Background

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.

Methods

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.

Result

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.

Conclusion

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.

中文翻译：

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硫氢化钠逆转β2-微球蛋白诱导的雄性Sprague-Dawley大鼠抑郁样行为：涉及提高海马突触可塑性和增强Warburg效应

背景

我们之前的工作表明，β2-微球蛋白 (β2m) 是一种全身性促衰老因子，可诱导抑郁样行为。硫化氢 (H ₂ S) 被确定为治疗抑郁症的潜在目标。本工作的目的是探索H ₂ S 是否拮抗β2m 诱导的抑郁样行为及其潜在机制。

方法

使用新奇抑制喂养试验（NSFT）、悬尾试验（TST）、强迫游泳试验（FST）和旷场试验（OFT）检测抑郁样行为。Warburg相关蛋白的表达，包括己糖激酶II（HK II）、丙酮酸激酶M2（PKM2）、乳酸脱氢酶A（LDHA）、丙酮酸脱氢酶（PDH）和丙酮酸脱氢酶激酶1（PDK1），以及突触可塑性相关蛋白, 包括突触后密度蛋白 95 (PSD95) 和突触素 1 (SYN1), 通过蛋白质印迹测定。

结果

根据 NSFT、TST、FST 和 OFT 的判断，我们发现 NaHS（H ₂ S 的供体）减弱了 β2m 暴露大鼠的抑郁样行为。我们还证明了 NaHS 增强了突触可塑性，正如β2m 暴露大鼠海马中 PSD95 和 SYN1 表达的上调所证明的那样。此外，NaHS 改善了暴露于 β2m 的大鼠海马中的 Warburg 效应，这可以通过 HK II、PKM2、LDHA 和 PDK1 表达的上调以及 PDH 表达的下调来证明。

结论

H ₂ S 可防止 β2m 诱导的抑郁样行为，这与海马 Warburg 效应增强导致海马突触可塑性的改善有关。