ELEVATED CSF DYNORPHIN-A [1-8] IN TOURETTES SYNDROME
ELEVATED CSF DYNORPHIN-A [1-8] IN TOURETTES SYNDROME
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DOI：
10.1016/0024-3205(88)90575-9
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发表时间：
1988-01-01
期刊：
影响因子：
6.1
通讯作者：
COHEN, DJ
中科院分区：
文献类型：
--
作者：
LECKMAN, JF;RIDDLE, MA;COHEN, DJ
最近的一项神经病理学研究报告了一例严重抽动症S综合征(Tourette‘Gilles de la Tourette，TS)患者脑内纹状体-苍白球纤维强啡肽A免疫反应性降低。这一观察结果与强啡肽的神经解剖分布及其广泛的运动和行为效应相结合，导致人们猜测它在TS的病理生物学中所起的作用。我们报告了7名20至45岁的TS患者脑脊液中强啡肽A[1-8]浓度升高的情况。在这些患者中，脑脊液强啡肽的增加与强迫症的严重程度有关，但与抽动的严重程度无关。尽管脑脊液研究缺乏必要的精确度来解决特定中枢神经系统选择性参与的问题，这些发现表明内源性阿片类药物参与了TS和相关疾病的病理生物学。抽动症S综合征(TS)是一种儿童期起病的慢性神经精神障碍，以多种运动和语音症状为特征，严重程度起伏不定，并伴有包括某些形式的强迫症在内的一系列行为问题(1)。曾经被认为是一种罕见的疾病，现在估计TS的患病率为每1000名男孩中有1例，每10,000名女孩中有1例，而且很可能在相当大比例的人口中出现较轻微的综合征变种。虽然TS的病因尚不清楚，但TS在家族内的垂直传播遵循与常染色体显性遗传形式一致的模式(3，4)。神经生物学和药理学数据表明，中枢单胺和神经肽能系统参与了TS的病理生理过程，基底节结构仍然是TS和相关疾病的主要神经解剖学来源(1)。内源性阿片类物质，包括强啡肽和甲硫氨酸脑啡肽，集中在基底节的结构(5)，已知与中枢多巴胺能神经元(6，7)相互作用，并可能在运动功能的控制中发挥重要作用(8)。尸检脑研究直接表明阿片类药物与帕金森氏病、S病(9例)、亨廷顿S病(10例)以及最近的TS(11例)的病理生理学有关。Haber等人的神经病理学研究(11)报道了一例严重TS患者脑内投射到苍白球的纹状体纤维中强啡肽A[1-17]免疫反应性降低。这一观察结果与强啡肽的神经解剖分布及其广泛的运动和行为效应相结合，导致人们猜测它在TS的病理生物学中所起的作用。支持内源性阿片类药物作用的其他证据来自关于阿片类拮抗剂在TS患者治疗中的戏剧性作用的报道，但文献很少(12，13)。
A recent neuropathological study has reported decreased levels of dynorphin A immunoreactivity in striato-pallidal fibers in the brain of a patient with severe Gilles de la Tourette''s syndrome (TS). This observation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS. We report on the presence of elevated concentrations of dynorphin A [1-8] in the CSF of 7 TS patients, aged 20 to 45 years. The increase in CSF dynorphin was found to be associated with the severity of the obsessive compulsive symptoms but not with tic severity in these patients. Although CSF studies lack the precision necessary to address questions of selective involvement of neuronal systems in specific CNS locations, these findings suggest that endogenous opioids are involved in the pathobiology of TS and related disorders. Tourette''s syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset that is characterized by multiple motor and phonic tics that wax and wane in severity and an array of behavioral problems including some forms of obsessive compulsive disorder (COS) (1). Once thought to be a rare condition, the prevalence of TS is now estimated to be one case per 1,000 boys and one case per 10,000 girls, and milder variants of the syndrome are likely to occur in a sizeable percentage of the population (2). Although the etiology of TS remains unknown, the vertical transmission of TS within families follows a pattern consistent with an autosomal dominant form of inheritance (3,4). Neurobiologic and pharmacological data have implicated central monoaminergic and neuropeptidergic systems in the pathophysiology of TS, and basal ganglia structures remain the prime candidates as the neuroanatomical origin for TS and related conditions (1). Endogenous opioids, including dynorphin and met-enkephalin are concentrated in structures of the basal ganglia (5), are known to interact with central dopaminergic neurons (6,7), and may play an important role in the control of motor functions (8). Post-mortem brain studies have directly implicated opioids in the pathophysiology of Parkinson''s disease (9), Huntington''s disease (10), and most recently in TS (11). The neuropathological study of Haber et al. (11) reported decreaed levels of dynorphin A [1-17] immunoreactivity in striatal fibers projecting to the globus pallidus in the brain of a patient with severe TS. This observation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS. Additional evidence supporting the role of endogenous opioids comes from reports of dramatic, but poorly documented, effects of opiate antagonists in the treatment of TS patients (12,13).