BDNF/TrkB Pathway Mediates The Antidepressant-Like Effect Of Hydrogen Sulfide On Stz-Induced Diabetic Rats

[Background and Objective]Our team found that hydrogen sulfide(H2S) can reduce the depressive-like behaviors in diabetic rats and upregulate the expression of brain-derived neurotrophic factor(BDNF) in hippocampus of diabetic rats. Thus, the present work was to investigate whether BDNF/TrkB pathway mediates H2S-improved depressive-like behavior in diabetic rats by exploring the effects of K252 a, an inhibitor of BDNF/TrkB pathway, on H2S-caused suppression in depressive-like behavior in diabetic rats. [Methods]Forced swimming test, tail suspension test, novelty suppressed feeding test and elevated plus-maze test were used to observe the depressive-like behaviors. The levels of malondialdehyde(MDA), glutathione(GSH), and superoxide dismutase(SOD) in the hippocampus were assayed by enzyme-linked inmunosorbent assay(ELISA). Western blot was used to evaluate the expressions of Bax, Bcl-2, Bip, Chop, P62 and Beclin-1. HE staining, Tunnel staining and electron microscope are also used to observe the injury of hippocampal neurons. [Results]1. K252 a, the inhibitor of BDNF/TrkB pathway, reversed H2S-induced decrease in the latency to the first bite of food in the NSFT and the duration of immobility in the TST and the FST of diabetic rats as well as increases in the duration of climbing in FST and the time spent in open arms in EPM test of diabetic rats.2. K252 a abolished H2S-induced suppression in oxidative stress, apoptosis, and endoplasmic reticulum stress as well as increase in the level of autophagy in the hippocampus of diabetic rats. [Conclusion]BDNF/TrkB pathway mediates H2S-improved the depressive-like behavior in diabetic rats, by which protects against hippocampal damages.