Fluoxetine Treatment Rescues Energy Metabolism Pathway Alterations in a Posttraumatic Stress Disorder Mouse Model.
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock-induced PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo (15)N metabolic labeling combined with mass spectrometry in the prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala, central nucleus of the amygdala and CA1 of the hippocampus between shocked and nonshocked (control) mice, with and without fluoxetine treatment. In silico pathway analyses revealed an upregulation of the citric acid cycle pathway in PrL, and downregulation in ACC and nucleus accumbens (NAc). Chronic fluoxetine treatment prevented decreased citric acid cycle activity in NAc and ACC and ameliorated conditioned fear response in shocked mice. Our results shed light on the role of energy metabolism in PTSD pathogenesis and suggest potential therapy through mitochondrial targeting.
Departments of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany; Graduate School of Systemic Neurosciences, Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
Chi-Ya
CY
Kao
CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Zhisong
Z
He
Departments of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
Kathrin
K
Henes
Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, Mass., USA.
John M
JM
Asara
Departments of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Christian
C
Webhofer
Departments of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Michaela D
MD
Filiou
CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Philipp
P
Khaitovich
Departments of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany; Graduate School of Systemic Neurosciences, Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
Carsten T
CT
Wotjak
Departments of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany; Graduate School of Systemic Neurosciences, Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
Christoph W
CW
Turck
Anterior cingulate cortex; Energy metabolism; Fluoxetine; Nucleus accumbens; Posttraumatic stress disorder model