title: Serum Response Factor (SRF) Ablation Interferes with Acute Stress-Associated Immediate and Long-Term Coping Mechanisms.
abstract: Stress experience modulates behavior, metabolism, and energy expenditure of organisms. One molecular hallmark of an acute stress response is a rapid induction of immediate early genes (IEGs) such as c-Fos and Egr family members. IEG transcription in neurons is mediated by the neuronal activity-driven gene regulator serum response factor (SRF). We show a first role of SRF in immediate and long-lasting acute restraint stress (AS) responses. For this, we employed a standardized mouse phenotyping protocol at the German Mouse Clinic (GMC) including behavioral, metabolic, and cardiologic tests as well as gene expression profiling to analyze the consequences of forebrain-specific SRF deletion in mice exposed to AS. Adult mice with an SRF deletion in glutamatergic neurons (Srf;CaMKIIa-CreERT2) showed hyperactivity, decreased anxiety, and impaired working memory. In response to restraint AS, instant stress reactivity including locomotor behavior and corticosterone induction was impaired in Srf mutant mice. Interestingly, even several weeks after previous AS exposure, SRF-deficient mice showed long-lasting AS-associated changes including altered locomotion, metabolism, energy expenditure, and cardiovascular changes. This suggests a requirement of SRF for mediating long-term stress coping mechanisms in wild-type mice. SRF ablation decreased AS-mediated IEG induction and activity of the actin severing protein cofilin. In summary, our data suggest an SRF function in immediate AS reactions and long-term post-stress-associated coping mechanisms.
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Institute of Developmental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Zimprich
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Mroz
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Meyer Zu Reckendorf
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Sofia
authors.initials: S
authors.lastname: Anastasiadou
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Förstner
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Institute of Developmental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Lillian
authors.initials: L
authors.lastname: Garrett
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Institute of Developmental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Lore
authors.initials: L
authors.lastname: Becker
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Ingostädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.|German Center for Diabetes Research (DZD), Ingostädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Moreth
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.|Chair of Developmental Genetics, Technische Universität München-Weihenstephan, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.|German Center for Neurodegenerative Diseases (DZNE), Munich Site, Feodor-Lynen-Strasse 17, 81377, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, Schillerstr. 44, 80336, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Munich Site, Feodor-Lynen-Strasse 17, 81377, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, Schillerstr. 44, 80336, Munich, Germany.|Department of Neurology, Friedrich-Baur-Institute, Klinikum der Ludwig-Maximilians-Universität München, Ziemssenstr. 1a, 80336, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.affiliation: Molecular Nutritional Medicine Else Kröner-Fresenius Center, Technische Universität München, 85354, Freising-Weihenstephan, Germany.|ZIEL-Center for Nutrition and Food Sciences, Technische Universität München, 85350, Freising, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Chair of Experimental Genetics, School of Life Science Weihenstephan Technische Universität München, Alte Akademie 8, 85354, Freising, Germany.|German Center for Diabetes Research (DZD), Ingostädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Department of Cardiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
authors.forename: Raffi
authors.initials: R
authors.lastname: Bekeredjian
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Gailus-Durner
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Chair of Experimental Genetics, School of Life Science Weihenstephan Technische Universität München, Alte Akademie 8, 85354, Freising, Germany.|German Center for Diabetes Research (DZD), Ingostädter Landstr. 1, 85764, Neuherberg, Germany.
authors.forename: Martin Hrabe
authors.initials: MH
authors.lastname: de Angelis
authors.affiliation: Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany. bernd.knoell@uni-ulm.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Knöll
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D005260:Female; D017781:Genes, Immediate-Early / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology; D026362:Serum Response Factor / Q000172:deficiency* / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D026362:Serum Response Factor
keywords: Acute stress; Cofilin; Fos; Hyperactivity; Immediate early gene; SRF