Thalamic noradrenaline in Parkinson's disease: deficits suggest role in motor and non-motor symptoms.
Thalamic noradrenaline in Parkinson's disease: deficits suggest role in motor and non-motor symptoms.
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DOI：
10.1002/mds.25109
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Hornykiewicz O
中科院分区：
文献类型：
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作者：
Pifl C;Kish SJ;Hornykiewicz O
丘脑在皮质-基底神经节-皮质回路中占有举足轻重的地位。在帕金森氏症中，丘脑表现出病理性的神经元放电模式，最重要的是增加的爆发和振荡活动，这被认为扰乱了基底节区冲动流向皮层的忠实转移。在实验中丘脑去甲肾上腺素减少的动物中出现类似的异常丘脑放电模式；相反，添加到丘脑神经元制剂中，去甲肾上腺素表现出明显的抗振荡和抗破裂活性。我们的研究是基于去甲肾上腺素和丘脑神经元放电质量之间的这种实验建立的联系。我们分析了9名帕金森病患者和8名对照者的14个丘脑核的所有功能相关区域，并使用高压液相色谱电化学检测测量去甲肾上腺素。在帕金森氏病中，去甲肾上腺素在所有运动核（颞叶和小脑）丘脑（腹前核：-86%，p=0.0011；腹外侧口核：-87%，p=0.0010；腹外侧尾核：-89%，p=0.0014）中显著减少：在其他丘脑区域，包括联合区、边缘区和层间区，也发现了显著的去甲肾上腺素损失，从68%到91%不等；主要感觉区只受到轻微影响。丘脑显著的去甲肾上腺素能失分化揭示了帕金森病整体病理生理中有策略定位的去甲肾上腺素能成分，提示其在运动和非运动症状发生的复杂机制中起作用。因此，我们的研究显著有助于了解帕金森病的肠外非多巴胺能机制，并与该疾病的治疗直接相关。
The thalamus occupies a pivotal position within the cortico-basal ganglia-cortical circuits. In Parkinson's disease, the thalamus exhibits pathological neuronal discharge patterns, foremost increased bursting and oscillatory activity, which are thought to perturb the faithful transfer of basal ganglia impulse flow to the cortex. Analogous abnormal thalamic discharge patterns develop in animals with experimentally reduced thalamic noradrenaline; conversely, added to thalamic neuronal preparations, noradrenaline exhibits marked anti-oscillatory and anti-bursting activity. Our study is based on this experimentally established link between noradrenaline and the quality of thalamic neuronal discharges. We analysed fourteen thalamic nuclei from all functionally relevant territories of nine patients with Parkinson's disease and eight controls and measured noradrenaline with high pressure liquid chromatography with electrochemical detection. In Parkinson's disease, noradrenaline was profoundly reduced in all nuclei of the motor (pallidonigral and cerebellar) thalamus (ventroanterior: -86%, p=0.0011; ventrolateral oral: -87%, p=0.0010; ventrolateral caudal: -89%, p=0.0014): Also marked noradrenaline losses, ranging from 68% to 91% of controls, were found in other thalamic territories, including associative, limbic and intralaminar regions; the primary sensory regions were only mildly affected. The marked noradrenergic deafferentiation of the thalamus discloses a strategically located noradrenergic component in the overall pathophysiology of the Parkinson's disease, suggesting a role in the complex mechanisms involved with the genesis of the motor and non-motor symptoms. Our study thus significantly contributes to the knowledge of the extrastriatal non-dopaminergic mechanisms of Parkinson's disease with direct relevance to treatment of this disorder.