Quantification of brainstem norepinephrine relative to vocal impairment and anxiety in the Pink1-/- rat model of Parkinson disease.
Quantification of brainstem norepinephrine relative to vocal impairment and anxiety in the Pink1-/- rat model of Parkinson disease.
复制标题
在帕金森氏病的Pink1 - / - 大鼠模型中，脑干去甲肾上腺素相对于声带障碍和焦虑的定量。
DOI：
10.1016/j.bbr.2021.113514
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发表时间：
2021-09-24
影响因子：
2.7
通讯作者：
Ciucci MR
中科院分区：
文献类型：
--
作者：
Hoffmeister JD;Kelm-Nelson CA;Ciucci MR
声音沟通障碍和焦虑是帕金森病（PD）的共同发生和相互作用的体征，这些体征很常见，了解甚少，治疗不足。声音交流和焦虑都受到去甲肾上腺素能系统的影响。鉴于这种共同的神经基质，并考虑到去甲肾上腺素能功能障碍是PD的一个定义特征，PD中与去甲肾上腺素能机制相关的发声障碍和焦虑的串联调查可能会深入了解这些障碍的潜在疾病特异性原因。为了解决这一知识差距，我们在早发性PD（Pink 1-/-）和野生型对照（WT）的遗传大鼠模型中评估了与脑干去甲肾上腺素能标记物相关的发声障碍和焦虑行为。我们假设1）脑干去甲肾上腺素能标记物在Pink 1 −/−中会被破坏，2）脑干去甲肾上腺素能标记物与声音声学变化和焦虑水平相关。大鼠在4、8和12个月大时进行超声发声和焦虑（高架迷宫）测试。在12个月时，脑干去甲肾上腺素标记物进行定量免疫组织化学。结果表明，在Pink 1 −/−大鼠中，声音障碍和焦虑增加，并且在该PD模型中，焦虑增加与更大的声音缺陷相关。此外，脑干去甲肾上腺素能标记物包括蓝斑的TH和α1肾上腺素受体免疫反应性，以及迷走神经核的β1肾上腺素受体免疫反应性因基因型而异，并且与发声和焦虑行为相关。这些研究结果表明，在PD的Pink 1 −/−大鼠模型中，发声障碍、焦虑和脑干去甲肾上腺素之间存在统计学显著性关系。
Vocal communication impairment and anxiety are co-occurring and interacting signs of Parkinson Disease (PD) that are common, poorly understood, and under-treated. Both vocal communication and anxiety are influenced by the noradrenergic system. In light of this shared neural substrate and considering that noradrenergic dysfunction is a defining characteristic of PD, tandem investigation of vocal impairment and anxiety in PD relative to noradrenergic mechanisms is likely to yield insights into the underlying disease-specific causes of these impairments. In order to address this gap in knowledge, we assessed vocal impairment and anxiety behavior relative to brainstem noradrenergic markers in a genetic rat model of early-onset PD (Pink1−/−) and wild type controls (WT). We hypothesized that 1) brainstem noradrenergic markers would be disrupted in Pink1−/−, and 2) brainstem noradrenergic markers would be associated with vocal acoustic changes and anxiety level. Rats underwent testing of ultrasonic vocalization and anxiety (elevated plus maze) at 4, 8, and 12 months of age. At 12 months, brainstem norepinephrine markers were quantified with immunohistochemistry. Results demonstrated that vocal impairment and anxiety were increased in Pink1−/− rats, and increased anxiety was associated with greater vocal deficit in this model of PD. Further, brainstem noradrenergic markers including TH and α1 adrenoreceptor immunoreactivity in the locus coeruleus, and β1 adrenoreceptor immunoreactivity in vagal nuclei differed by genotype, and were associated with vocalization and anxiety behavior. These findings demonstrate statistically significant relationships among vocal impairment, anxiety, and brainstem norepinephrine in the Pink1−/− rat model of PD.
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影响因子：
8.6
作者：
Barone, Paolo;Antonini, Angelo;Del Dotto, Paolo
通讯作者：
Del Dotto, Paolo
影响因子：
2.6
作者：
Calleo, Jessica S.;Amspoker, Amber B.;Stanley, Melinda A.
通讯作者：
Stanley, Melinda A.
影响因子：
2.9
作者：
CASH, R;RUBERG, M;AGID, Y
通讯作者：
AGID, Y
DOI：
10.1093/ijnp/pyv057
发表时间：
2015-05-19
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Costa G;Morelli M;Simola N
通讯作者：
Simola N
DOI：
10.1044/2015_jslhr-s-14-0243
发表时间：
2015-08-01
影响因子：
2.6
作者：
Anand, Supraja;Stepp, Cara E.
通讯作者：
Stepp, Cara E.