Department of Communication Sciences and Disorders, University of Wisconsin-Madison, 1975 Willow Drive, Madison, WI, 53706, USA; Department of Surgery, Division of Otolaryngology-Head & Neck Surgery, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792-7375, USA.
Department of Surgery, Division of Otolaryngology-Head & Neck Surgery, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, 53792-7375, USA.
Behav Brain Res. 2021 Sep 24;414:113514. doi: 10.1016/j.bbr.2021.113514. Epub 2021 Aug 4.
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.
嗓音交流障碍和焦虑是帕金森病（PD）的共同且相互作用的迹象，它们很常见，但人们对其了解甚少，且治疗效果不佳。嗓音交流和焦虑均受去甲肾上腺素能系统的影响。鉴于这种共同的神经基础，并且考虑到去甲肾上腺素能功能障碍是 PD 的一个明确特征，因此对 PD 中嗓音障碍和焦虑与去甲肾上腺素能机制的联合研究可能会深入了解这些障碍的潜在疾病特异性原因。为了填补这一知识空白，我们评估了遗传早发性 PD （Pink1-/-）大鼠模型和野生型对照（WT）的嗓音障碍和焦虑行为与脑干去甲肾上腺素能标志物之间的关系。我们假设 1）Pink1-/-大鼠的脑干去甲肾上腺素能标志物会受到破坏，2）脑干去甲肾上腺素能标志物与嗓音声学变化和焦虑水平相关。大鼠在 4、8 和 12 个月大时接受超声发声和焦虑（高架十字迷宫）测试。在 12 个月时，通过免疫组织化学定量测定脑干去甲肾上腺素标志物。结果表明，Pink1-/-大鼠的嗓音障碍和焦虑增加，并且在这种 PD 模型中，焦虑增加与更大的嗓音缺陷相关。此外，包括蓝斑中的 TH 和α1肾上腺素能受体免疫反应性以及迷走神经核中的β1肾上腺素能受体免疫反应性在内的脑干去甲肾上腺素能标志物因基因型而异，并且与发声和焦虑行为相关。这些发现表明在 Pink1-/-大鼠 PD 模型中，嗓音障碍、焦虑和脑干去甲肾上腺素之间存在显著的统计学关系。
