Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression.

Autor:	Privitera M; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland., von Ziegler LM; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland., Floriou-Servou A; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland., Duss SN; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland., Zhang R; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Waag R; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland., Leimbacher S; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Sturman O; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland., Roessler FK; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland., Heylen A; Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium., Vermeiren Y; Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Division of Human Nutrition and Health, Chair Group of Nutritional Biology, Wageningen University & Research (WUR), Wageningen, Netherlands., Van Dam D; Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, Netherlands., De Deyn PP; Laboratory of Neurochemistry and Behavior, Experimental Neurobiology Unit, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.; Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, Netherlands.; Department of Neurology, Memory Clinic of Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium., Germain PL; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland.; Computational Neurogenomics, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zürich, Zurich, Switzerland.; Laboratory of Statistical Bioinformatics, University of Zürich, Zürich, Switzerland., Bohacek J; Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.; Neuroscience Center Zurich, ETH Zurich and University of Zurich, Switzerland, Zurich, Switzerland.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Mar 13; Vol. 12. Date of Electronic Publication: 2024 Mar 13.
DOI:	10.7554/eLife.88559
Abstrakt:	Exposure to an acute stressor triggers a complex cascade of neurochemical events in the brain. However, deciphering their individual impact on stress-induced molecular changes remains a major challenge. Here, we combine RNA sequencing with selective pharmacological, chemogenetic, and optogenetic manipulations to isolate the contribution of the locus coeruleus-noradrenaline (LC-NA) system to the acute stress response in mice. We reveal that NA release during stress exposure regulates a large and reproducible set of genes in the dorsal and ventral hippocampus via β-adrenergic receptors. For a smaller subset of these genes, we show that NA release triggered by LC stimulation is sufficient to mimic the stress-induced transcriptional response. We observe these effects in both sexes, and independent of the pattern and frequency of LC activation. Using a retrograde optogenetic approach, we demonstrate that hippocampus-projecting LC neurons directly regulate hippocampal gene expression. Overall, a highly selective set of astrocyte-enriched genes emerges as key targets of LC-NA activation, most prominently several subunits of protein phosphatase 1 ( Ppp1r3c , Ppp1r3d , Ppp1r3g ) and type II iodothyronine deiodinase ( Dio2 ). These results highlight the importance of astrocytic energy metabolism and thyroid hormone signaling in LC-mediated hippocampal function and offer new molecular targets for understanding how NA impacts brain function in health and disease. Competing Interests: MP, Lv, AF, SD, RZ, RW, SL, OS, FR, AH, YV, DV, PD, PG, JB No competing interests declared (© 2023, Privitera et al.)
Databáze:	MEDLINE
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