title: Rapid stress-induced transcriptomic changes in the brain depend on beta-adrenergic signaling.
abstract: Acute exposure to stressful experiences can rapidly increase anxiety and cause neuropsychiatric disorders. The effects of stress result in part from the release of neurotransmitters and hormones, which regulate gene expression in different brain regions. The fast neuroendocrine response to stress is largely mediated by norepinephrine (NE) and corticotropin releasing hormone (CRH), followed by a slower and more sustained release of corticosterone. While corticosterone is an important regulator of gene expression, it is not clear which stress-signals contribute to the rapid regulation of gene expression observed immediately after stress exposure. Here, we demonstrate in mice that 45 min after an acute swim stress challenge, large changes in gene expression occur across the transcriptome in the hippocampus, a region sensitive to the effects of stress. We identify multiple candidate genes that are rapidly and transiently altered in both males and females. Using a pharmacological approach, we show that most of these rapidly induced genes are regulated by NE through β-adrenergic receptor signaling. We find that CRH and corticosterone can also contribute to rapid changes in gene expression, although these effects appear to be restricted to fewer genes. These results newly reveal a widespread impact of NE on the transcriptome and identify novel genes associated with stress and adrenergic signaling.
authors.affiliation: Laboratory of Neuroepigenetics, Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Roszkowski
authors.affiliation: Laboratory of Neuroepigenetics, Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Manuella
authors.affiliation: Laboratory of Neuroepigenetics, Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: von Ziegler
authors.affiliation: Pharma Research and Early Development, Pharmaceutical Sciences, Translational Technologies and Bioinformatics, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Durán-Pacheco
authors.affiliation: Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Moreau
authors.affiliation: Laboratory of Neuroepigenetics, Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Mansuy
authors.affiliation: Laboratory of Neuroepigenetics, Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. Electronic address: bohacek@hifo.uzh.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bohacek
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D059467:Transcriptome / Q000502:physiology*
chemical_list: D011943:Receptors, Adrenergic, beta; D003345:Corticosterone; D009638:Norepinephrine
keywords: Corticosterone; Corticotropin releasing hormone; Gene expression; Hippocampus; Noradrenaline; Norepinephrine; Stress; Transcriptome