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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)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter M3/6; Jnk; Inflammation; Anxiety; Stress; Memory; Brain
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 19483 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Developmental Genetics (IDG)
CF Pathology & Tissue Analytics (CF-PTA)
Institute of Experimental Genetics (IEG)
Research Unit Analytical Pathology (AAP)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
30204 - Cell Programming and Repair
30505 - New Technologies for Biomedical Discoveries
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Helmholtz Diabetes Center
Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-502294-001
G-502400-001
G-500500-001
A-630600-001
G-500692-001
G-500390-001
G-500600-001
G-502200-001
DOI 10.1038/s41598-019-55527-7
WOS ID WOS:000508868500008
Scopus ID 85076909065
PubMed ID 31862894
Erfassungsdatum 2019-12-23
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