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27.04.2018 | Original Paper

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

verfasst von: 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

Erschienen in: NeuroMolecular Medicine | Ausgabe 2/2018

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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.

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Titel: BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress
verfasst von: 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
Publikationsdatum: 27.04.2018
Verlag: Springer US
Erschienen in: NeuroMolecular Medicine / Ausgabe 2/2018
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-018-8489-7

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

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