Serotonin transporters in the midbrain of Parkinson's disease patients: a study with 123I-beta-CIT SPECT.
Serotonin transporters in the midbrain of Parkinson's disease patients: a study with 123I-beta-CIT SPECT.
复制标题
帕金森病患者中脑中的血清素转运蛋白：123I-β-CIT SPECT 的研究。
作者：
Sang Eun Kim;J. Choi;Y. Choe;Yong Choi;W. Lee
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在帕金森病(PD)中，神经病理学和生化研究都表明5-羟色胺(5-羟色胺[5-HT])神经元受到疾病过程的影响。用与多巴胺(DA)和5-羟色胺(5-HT)转运蛋白高亲和力结合的2beta-carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane(123I-β-CIT)对帕金森病患者SPECT检查中5-羟色胺转运体的完整性进行评估。
方法
45例相对早期(Hoehn-Yahr分期，平均2.0+/-0.7；范围1-3)的PD患者和7名年龄匹配的健康对照组在注射123I-β-CIT后24小时内用3头SPECT系统进行了15次扫描。在中脑，5-羟色胺转运体参数k(3)/k(4)由3种无创性方法估计：假平衡比法(R(PE))、面积比法(R(A))和一种改进的图解法(R(V))。用示踪剂注射后24 h的图像测量纹状体V(3)“，即DA转运体参数k(3)/k(4)，以小脑为参照区。
结果
对照组大鼠中脑(123)I-β-CIT活性在注射后91+/-21分钟达到峰值，然后缓慢洗出(1.1%/h+/-0.5%/h)。中脑的特异性摄取高峰出现在315+/-46min。帕金森病患者的中脑和小脑活动的时间模式与对照组无显著差异。中脑R(PE)、R(A)和R(V)在对照组和PD患者之间无显著差异，而纹状体V(3)“在所有患者中的双侧降低，比对照组低32%(P=0.002)，PD患者的中脑预后指标与纹状体V(3)”或运动或非运动症状评分均无显著相关性，包括Hoehn-Yahr分期和统一帕金森病评定量表评分。当单独分析7例PD抑郁患者的研究时，这些患者的中脑结局指标与对照组均无显著差异，也未与汉密尔顿抑郁量表评分相关。
结论
这些结果提示帕金森病患者DA和5-羟色胺转运体受到不同程度的影响，而中脑区的5-羟色胺转运体可能在帕金森病的相对早期阶段不受影响。或者，剩余神经元中的5-羟色胺转运体可能上调，从而将中脑5-羟色胺转运体密度提高到几乎正常的水平。
UNLABELLED
In Parkinson's disease (PD), both neuropathologic and biochemical studies suggest that serotonin (5-hydroxytryptamine [5-HT]) neurons are affected by the disease process. The integrity of 5-HT transporters was assessed in PD patients with SPECT using 2beta-carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane ((123)I-beta-CIT), which binds with high affinity to both dopamine (DA) and 5-HT transporters.
METHODS
Forty-five PD patients at relatively early stages (mean Hoehn-Yahr stage, 2.0 +/- 0.7; range, 1-3) and 7 age-matched healthy control subjects had 15 scans over a 24-h period after injection of (123)I-beta-CIT using a 3-head SPECT system. In the midbrain, the 5-HT transporter parameter k(3)/k(4) was estimated by 3 noninvasive methods: pseudoequilibrium ratio (R(PE)) method, area ratio (R(A)) method, and a modified graphic method that derives the ratio of ligand distribution volumes (R(V)). Striatal V(3)", the DA transporter parameter that is equivalent to k(3)/k(4), was measured using the images acquired at 24 h after tracer injection. All measures were derived using the cerebellum as the reference region.
RESULTS
In control subjects, the (123)I-beta-CIT activity in the midbrain reached a peak at 91 +/- 21 min after injection and then washed out at a slow rate (1.1%/h +/- 0.5%/h). The peak specific uptake in the midbrain occurred at 315 +/- 46 min. In PD patients, the temporal patterns of the midbrain and cerebellar activity were not significantly different from those in control subjects. None of midbrain R(PE), R(A), and R(V) was significantly different between control subjects and PD patients, whereas striatal V(3)" was bilaterally reduced in all patients, being 32% lower than that of the control subjects (P = 0.002). In PD patients, none of the midbrain outcome measures was significantly correlated with either striatal V(3)" or motor or nonmotor symptom ratings, including the Hoehn-Yahr stage and the Unified Parkinson's Disease Rating Scale scores. When the studies of 7 PD patients with depression were analyzed separately, none of the midbrain outcome measures in these patients either was different significantly from control values or correlated with the Hamilton Depression Rating Scale score.
CONCLUSION
These results suggest that DA and 5-HT transporters are differentially affected in PD, and 5-HT transporters in the midbrain region may not be affected in relatively early stages of PD. Alternatively, 5-HT transporters in the remaining neurons may be upregulated, thus raising the midbrain 5-HT transporter density to almost normal levels.
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DOI：
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发表时间：
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DOI：
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期刊：
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影响因子：
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影响因子：
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