Loss of response to levodopa in Parkinson's disease and co-occurrence with dementia:: role of D3 and not D2 receptors
Loss of response to levodopa in Parkinson's disease and co-occurrence with dementia:: role of D3 and not D2 receptors
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DOI：
10.1016/s0006-8993(02)03396-6
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发表时间：
2002-11-15
期刊：
影响因子：
2.9
通讯作者：
Adler, CH
中科院分区：
文献类型：
--
作者：
Joyce, JN;Ryoo, HL;Adler, CH
以前的数据表明帕金森病(PD)患者对左旋多巴的反应丧失与痴呆的共同发生之间存在关系，但尚未探讨多巴胺系统变化的作用。我们测量了既往有或没有对多巴胺能药物失去临床反应和/或有痴呆附加诊断的帕金森病患者死后纹状体DA丢失的程度和纹状体DA D-2和D-3受体的变化。对帕金森病和痴呆症进行临床评估和回顾，并进行神经病理学诊断。所有帕金森病患者(+/-痴呆)，无论对多巴胺能药物的反应如何，都表现出显著和相似的纹状体酪氨酸羟化酶免疫细胞化学和DA转运体结合丢失，以及腹侧中脑酪氨酸羟化酶免疫反应神经元和脑源性神经营养免疫反应神经元的丢失。所有PD患者(+/-痴呆)的纹状体D-2受体浓度均轻度升高，无论他们是否继续对多巴胺能药物有反应。相反，D-3受体浓度的丧失与多巴胺能药物的反应丧失相关，与痴呆症的存在与否无关。对多巴胺能药物的维持反应与D-3受体的升高有关。帕金森病痴呆与多巴胺能药物反应丧失高度相关，也与D-3受体减少相关。伏隔核、尾侧纹状体和苍白球D-3受体浓度变化最大。因此，与D-2受体的改变相比，多巴胺D-3受体的丢失可能是导致多巴胺能药物反应丧失的更重要的因素。(C)2002 Elsevier Science B.V.保留所有权利。
Previous data suggest a relationship between the loss of response to levodopa in Parkinson's disease (PD) patients with the co-occurrence of dementia, but the role of alterations in the dopamine system has not been explored. We measured the extent of striatal DA loss and changes in striatal DA D-2 and D-3 receptors in postmortem striatum of PD patients who historically had or had not lost their clinical response to dopaminergic drugs and/or had an additional diagnosis of dementia. Clinical evaluation and retrospective chart reviews for PD and dementia, and neuropathological diagnoses were obtained. All PD cases (+/-dementia), regardless of response to dopaminergic drugs, exhibited a significant and similar degree and pattern of loss of tyrosine hydroxylase immunocytochemistry and DA transporter binding in striatum, and loss of tyrosine hydroxylase-immunoreactive neurons and brain-derived neurotrophic-immunoreactive neurons from the ventral midbrain. D-2 receptor concentrations were modestly elevated in the rostral striatum of all the PD cases (+/-dementia), whether or not they continued to respond to dopaminergic drugs. In contrast, loss of D-3 receptor concentration correlated with loss of response to dopaminergic drugs, independent of the presence or absence of dementia. A maintained response to dopaminergic drugs correlated with an elevation of D-3 receptors. Dementia with PD was highly correlated with a loss of response to dopaminergic drugs, and was also correlated with reduced D-3 receptors. The alterations in D-3 receptor concentrations were greatest in the nucleus accumbens, caudal striatum, and globus pallidus. Thus, loss of dopamine D-3 receptors may be a more important contributing factor to a loss of response to dopaminergic drugs than changes in the D-2 receptor. (C) 2002 Elsevier Science B.V. All rights reserved.