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Baumann, P. ; Schriever, S.C. ; Kullmann, S. ; Zimprich, A.* ; Feuchtinger, A. ; Amarie, O.V. ; Peter, A. ; Walch, A.K. ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; Wurst, W. ; Tschöp, M.H. ; Heni, M. ; Hölter, S.M. ; Pfluger, P.T.

Dusp8 affects hippocampal size and behavior in mice and humans.

Sci. Rep. 9:19483 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Dual-specificity phosphatase 8 (Dusp8) acts as physiological inhibitor for the MAPKs Jnk, Erk and p38 which are involved in regulating multiple CNS processes. While Dusp8 expression levels are high in limbic areas such as the hippocampus, the functional role of Dusp8 in hippocampus morphology, MAPK-signaling, neurogenesis and apoptosis as well as in behavior are still unclear. It is of particular interest whether human carriers of a DUSP8 allelic variant show similar hippocampal alterations to mice. Addressing these questions using Dusp8WT and KO mouse littermates, we found that KOs suffered from mildly impaired spatial learning, increased locomotor activity and elevated anxiety. Cell proliferation, apoptosis and p38 and Jnk phosphorylation were unaffected, but phospho-Erk levels were higher in hippocampi of the KOs. Consistent with a decreased hippocampus size in Dusp8 KO mice, we found reduced volumes of the hippocampal subregions subiculum and CA4 in humans carrying the DUSP8 allelic variant SNP rs2334499:C > T. Overall, aberrations in morphology and behavior in Dusp8 KO mice and a decrease in hippocampal volume of SNP rs2334499:C > T carriers point to a novel, translationally relevant role of Dusp8 in hippocampus function that warrants further studies on the role of Dusp8 within the limbic network.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords M3/6; Jnk; Inflammation; Anxiety; Stress; Memory; Brain
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Journal Scientific Reports
Quellenangaben Volume: 9, Issue: 1, Pages: , Article Number: 19483 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Developmental Genetics (IDG)
Research Unit Analytical Pathology (AAP)
Institute of Experimental Genetics (IEG)