 5, technical replicate 1 |
| GSM831311 |
Braf-flox, biological replicate 6, technical replicate 1 |
| GSM831312 |
Braf-cko, biological replicate 1, technical replicate 2 |
| GSM831313 |
CamkII-Cre, biological replicate 1, technical replicate 1 |
| GSM831314 |
CamkII-wt, biological replicate 1, technical replicate 1 |
| GSM831315 |
CamkII-Cre, biological replicate 2, technical replicate 1 |
| GSM831316 |
CamkII-wt, biological replicate 2, technical replicate 1 |
| GSM831317 |
CamkII-Cre, biological replicate 3, technical replicate 1 |
| GSM831318 |
CamkII-wt, biological replicate 3, technical replicate 1 |
| GSM831319 |
CamkII-Cre, biological replicate 4, technical replicate 1 |
| GSM831320 |
CamkII-wt, biological replicate 4, technical replicate 1 |
| GSM831321 |
CamkII-Cre, biological replicate 5, technical replicate 1 |
| GSM831322 |
CamkII-wt, biological replicate 5, technical replicate 1 |
| GSM831323 |
CamkII-Cre, biological replicate 6, technical replicate 1 |
| GSM831324 |
CamkII-wt, biological replicate 6, technical replicate 1 |
| GSM831325 |
CamkII-Cre, biological replicate 1, technical replicate 2 |
| GSM831326 |
CamkII-wt, biological replicate 1, technical replicate 2 |
| GSM831327 |
CamkII-Cre, biological replicate 2, technical replicate 2 |
| GSM831328 |
CamkII-wt, biological replicate 2, technical replicate 2 |
| GSM831329 |
CamkII-Cre, biological replicate 3, technical replicate 2 |
| GSM831330 |
CamkII-wt, biological replicate 3, technical replicate 2 |
| GSM831331 |
CamkII-Cre, biological replicate 4, technical replicate 2 |
| GSM831332 |
CamkII-wt, biological replicate 4, technical replicate 2 |
| GSM831333 |
CamkII-Cre, biological replicate 5, technical replicate 2 |
| GSM831334 |
CamkII-wt, biological replicate 5, technical replicate 2 |
| GSM831335 |
CamkII-Cre, biological replicate 6, technical replicate 2 |
| GSM831336 |
CamkII-wt, biological replicate 6, technical replicate 2 |
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| Relations |
| BioProject |
PRJNA148495 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33618_RAW.tar |
5.2 Mb |
(http)(custom) |
TAR |
| GSE33618_non-normalized.txt.gz |
11.3 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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