Chronic Psychosocial Stress in Mice Is Associated With Increased Acid Sphingomyelinase Activity in Liver and Serum and With Hepatic C16:0-Ceramide Accumulation

Frontiers in Psychiatry

Andrea M. Füchsl¹  Erich Gulbins²  Martin Reichel³  Johannes Kornhuber⁴  Cosima Rhein⁴  Lena M. Hofmann⁴  Juliana Monti⁴  Claus Hellerbrand⁵  Burkhard Kleuser⁶  Lukasz Japtok⁶  Stefan O. Reber⁷  Dominik Langgartner⁷ 

[1] Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany;Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany;Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany;Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany;Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany;Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany;Laboratory for Molecular Psychosomatics, Clinic for Psychosomatic Medicine and Psychotherapy, University of Ulm, Ulm, Germany;

关键词: chronic psychosocial stress;    acid sphingomyelinase;    ceramide;    sphingolipid metabolism;    chronic subordinate colony housing (CSC);    liver metabolism;   

DOI  :  10.3389/fpsyt.2018.00496

来源: DOAJ

【 摘 要 】

Chronic psychosocial stress adversely affects human morbidity and is a risk factor for inflammatory disorders, liver diseases, obesity, metabolic syndrome, and major depressive disorder (MDD). In recent studies, we found an association of MDD with an increase of acid sphingomyelinase (ASM) activity. Thus, we asked whether chronic psychosocial stress as a detrimental factor contributing to the emergence of MDD would also affect ASM activity and sphingolipid (SL) metabolism. To induce chronic psychosocial stress in male mice we employed the chronic subordinate colony housing (CSC) paradigm and compared them to non-stressed single housed control (SHC) mice. We determined Asm activity in liver and serum, hepatic SL concentrations as well as hepatic mRNA expression of genes involved in SL metabolism. We found that hepatic Asm activity was increased by 28% (P = 0.006) and secretory Asm activity by 47% (P = 0.002) in stressed mice. C16:0-Cer was increased by 40% (P = 0.008). Gene expression analysis further revealed an increased expression of tumor necrosis factor (TNF)-α (P = 0.009) and of several genes involved in SL metabolism (Cers5, P = 0.028; Cers6, P = 0.045; Gba, P = 0.049; Gba2, P = 0.030; Ormdl2, P = 0.034; Smpdl3B; P = 0.013). Our data thus provides first evidence that chronic psychosocial stress, at least in mice, induces alterations in SL metabolism, which in turn might be involved in mediating the adverse health effects of chronic psychosocial stress and peripheral changes occurring in mood disorders.

【 授权许可】

Unknown