Skip to main content
Top
Published in: NeuroMolecular Medicine 2/2018

01-06-2018 | Original Paper

BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress

Authors: Le Wei, Li-Yuan Kan, Hai-Ying Zeng, Yi-Yun Tang, Hong-Lin Huang, Ming Xie, Wei Zou, Chun-Yan Wang, Ping Zhang, Xiao-Qing Tang

Published in: NeuroMolecular Medicine | Issue 2/2018

Login to get access

Abstract

Our previous works have shown that hydrogen sulfide (H2S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H2S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors.
Literature
go back to reference Abe, K., & Kimura, H. (1996). The possible role of hydrogen sulfide as an endogenous neuromodulator. Journal of Neuroscience, 16(3), 1066–1071.CrossRefPubMed Abe, K., & Kimura, H. (1996). The possible role of hydrogen sulfide as an endogenous neuromodulator. Journal of Neuroscience, 16(3), 1066–1071.CrossRefPubMed
go back to reference Ivanova, T., & Beyer, C. (2001). Pre- and postnatal expression of brain-derived neurotrophic factor mRNA/protein and tyrosine protein kinase receptor B mRNA in the mouse hippocampus. Neuroscience Letters, 307(1), 21–24.CrossRefPubMed Ivanova, T., & Beyer, C. (2001). Pre- and postnatal expression of brain-derived neurotrophic factor mRNA/protein and tyrosine protein kinase receptor B mRNA in the mouse hippocampus. Neuroscience Letters, 307(1), 21–24.CrossRefPubMed
go back to reference Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., & Aubry, J. M. (2002). Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Research, 109(2), 143–148.CrossRefPubMed Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., & Aubry, J. M. (2002). Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Research, 109(2), 143–148.CrossRefPubMed
go back to reference Li, L. F., Lu, J., Li, X. M., Xu, C. L., Deng, J. M., Qu, R., et al. (2012). Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats. Phytotherapy Research, 26(8), 1189–1194. https://doi.org/10.1002/ptr.3706.CrossRefPubMed Li, L. F., Lu, J., Li, X. M., Xu, C. L., Deng, J. M., Qu, R., et al. (2012). Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats. Phytotherapy Research, 26(8), 1189–1194. https://​doi.​org/​10.​1002/​ptr.​3706.CrossRefPubMed
go back to reference Lowicka, E., & Beltowski, J. (2007). Hydrogen sulfide (H2S): The third gas of interest for pharmacologists. Pharmacological Reports, 59(1), 4–24.PubMed Lowicka, E., & Beltowski, J. (2007). Hydrogen sulfide (H2S): The third gas of interest for pharmacologists. Pharmacological Reports, 59(1), 4–24.PubMed
go back to reference Lyons, W. E., Mamounas, L. A., Ricaurte, G. A., Coppola, V., Reid, S. W., Bora, S. H., et al. (1999). Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proceedings of the National Academy of Sciences, 96(26), 15239–15244.CrossRef Lyons, W. E., Mamounas, L. A., Ricaurte, G. A., Coppola, V., Reid, S. W., Bora, S. H., et al. (1999). Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proceedings of the National Academy of Sciences, 96(26), 15239–15244.CrossRef
go back to reference Porsolt, R. D., Le Pichon, M., & Jalfre, M. (1977). Depression: A new animal model sensitive to antidepressant treatments. Nature, 266(5604), 730–732.CrossRefPubMed Porsolt, R. D., Le Pichon, M., & Jalfre, M. (1977). Depression: A new animal model sensitive to antidepressant treatments. Nature, 266(5604), 730–732.CrossRefPubMed
go back to reference Rantamaki, T., Hendolin, P., Kankaanpaa, A., Mijatovic, J., Piepponen, P., Domenici, E., et al. (2007). Pharmacologically diverse antidepressants rapidly activate brain-derived neurotrophic factor receptor TrkB and induce phospholipase-Cgamma signaling pathways in mouse brain. Neuropsychopharmacology, 32(10), 2152–2162. https://doi.org/10.1038/sj.npp.1301345.CrossRefPubMed Rantamaki, T., Hendolin, P., Kankaanpaa, A., Mijatovic, J., Piepponen, P., Domenici, E., et al. (2007). Pharmacologically diverse antidepressants rapidly activate brain-derived neurotrophic factor receptor TrkB and induce phospholipase-Cgamma signaling pathways in mouse brain. Neuropsychopharmacology, 32(10), 2152–2162. https://​doi.​org/​10.​1038/​sj.​npp.​1301345.CrossRefPubMed
go back to reference Rutkowski, D. T., & Kaufman, R. J. (2004). A trip to the ER: Coping with stress. Trends in Cell Biology, 14(1), 20–28.CrossRefPubMed Rutkowski, D. T., & Kaufman, R. J. (2004). A trip to the ER: Coping with stress. Trends in Cell Biology, 14(1), 20–28.CrossRefPubMed
go back to reference Saarelainen, T., Hendolin, P., Lucas, G., Koponen, E., Sairanen, M., MacDonald, E., et al. (2003). Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. Journal of Neuroscience, 23(1), 349–357.CrossRefPubMed Saarelainen, T., Hendolin, P., Lucas, G., Koponen, E., Sairanen, M., MacDonald, E., et al. (2003). Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. Journal of Neuroscience, 23(1), 349–357.CrossRefPubMed
go back to reference Shimizu, E., Hashimoto, K., Okamura, N., Koike, K., Komatsu, N., Kumakiri, C., et al. (2003). Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biological Psychiatry, 54(1), 70–75.CrossRefPubMed Shimizu, E., Hashimoto, K., Okamura, N., Koike, K., Komatsu, N., Kumakiri, C., et al. (2003). Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biological Psychiatry, 54(1), 70–75.CrossRefPubMed
go back to reference Shirayama, Y., Chen, A. C., Nakagawa, S., Russell, D. S., & Duman, R. S. (2002). Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. Journal of Neuroscience, 22(8), 3251–3261.CrossRefPubMed Shirayama, Y., Chen, A. C., Nakagawa, S., Russell, D. S., & Duman, R. S. (2002). Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. Journal of Neuroscience, 22(8), 3251–3261.CrossRefPubMed
go back to reference Tan, H., Zou, W., Jiang, J., Tian, Y., Xiao, Z., Bi, L., et al. (2015). Disturbance of hippocampal H2S generation contributes to CUMS-induced depression-like behavior: Involvement in endoplasmic reticulum stress of hippocampus. Acta Biochimica et Biophysica Sinica (Shanghai), 47(4), 285–291. https://doi.org/10.1093/abbs/gmv009.CrossRef Tan, H., Zou, W., Jiang, J., Tian, Y., Xiao, Z., Bi, L., et al. (2015). Disturbance of hippocampal H2S generation contributes to CUMS-induced depression-like behavior: Involvement in endoplasmic reticulum stress of hippocampus. Acta Biochimica et Biophysica Sinica (Shanghai), 47(4), 285–291. https://​doi.​org/​10.​1093/​abbs/​gmv009.CrossRef
go back to reference Willner, P. (1997). Validity, reliability and utility of the chronic mild stress model of depression: A 10-year review and evaluation. Psychopharmacology (Berl), 134(4), 319–329.CrossRef Willner, P. (1997). Validity, reliability and utility of the chronic mild stress model of depression: A 10-year review and evaluation. Psychopharmacology (Berl), 134(4), 319–329.CrossRef
go back to reference Zhao, T., Huang, G. B., Muna, S. S., Bagalkot, T. R., Jin, H. M., Chae, H. J., et al. (2013). Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78-kDa glucose-regulated protein, and CCAAT/enhancer-binding protein (C/EBP) homologous protein in adult mice. Psychopharmacology (Berl), 228(2), 217–230. https://doi.org/10.1007/s00213-013-3028-6.CrossRef Zhao, T., Huang, G. B., Muna, S. S., Bagalkot, T. R., Jin, H. M., Chae, H. J., et al. (2013). Effects of chronic social defeat stress on behavior and choline acetyltransferase, 78-kDa glucose-regulated protein, and CCAAT/enhancer-binding protein (C/EBP) homologous protein in adult mice. Psychopharmacology (Berl), 228(2), 217–230. https://​doi.​org/​10.​1007/​s00213-013-3028-6.CrossRef
Metadata
Title
BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress
Authors
Le Wei
Li-Yuan Kan
Hai-Ying Zeng
Yi-Yun Tang
Hong-Lin Huang
Ming Xie
Wei Zou
Chun-Yan Wang
Ping Zhang
Xiao-Qing Tang
Publication date
01-06-2018
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 2/2018
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-018-8489-7

Other articles of this Issue 2/2018

NeuroMolecular Medicine 2/2018 Go to the issue