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Zimprich, A. ; Mroz, G.* ; Meyer Zu Reckendorf, C.* ; Anastasiadou, S.* ; Förstner, P.* ; Garrett, L. ; Hölter, S.M. ; Becker, L. ; Rozman, J. ; Prehn, C. ; Rathkolb, B. ; Moreth, K. ; Wurst, W. ; Klopstock, T.* ; Klingenspor, M.* ; Adamski, J. ; Wolf, E.* ; Bekeredjian, R.* ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Knöll, B.*

Serum response factor (SRF) ablation interferes with acute stress-associated immediate and long-term coping mechanisms.

Mol. Neurobiol. 54, 8242–8262 (2016)
Forschungsdaten DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acute Stress ; Cofilin ; Fos ; Hyperactivity ; Immediate Early Gene ; Srf; Early Gene-expression; C-fos Expression; Delta-fosb; Nervous-system; Antidepressant Responses; Recognition Memory; Restraint Stress; Reduced Anxiety; Adrenal Axis; Rat-brain
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 0893-7648
e-ISSN 1559-1182
Zeitschrift Molecular Neurobiology
Quellenangaben Band: 54, Heft: 10, Seiten: 8242–8262 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Clifton, NJ
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Molekulare Endokrinologie und Metabolismus (MEM)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30204 - Cell Programming and Repair
30201 - Metabolic Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-007
G-500500-001
G-500600-001
G-500600-003
G-505600-001
G-501900-061
G-500692-001
DOI 10.1007/s12035-016-0300-x
WOS ID WOS:000415341900057
Scopus ID 85001104593
Erfassungsdatum 2016-12-23
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