Parkinson's disease (PD) is a prevalent neurodegenerative disease and approximately one third of patients with PD are estimated to experience depression. Paraquat (PQ) is the most widely used herbicide worldwide and PQ exposure is reported to induce PD with depression. However, the specific brain region and neural networks underlying the etiology of depression in PD, especially in the PQ-induced model, have not yet been elucidated. Here, we report that the VGluT2-positive glutamatergic neurons in the paraventricular thalamic nucleus (PVT) promote depression in the PQ-induced PD mouse model. Our results show that PVT neurons are activated by PQ and their activation increases the susceptibility to depression in PD mice. Conversely, inhibition of PVT neurons reversed the depressive-behavioral changes induced by PQ. Similar to the effects of intervention the soma of PVT neurons, stimulation of their projections into the central amygdaloid nucleus (CeA) also strongly influenced depression in PD mice. PQ induced malfunctioning of the glutamate system and changes in the dendritic and synaptic morphology in the CeA through its role on PVT neuronal activation. In summary, our results demonstrate that PVT neurons are key neuronal subtypes for depression in PQ-induced PD and promote depression processes through the PVT-CeA pathway.

中文翻译：

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室旁丘脑核中的 VGluT2 神经元亚型调节百草枯诱发的帕金森病的抑郁症


帕金森病 (PD) 是一种常见的神经退行性疾病，估计大约三分之一的帕金森病患者患有抑郁症。百草枯 (PQ) 是全世界使用最广泛的除草剂，据报道接触 PQ 会诱发 PD 抑郁症。然而，PD（尤其是 PQ 诱导模型）抑郁症病因的特定大脑区域和神经网络尚未阐明。在这里，我们报道了室旁丘脑核（PVT）中的 VGluT2 阳性谷氨酸能神经元在 PQ 诱导的 PD 小鼠模型中促进抑郁。我们的结果表明，PVT 神经元被 PQ 激活，并且它们的激活增加了 PD 小鼠对抑郁的易感性。相反，抑制 PVT 神经元可逆转 PQ 引起的抑郁行为变化。与干预 PVT 神经元体的效果类似，刺激它们向中央杏仁核 (CeA) 的投射也强烈影响 PD 小鼠的抑郁症。 PQ 通过其对 PVT 神经元激活的作用，诱导谷氨酸系统功能障碍以及 CeA 树突和突触形态的变化。总之，我们的结果表明，PVT 神经元是 PQ 诱导的 PD 中抑郁的关键神经元亚型，并通过 PVT-CeA 途径促进抑郁过程。