Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling
How individuals respond to chronic stress varies. Susceptible individuals ultimately develop depression; whereas resilient individuals live normally. In this study, our objective was to examine the effect of branched-chain amino acids (BCAA), commonly used by athletes, on susceptibility to stress. M...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , |
| التنسيق: | article |
| منشور في: |
2019
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/11420 https://doi.org/10.1016/j.ynstr.2019.100170 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S2352289519300153 |
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| _version_ | 1864513488752214016 |
|---|---|
| author | Nasrallah, Patrick |
| author2 | Abou Haidar, Edwina Stephan, Joseph S. El Hayek, Lauretta Karnib, Nabil Khalifeh, Mohamad Barmo, Nour Jabre, Vanessa Houbeika, Rouba Ghanem, Anthony Nasser, Jason Zeeni, Nadine Bassil, Maya F. Sleiman, Sama |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Nasrallah, Patrick Abou Haidar, Edwina Stephan, Joseph S. El Hayek, Lauretta Karnib, Nabil Khalifeh, Mohamad Barmo, Nour Jabre, Vanessa Houbeika, Rouba Ghanem, Anthony Nasser, Jason Zeeni, Nadine Bassil, Maya F. Sleiman, Sama |
| author_role | author |
| dc.creator.none.fl_str_mv | Nasrallah, Patrick Abou Haidar, Edwina Stephan, Joseph S. El Hayek, Lauretta Karnib, Nabil Khalifeh, Mohamad Barmo, Nour Jabre, Vanessa Houbeika, Rouba Ghanem, Anthony Nasser, Jason Zeeni, Nadine Bassil, Maya F. Sleiman, Sama |
| dc.date.none.fl_str_mv | 2019-10-11T12:11:13Z 2019-10-11T12:11:13Z 2019 2019-10-11 |
| dc.identifier.none.fl_str_mv | 2352-2895 http://hdl.handle.net/10725/11420 https://doi.org/10.1016/j.ynstr.2019.100170 Nasrallah, P., Haidar, E. A., Stephan, J. S., El Hayek, L., Karnib, N., Khalifeh, M., ... & Nasser, J. (2019). Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling. Neurobiology of stress, 11, 100170. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S2352289519300153 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Neurobiology of Stress |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | How individuals respond to chronic stress varies. Susceptible individuals ultimately develop depression; whereas resilient individuals live normally. In this study, our objective was to examine the effect of branched-chain amino acids (BCAA), commonly used by athletes, on susceptibility to stress. Male C57BL/6 mice were subjected to daily defeat sessions by a CD1 aggressor, for 10 days. On day11, the behavior of mice was assessed using the social interaction test, elevated plus maze and open field. Mice received the BCAA leucine, isoleucine or valine before each defeat session. Furthermore, we examined whether BCAA regulate brain derived neurotrophic factor (BDNF) signaling by using a brain-permeable tropomyosin receptor kinase B (TRKB) inhibitor, ANA-12. We also tested the effect of voluntary exercise and high protein diets on susceptibility to stress. Mice exposed to chronic stress displayed increased susceptibility and social avoidance. BCAA promoted resilience to chronic stress, rescued social avoidance behaviors and increased hippocampal BDNF levels and TRKB activation. Inhibition of TRKB signaling abolished the ability of BCAA to promote resilience to stress and to rescue social avoidance. Interestingly, we found that BCAA activate the exercise-regulated PGC1a/FNDC5 pathway known to induce hippocampal BDNF signaling. Although both voluntary exercise and BCAA promoted resilience to stress, combining them did not yield synergistic effects confirming that they affect similar pathways. We also discovered that high protein diets mimic the effect of BCAA by rescuing social deficits induced by chronic stress and increase Bdnf expression in the hippocampus. Our data indicate that BCAA, exercise and high protein diets rescue susceptibility to stress by activating the hippocampal BDNF/TRKB signaling. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_5316ef4ce4e4df8aaa79b9ae44355168 |
| identifier_str_mv | 2352-2895 Nasrallah, P., Haidar, E. A., Stephan, J. S., El Hayek, L., Karnib, N., Khalifeh, M., ... & Nasser, J. (2019). Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling. Neurobiology of stress, 11, 100170. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/11420 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signalingNasrallah, PatrickAbou Haidar, EdwinaStephan, Joseph S.El Hayek, LaurettaKarnib, NabilKhalifeh, MohamadBarmo, NourJabre, VanessaHoubeika, RoubaGhanem, AnthonyNasser, JasonZeeni, NadineBassil, MayaF. Sleiman, SamaHow individuals respond to chronic stress varies. Susceptible individuals ultimately develop depression; whereas resilient individuals live normally. In this study, our objective was to examine the effect of branched-chain amino acids (BCAA), commonly used by athletes, on susceptibility to stress. Male C57BL/6 mice were subjected to daily defeat sessions by a CD1 aggressor, for 10 days. On day11, the behavior of mice was assessed using the social interaction test, elevated plus maze and open field. Mice received the BCAA leucine, isoleucine or valine before each defeat session. Furthermore, we examined whether BCAA regulate brain derived neurotrophic factor (BDNF) signaling by using a brain-permeable tropomyosin receptor kinase B (TRKB) inhibitor, ANA-12. We also tested the effect of voluntary exercise and high protein diets on susceptibility to stress. Mice exposed to chronic stress displayed increased susceptibility and social avoidance. BCAA promoted resilience to chronic stress, rescued social avoidance behaviors and increased hippocampal BDNF levels and TRKB activation. Inhibition of TRKB signaling abolished the ability of BCAA to promote resilience to stress and to rescue social avoidance. Interestingly, we found that BCAA activate the exercise-regulated PGC1a/FNDC5 pathway known to induce hippocampal BDNF signaling. Although both voluntary exercise and BCAA promoted resilience to stress, combining them did not yield synergistic effects confirming that they affect similar pathways. We also discovered that high protein diets mimic the effect of BCAA by rescuing social deficits induced by chronic stress and increase Bdnf expression in the hippocampus. Our data indicate that BCAA, exercise and high protein diets rescue susceptibility to stress by activating the hippocampal BDNF/TRKB signaling.PublishedN/A2019-10-11T12:11:13Z2019-10-11T12:11:13Z20192019-10-11Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2352-2895http://hdl.handle.net/10725/11420https://doi.org/10.1016/j.ynstr.2019.100170Nasrallah, P., Haidar, E. A., Stephan, J. S., El Hayek, L., Karnib, N., Khalifeh, M., ... & Nasser, J. (2019). Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling. Neurobiology of stress, 11, 100170.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://www.sciencedirect.com/science/article/pii/S2352289519300153enNeurobiology of Stressinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/114202021-03-19T10:47:37Z |
| spellingShingle | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling Nasrallah, Patrick |
| status_str | publishedVersion |
| title | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling |
| title_full | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling |
| title_fullStr | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling |
| title_full_unstemmed | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling |
| title_short | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling |
| title_sort | Branched-chain amino acids mediate resilience to chronic social defeat stress by activating BDNF/TRKB signaling |
| url | http://hdl.handle.net/10725/11420 https://doi.org/10.1016/j.ynstr.2019.100170 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://www.sciencedirect.com/science/article/pii/S2352289519300153 |