Published in

Public Library of Science, PLoS ONE, 4(7), p. e35035, 2012

DOI: 10.1371/journal.pone.0035035

Links

Tools

Export citation

Search in Google Scholar

MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults.

Journal article published in 2012 by Benedikt Wefers, Christiane Hitz, Sabine M. Hölter ORCID, Dietrich Trümbach, Jens Hansen, Peter Weber, Benno Pütz ORCID, Jan M. Deussing, Martin Hrabé de Angelis ORCID, M. Hrabě de Angelis, Till Roenneberg, Fang Zheng, Christian Alzheimer, Alcino Silva, Wolfgang Wurst ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Green circle
Postprint: archiving allowed
Upload
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

Abstract

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.