MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults.
MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3329550?pdf=render |
| _version_ | 1819229020107046912 |
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| author | Benedikt Wefers Christiane Hitz Sabine M Hölter Dietrich Trümbach Jens Hansen Peter Weber Benno Pütz Jan M Deussing Martin Hrabé de Angelis Till Roenneberg Fang Zheng Christian Alzheimer Alcino Silva Wolfgang Wurst Ralf Kühn |
| author_facet | Benedikt Wefers Christiane Hitz Sabine M Hölter Dietrich Trümbach Jens Hansen Peter Weber Benno Pütz Jan M Deussing Martin Hrabé de Angelis Till Roenneberg Fang Zheng Christian Alzheimer Alcino Silva Wolfgang Wurst Ralf Kühn |
| author_sort | Benedikt Wefers |
| collection | DOAJ |
| description | MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, 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 inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive 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 a new valuable approach, allowing it to discriminate between gene function in the adult and the developing postnatal brain. |
| first_indexed | 2024-12-23T11:06:32Z |
| format | Article |
| id | doaj.art-fe31fe8bc67246bb8fd076f8b7b1270c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T11:06:32Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fe31fe8bc67246bb8fd076f8b7b1270c2022-12-21T17:49:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3503510.1371/journal.pone.0035035MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults.Benedikt WefersChristiane HitzSabine M HölterDietrich TrümbachJens HansenPeter WeberBenno PützJan M DeussingMartin Hrabé de AngelisTill RoennebergFang ZhengChristian AlzheimerAlcino SilvaWolfgang WurstRalf KühnMAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, 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 inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive 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 a new valuable approach, allowing it to discriminate between gene function in the adult and the developing postnatal brain.http://europepmc.org/articles/PMC3329550?pdf=render |
| spellingShingle | Benedikt Wefers Christiane Hitz Sabine M Hölter Dietrich Trümbach Jens Hansen Peter Weber Benno Pütz Jan M Deussing Martin Hrabé de Angelis Till Roenneberg Fang Zheng Christian Alzheimer Alcino Silva Wolfgang Wurst Ralf Kühn MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults. PLoS ONE |
| title | MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults. |
| title_full | MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults. |
| title_fullStr | MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults. |
| title_full_unstemmed | MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults. |
| title_short | MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults. |
| title_sort | mapk signaling determines anxiety in the juvenile mouse brain but depression like behavior in adults |
| url | http://europepmc.org/articles/PMC3329550?pdf=render |
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