Affiliated Nanhua Hospital, Department of Neurology, Hengyang Medical School, University of South China, Hengyang, China.
Key Laboratory for Cognitive Disorders and Neurodegenerative Diseases, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang, China.
Pharmacol Biochem Behav. 2024 Jan;234:173677. doi: 10.1016/j.pbb.2023.173677. Epub 2023 Nov 13.
Depression is a highly prevalent comorbidity arising in patients with Parkinson's disease (PD). However, depression in patients with PD is poorly treated. Hydrogen sulfide (HS), a neuromodulator, has the potential to relieve depression.
To investigate whether HS attenuates depression-like behaviours in a rat model of PD and examine the underlying mechanisms.
We utilised rotenone to develop a PD model with subcutaneous injections in the dorsal cervical region of Sprague-Dawley rats. The depression-like behaviours in the rotenone-induced PD model rats were assessed through forced swimming, tail suspension, open field, novelty-suppressed feeding, and elevated plus-maze tests. The expression of postsynaptic density protein-95 and synapsin-1, related to synaptic plasticity, was detected using Western blot in the hippocampus. The hippocampal ultrastructure, including the synaptic density, length of the synaptic active zone, postsynaptic density thickness, and synaptic gap width, was detected using transmission electron microscopy.
We proved that sodium hydrosulfide (NaHS; a donor of HS) significantly attenuated the depression-like behaviours and disorders of hippocampal synaptic plasticity in rotenone-induced PD rats. Furthermore, inhibition of the hippocampal Warburg effect by 2-deoxyglucose abolished NaHS-enhanced hippocampal synaptic plasticity and reversed NaHS-attenuated depression-like behaviours in the rotenone-induced PD rats.
HS attenuates PD-associated depression by improving the hippocampal synaptic plasticity in a hippocampal Warburg effect-dependent manner.
抑郁症是帕金森病（PD）患者中常见的共病。然而，PD 患者的抑郁症治疗效果不佳。硫化氢（HS）作为一种神经调节剂，具有缓解抑郁的潜力。
研究 HS 是否能减轻 PD 大鼠模型中的抑郁样行为，并探讨其潜在机制。
我们采用鱼藤酮对 Sprague-Dawley 大鼠进行背部颈部皮下注射，建立 PD 模型。通过强迫游泳、悬尾、旷场、新异抑制进食和高架十字迷宫试验评估鱼藤酮诱导的 PD 模型大鼠的抑郁样行为。采用 Western blot 检测海马中与突触可塑性相关的突触后密度蛋白-95 和突触小体-1 的表达。采用透射电子显微镜检测海马的超微结构，包括突触密度、突触活性区长度、突触后密度厚度和突触间隙宽度。
我们证明了氢硫化钠（HS 的供体）显著减轻了鱼藤酮诱导的 PD 大鼠的抑郁样行为和海马突触可塑性障碍。此外，通过 2-脱氧葡萄糖抑制海马的沃伯格效应，消除了 NaHS 增强的海马突触可塑性，并逆转了 NaHS 减轻的鱼藤酮诱导的 PD 大鼠的抑郁样行为。
HS 通过依赖于海马沃伯格效应的方式改善海马突触可塑性，从而减轻 PD 相关的抑郁。
