Sodium hydrosulfide reverses β2-microglobulin-induced depressive-like behaviors of male Sprague-Dawley rats: Involving improvement of synaptic plasticity and enhancement of Warburg effect in hippocampus

Our previous works demonstrated that β2-microglobulin (β2m), a systemic pro-aging factor, induce depressive-like behaviors. Hydrogen sulfide (H2S) is identified as a potential target for treatment of depression. The aim of the present work is to explore whether H2S antagonizes β2m-induced depressive-like behaviors and the underlying mechanisms. The depressive-like behaviors were detected using the novelty suppressed feeding test (NSFT), tail suspension test (TST), forced swimming test (FST) and open field test (OFT). The expressions of Warburg-related proteins, including hexokinase II (HK II), pyruvate kinase M2 (PKM2), Lactate dehydrogenase A (LDHA), pyruvate dehydrogenase (PDH) and pyruvate dehydrogenase kinase 1(PDK1), and synaptic plasticity-related proteins, including postsynaptic density protein 95 (PSD95) and synaptophysin1 (SYN1), were determined by western blotting. we found that NaHS (the donor of H2S) attenuated the depressive-like behaviors in the β2m-exposed rats, as judged by NSFT, TST, FST, and OFT. We also demonstrated that NaHS enhanced the synaptic plasticity, as evidenced by the upregulations of PSD95 and SYN1 expressions in the hippocampus of β2m-exposed rats. Furthermore, NaHS improved the Warburg effect in the hippocampus of β2m-exposed rats, as evidenced by the upregulations of HK II, PKM2, LDHA and PDK1 expressions, and the downregulation of PDH expression. H2S prevents β2m-induced depressive-like behaviors, which is involved in improvement of hippocampal synaptic plasticity as a result of enhancement of hippocampal Warburg effect. •H2S attenuates β2m-induced depressive-like behaviour.•H2S improves synaptic plasticity in the hippocampus of β2m-exposed rat.•H2S enhances Warburg effect in the hippocampus of β2m-exposed rat.•H2S prevents β2m-induced depression via Warburg effect- synaptic plasticity axis.