Methionine mediates resilience to chronic social defeat stress by epigenetic regulation of NMDA receptor subunit express
- PDF / 1,015,471 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 40 Downloads / 170 Views
ORIGINAL INVESTIGATION
Methionine mediates resilience to chronic social defeat stress by epigenetic regulation of NMDA receptor subunit expression Maria Bilen 1,2 & Pascal Ibrahim 1,3 & Nour Barmo 1 & Edwina Abou Haidar 1 & Nabil Karnib 1,4 & Lauretta El Hayek 1,5 & Mohamad Khalifeh 1 & Vanessa Jabre 1 & Rouba Houbeika 1 & Joseph S. Stephan 6 & Sama F. Sleiman 1 Received: 25 July 2019 / Accepted: 11 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Previous studies suggested that methionine (Met) levels are decreased in depressed patients. However, whether the decrease in this amino acid is important for phenotypic behaviors associated with depression has not been deciphered. Objective The response of individuals to chronic stress is variable, with some individuals developing depression and others becoming resilient to stress. In this study, our objective was to examine the effect of Met on susceptibility to stress. Methods Male C57BL/6J mice were subjected to daily defeat sessions by a CD1 aggressor, for 10 days. On day 11, the behavior of mice was assessed using social interaction and open-field tests. Mice received Met 4 h before each defeat session. Epigenetic targets were assessed either through real-rime RTPCR or through Western Blots. Results Met did not modulate anxiety-like behaviors, but rather promoted resilience to chronic stress, rescued social avoidance behaviors and reversed the increase in the cortical expression levels of N-methyl-D -aspartate receptor (NMDAR) subunits. Activating NMDAR activity abolished the ability of Met to promote resilience to stress and to rescue social avoidance behavior, whereas inhibiting NMDAR did not show any synergistic or additive protective effects. Indeed, Met increased the cortical levels of the histone methyltransferase SETDB1, and in turn, the levels of the repressive histone H3 lysine (K9) trimethylation (me3). Conclusions Our data indicate that Met rescues susceptibility to stress by inactivating cortical NMDAR activity through an epigenetic mechanism involving histone methylation. Keywords Methionine . Grin1 . Grin2 . Chronic social defeat stress . SETDB1 . Depression . Histone H3K9 trimethylation
Introduction Maria Bilen, Pascal Ibrahim and Nour Barmo contributed equally to this work. * Sama F. Sleiman [email protected] 1
Biological Sciences Program, Department of Natural Sciences, Lebanese American University, PO Box 36, Byblos, Lebanon
2
Faculty of Medicine, University of Ottawa, Ottawa, Canada
3
Department of Psychiatry, McGill University, Montreal, Canada
4
Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, USA
5
Biological Sciences Program, University of Texas Southwestern, Dallas, TX, USA
6
School of Medicine, Lebanese American University, PO Box 36, Byblos, Lebanon
Depression is a leading cause of disability worldwide (Nestler et al. 2016; Smith 2014). Most of our understanding of the molecular basis of depression came about from studying the effects of chr
Data Loading...
