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
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
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DOI：
10.1016/j.bbr.2021.113562
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发表时间：
2021-09
影响因子：
2.7
通讯作者：
San-Qiao Yang;Yi-Yun Tang;Dan Zeng;Qing Tian;Hai-jun Wei;Chun-yan Wang;Ping Zhang;Yong-jun Chen-Yong-jun-Che
中科院分区：
文献类型：
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作者：
San-Qiao Yang;Yi-Yun Tang;Dan Zeng;Qing Tian;Hai-jun Wei;Chun-yan Wang;Ping Zhang;Yong-jun Chen-Yong-jun-Che
我们之前的研究表明，β2-微球蛋白（β2m）是一种系统性的促衰老因子，可诱导抑郁样行为。硫化氢（H2S）被认为是治疗抑郁症的潜在靶点。本研究旨在探讨H2S是否能拮抗β2m诱导的抑郁样行为及其潜在机制。方法采用新颖性抑制进食测验（NSFT）、悬尾测验（TST）、强迫游泳测验（FST）和开阔场地测验（OFT）检测抑郁样行为。western blotting检测warburg相关蛋白（己糖激酶II （HK II）、丙酮酸激酶M2 （PKM2）、乳酸脱氢酶A （LDHA）、丙酮酸脱氢酶（PDH）、丙酮酸脱氢酶激酶1(PDK1)）和突触可塑性相关蛋白（突触后密度蛋白95 （PSD95）、突触融合蛋白1(SYN1)）的表达。结果通过NSFT、TST、FST和OFT检测，我们发现NaHS （H2S供体）对β2m暴露大鼠的抑郁样行为有一定的抑制作用。我们还通过β2m暴露大鼠海马PSD95和SYN1表达上调证明了NaHS增强了突触可塑性。此外，NaHS改善了β2m暴露大鼠海马的Warburg效应，表现为HK II、PKM2、LDHA和PDK1表达上调，PDH表达下调。结论h2s可抑制β2m诱导的抑郁样行为，其机制可能与通过增强海马Warburg效应改善海马突触可塑性有关。
BackgroundOur 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.MethodsThe 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.Resultwe 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.ConclusionH2S prevents β2m-induced depressive-like behaviors, which is involved in improvement of hippocampal synaptic plasticity as a result of enhancement of hippocampal Warburg effect.