title: Fluoxetine treatment prevents the inflammatory response in a mouse model of posttraumatic stress disorder.
abstract: Despite intense research efforts the molecular mechanisms affecting stress-vulnerable brain regions in posttraumatic stress disorder (PTSD) remain elusive. In the current study we have applied global transcriptomic profiling to a PTSD mouse model induced by foot shock fear conditioning. We compared the transcriptomes of prelimbic cortex, anterior cingulate cortex (ACC), basolateral amygdala, central nucleus of amygdala, nucleus accumbens (NAc) and CA1 of the dorsal hippocampus between shocked and non-shocked (control) mice, with and without fluoxetine treatment by RNA sequencing. Differentially expressed (DE) genes were identified and clustered for in silico pathway analysis. Findings in relevant brain regions were further validated with immunohistochemistry. DE genes belonging to 11 clusters were identified including increased inflammatory response in ACC in shocked mice. In line with this finding, we noted higher microglial activation in ACC of shocked mice. Chronic fluoxetine treatment initiated in the aftermath of the trauma prevented inflammatory gene expression alterations in ACC and ameliorated PTSD-like symptoms, implying an important role of the immune response in PTSD pathobiology. Our results provide novel insights into molecular mechanisms affected in PTSD and suggest therapeutic applications with anti-inflammatory agents.
authors.affiliation: Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany; Graduate School of Systemic Neurosciences, Ludwig-Maximilians-University Munich, Grosshadernerstr. 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Chi-Ya
authors.initials: CY
authors.lastname: Kao
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road Shanghai, People's Republic of China.
authors.forename: Zhisong
authors.initials: Z
authors.lastname: He
authors.affiliation: Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 27710 Durham, NC, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Zannas
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road Shanghai, People's Republic of China.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hahn
authors.affiliation: Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kühne
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, Kraepelinstrasse 2-10, 80804 Munich, Germany.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Reichel
authors.affiliation: Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany; Department of Psychiatry and Behavioral Sciences, Emory University Medical School, 30307 Atlanta, GA, USA.
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.affiliation: Max Planck Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, Kraepelinstrasse 2-10, 80804 Munich, Germany.
authors.forename: Carsten T
authors.initials: CT
authors.lastname: Wotjak
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road Shanghai, People's Republic of China. Electronic address: khaitovich@eva.mpg.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
authors.affiliation: Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. Electronic address: turck@psych.mpg.de.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D005239:Fear / Q000523:psychology; D005473:Fluoxetine / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D018687:Antidepressive Agents, Second-Generation; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D005473:Fluoxetine
keywords: Anterior cingulate cortex; Fluoxetine; Inflammatory pathways; PTSD model