Manipulation of vocal communication and anxiety through pharmacologic modulation of norepinephrine in the Pink1-/- rat model of Parkinson disease.
Manipulation of vocal communication and anxiety through pharmacologic modulation of norepinephrine in the Pink1-/- rat model of Parkinson disease.
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在帕金森病Pink 1-/-大鼠模型中通过去甲肾上腺素的药理学调节来操纵声音交流和焦虑。
DOI：
10.1016/j.bbr.2021.113642
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发表时间：
2022-02-10
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
发声障碍和焦虑是帕金森病(PD)常见的、共同发生的和相互作用的迹象，对生活质量有毁灭性的影响。两者都在疾病过程的早期表现出来。与帕金森病的标志性运动体征不同，两者对多巴胺替代疗法都没有足够的反应，这表明它们的疾病特异性机制至少部分是超多巴胺能的。由于去甲肾上腺素功能障碍也是帕金森病的一个决定性特征，特别是在疾病进展的早期，针对去甲肾上腺素的药物疗法正在试验中，用于治疗帕金森病患者的运动和非运动障碍。然而，评估去甲肾上腺素能手法对帕金森病患者焦虑和发声障碍的影响的研究很少。在这项临床前研究中，我们量化了去甲肾上腺素对PINK1−/−大鼠发声障碍和焦虑的影响，这是一种既表现发声障碍又表现焦虑的帕金森病翻译模型。对每只大鼠进行了两次超声波发声声学、焦虑行为和肢体运动活动测试：注射生理盐水后和注射三种药物后。我们假设去甲肾上腺素再摄取抑制剂(托莫西汀和瑞波西汀)和β受体拮抗剂(心得安)与生理盐水相比可以减少发声障碍和焦虑，而不影响自发运动能力。我们的结果表明，托莫西汀和瑞波西汀可以减少焦虑行为。托莫西汀还调节超声发声声学，包括增加发声强度，这在动物模型和帕金森病患者中几乎总是降低。心得安不影响焦虑或发声。药物状态不影响自发运动活动。这些研究证实了PINK1−/−帕金森病大鼠模型中发声障碍、焦虑和去甲肾上腺素能系统之间的关系。
Vocal deficits and anxiety are common, co-occurring, and interacting signs of Parkinson Disease (PD) that have a devastating impact on quality of life. Both manifest early in the disease process. Unlike hallmark motor signs of PD, neither respond adequately to dopamine replacement therapies, suggesting that their disease-specific mechanisms are at least partially extra-dopaminergic. Because noradrenergic dysfunction is also a defining feature of PD, especially early in the disease progression, drug therapies targeting norepinephrine are being trialed for treatment of motor and non-motor impairments in PD. Research assessing the effects of noradrenergic manipulation on anxiety and vocal impairment in PD, however, is sparse. In this pre-clinical study, we quantified the influence of pharmacologic manipulation of norepinephrine on vocal impairment and anxiety in Pink1−/− rats, a translational model of PD that demonstrates both vocal deficits and anxiety. Ultrasonic vocalization acoustics, anxiety behavior, and limb motor activity were tested twice for each rat: after injection of saline and after one of three drugs. We hypothesized that norepinephrine reuptake inhibitors (atomoxetine and reboxetine) and a β receptor antagonist (propranolol) would decrease vocal impairment and anxiety compared to saline, without affecting spontaneous motor activity. Our results demonstrated that atomoxetine and reboxetine decreased anxiety behavior. Atomoxetine also modulated ultrasonic vocalization acoustics, including an increase in vocal intensity, which is almost always reduced in animal models and patients with PD. Propranolol did not affect anxiety or vocalization. Drug condition did not influence spontaneous motor activity. These studies demonstrate relationships among vocal impairment, anxiety, and noradrenergic systems in the Pink1−/− rat model of PD.
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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：
1.7
作者：
Dannon, PN;Iancu, I;Grunhaus, L
通讯作者：
Grunhaus, L
DOI：
10.1044/jshr.1203.462
发表时间：
1969-01-01
期刊：
JOURNAL OF SPEECH AND HEARING RESEARCH
影响因子：
--
作者：
DARLEY, FL;ARONSON, AE;BROWN, JR
通讯作者：
BROWN, JR
影响因子：
3.4
作者：
Concha-Miranda, Miguel;Hartmann, Konstantin;Sanguinetti-Scheck, Juan, I
通讯作者：
Sanguinetti-Scheck, Juan, I
影响因子：
4.1
作者：
Bezard, Erwan;Fernagut, Pierre-Olivier
通讯作者：
Fernagut, Pierre-Olivier