Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease.
Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease.
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DOI：
10.1016/j.brs.2017.08.008
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发表时间：
2017-11
影响因子：
7.7
通讯作者：
Boger HA
中科院分区：
文献类型：
--
作者：
Farrand AQ;Helke KL;Gregory RA;Gooz M;Hinson VK;Boger HA
帕金森病（PD）是一种进行性神经退行性疾病，没有疾病修饰疗法，对症治疗往往受到使人衰弱的副作用的限制。在PD中，蓝斑去甲肾上腺素能（LC-NE）神经元先于黑质多巴胺能（SN-DA）神经元退化。迷走神经刺激（VNS）激活LC神经元，并减少促炎标志物，从而改善LC靶点，使其成为潜在的PD治疗剂。评估VNS在PD模型中的治疗潜力。为了模拟PD变性的进展，大鼠接受全身注射去甲肾上腺素能神经毒素DSP-4，一周后通过双侧纹状体内注射多巴胺能神经毒素6-羟基多巴胺。此时，一部分大鼠也植入了迷走神经袖带。11天后，大鼠接受精确的VNS方案，每天两次，持续10天，并在每个下午测量运动。最后一次刺激后立即处死大鼠，并将左侧背侧纹状体、双侧SN和LC切片用于单胺能神经元（酪氨酸羟化酶，TH）、α-突触核蛋白、星形胶质细胞（GFAP）和小胶质细胞（Iba-1）的免疫组织化学检测。迷走神经刺激可明显增加损伤大鼠的运动能力。VNS还导致纹状体、SN和LC中TH的表达增加; SN α-突触核蛋白表达减少;以及损伤大鼠SN和LC中胶质细胞标记物的表达减少。此外，VNS后盐水处理的大鼠具有较高的LC TH和较低的SN Iba-1。我们的发现增加运动，对LC-NE和SN-DA神经元的有益作用，SN TH阳性神经元中α-突触核蛋白密度降低，以及神经炎症表明VNS具有作为新型PD治疗剂的潜力。
Parkinson’s disease (PD) is a progressive, neurodegenerative disorder with no disease-modifying therapies, and symptomatic treatments are often limited by debilitating side effects. In PD, locus coeruleus noradrenergic (LC-NE) neurons degenerate prior to substantia nigra dopaminergic (SN-DA) neurons. Vagus nerve stimulation (VNS) activates LC neurons, and decreases pro-inflammatory markers, allowing improvement of LC targets, making it a potential PD therapeutic. To assess therapeutic potential of VNS in a PD model. To mimic the progression of PD degeneration, rats received a systemic injection of noradrenergic neurotoxin DSP-4, followed one week later by bilateral intrastriatal injection of dopaminergic neurotoxin 6-hydroxydopamine. At this time, a subset of rats also had vagus cuffs implanted. After eleven days, rats received a precise VNS regimen twice a day for ten days, and locomotion was measured during each afternoon session. Immediately following final stimulation, rats were euthanized, and left dorsal striatum, bilateral SN and LC were sectioned for immunohistochemical detection of monoaminergic neurons (tyrosine hydroxylase, TH), α-synuclein, astrocytes (GFAP) and microglia (Iba-1). VNS significantly increased locomotion of lesioned rats. VNS also resulted in increased expression of TH in striatum, SN, and LC; decreased SN α-synuclein expression; and decreased expression of glial markers in the SN and LC of lesioned rats. Additionally, saline-treated rats after VNS, had higher LC TH and lower SN Iba-1. Our findings of increased locomotion, beneficial effects on LC-NE and SN-DA neurons, decreased α-synuclein density in SN TH-positive neurons, and neuroinflammation suggest VNS has potential as a novel PD therapeutic.
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影响因子：
10.6
作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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