PMID- 29704115 OWN - NLM STAT- MEDLINE DCOM- 20190731 LR - 20220408 IS - 1559-1174 (Electronic) IS - 1535-1084 (Linking) VI - 20 IP - 2 DP - 2018 Jun TI - BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H(2)S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress. PG - 252-261 LID - 10.1007/s12017-018-8489-7 [doi] AB - Our previous works have shown that hydrogen sulfide (H(2)S) 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 H(2)S 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 H(2)S 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 H(2)S) 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 H(2)S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H(2)S against CUMS-induced depressive-like behaviors. FAU - Wei, Le AU - Wei L AD - Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, 28 West Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. FAU - Kan, Li-Yuan AU - Kan LY AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. AD - Department of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China. FAU - Zeng, Hai-Ying AU - Zeng HY AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. AD - Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China. FAU - Tang, Yi-Yun AU - Tang YY AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. FAU - Huang, Hong-Lin AU - Huang HL AD - Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, 28 West Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. huanghonglinhui@aliyun.com. FAU - Xie, Ming AU - Xie M AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. AD - Department of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China. FAU - Zou, Wei AU - Zou W AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. AD - Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China. FAU - Wang, Chun-Yan AU - Wang CY AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. AD - Department of Pathophysiology, Medical College, University of South China, Hengyang, 421001, Hunan, People's Republic of China. FAU - Zhang, Ping AU - Zhang P AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. AD - Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China. FAU - Tang, Xiao-Qing AU - Tang XQ AD - Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, 28 West Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. tangxq-usc@qq.com. AD - Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China. tangxq-usc@qq.com. AD - Department of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China. tangxq-usc@qq.com. LA - eng GR - 81371485/Natural Science Foundation of China/International GR - 81471310/Natural Science Foundation of China/International GR - A2017020/Major Research Topics of the Healthand Family Planning Commission of Hunan province/International GR - 17A187/Key Projects of the Education Department of Hunan province/International GR - CX2017B545/Hunan Provincial Innovation Foundation for Postgraduate/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180427 PL - United States TA - Neuromolecular Med JT - Neuromolecular medicine JID - 101135365 RN - 0 (Antidepressive Agents) RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Indole Alkaloids) RN - 0 (Nerve Tissue Proteins) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Ntrk2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) RN - YY9FVM7NSN (Hydrogen Sulfide) MH - Animals MH - Antidepressive Agents/*pharmacology MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*physiology MH - Carbazoles/*pharmacology MH - Endoplasmic Reticulum Stress/*drug effects MH - Exploratory Behavior/drug effects MH - Gene Expression Regulation/drug effects MH - Hippocampus/*drug effects MH - Hydrogen Sulfide/*pharmacology MH - Indole Alkaloids/*pharmacology MH - Male MH - Motor Activity/drug effects MH - Nerve Tissue Proteins/biosynthesis/genetics/physiology MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/antagonists & inhibitors/*physiology MH - Signal Transduction/drug effects MH - Stress, Psychological/drug therapy/*metabolism MH - Swimming OTO - NOTNLM OT - BDNF/TrkB pathway OT - Chronic unpredictable mild stress OT - Depression OT - Endoplasmic reticulum stress OT - Hydrogen sulfide EDAT- 2018/04/29 06:00 MHDA- 2019/08/01 06:00 CRDT- 2018/04/29 06:00 PHST- 2017/08/15 00:00 [received] PHST- 2018/04/04 00:00 [accepted] PHST- 2018/04/29 06:00 [pubmed] PHST- 2019/08/01 06:00 [medline] PHST- 2018/04/29 06:00 [entrez] AID - 10.1007/s12017-018-8489-7 [pii] AID - 10.1007/s12017-018-8489-7 [doi] PST - ppublish SO - Neuromolecular Med. 2018 Jun;20(2):252-261. doi: 10.1007/s12017-018-8489-7. Epub 2018 Apr 27.