Dipartimento di Fisiologia Umana, Università degli Studi di Milano, Milano, Italy.
BMC Neurol. 2011 Jul 21;11:88. doi: 10.1186/1471-2377-11-88.
Studies in animals suggest that the noradrenergic system arising from the locus coeruleus (LC) and dopaminergic pathways mutually influence each other. Little is known however, about the functional state of the LC in patients with Parkinson disease (PD).
We retrospectively reviewed clinical and imaging data of 94 subjects with PD at an early clinical stage (Hoehn and Yahr stage 1-2) who underwent single photon computed tomography imaging with FP-CIT ([¹²³I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane). FP-CIT binding values from the patients were compared with 15 healthy subjects: using both a voxel-based whole brain analysis and a volume of interest analysis of a priori defined brain regions.
Average FP-CIT binding in the putamen and caudate nucleus was significantly reduced in PD subjects (43% and 57% on average, respectively; p < 0.001). In contrast, subjects with PD showed an increased binding in the LC (166% on average; p < 0.001) in both analyses. LC-binding correlated negatively with striatal FP-CIT binding values (caudate: contralateral, ρ = -0.28, p < 0.01 and ipsilateral ρ = -0.26, p < 0.01; putamen: contralateral, ρ = -0.29, p < 0.01 and ipsilateral ρ = -0.29, p < 0.01).
These findings are consistent with an up-regulation of noradrenaline reuptake in the LC area of patients with early stage PD, compatible with enhanced noradrenaline release, and a compensating activity for degeneration of dopaminergic nigrostriatal projections.
动物研究表明,来自蓝斑核(LC)的去甲肾上腺素能系统和多巴胺能通路相互影响。然而,关于帕金森病(PD)患者 LC 的功能状态知之甚少。
我们回顾性分析了 94 例早期临床阶段(Hoehn 和 Yahr 1-2 期)PD 患者的临床和影像学数据,这些患者接受了 FP-CIT ([¹²³I] N-ω-氟丙基-2β-羧基-3β-(4-碘苯基)托烷)单光子计算机断层扫描成像。将患者的 FP-CIT 结合值与 15 名健康受试者进行比较:使用基于体素的全脑分析和预先定义的脑区的感兴趣区分析。
PD 患者纹状体和尾状核的平均 FP-CIT 结合显著降低(分别平均降低 43%和 57%;p<0.001)。相比之下,PD 患者 LC 的结合增加(平均增加 166%;p<0.001),两种分析均如此。LC 结合与纹状体 FP-CIT 结合值呈负相关(尾状核:对侧 ρ=-0.28,p<0.01;同侧 ρ=-0.26,p<0.01;壳核:对侧 ρ=-0.29,p<0.01;同侧 ρ=-0.29,p<0.01)。
这些发现与早期 PD 患者 LC 区域去甲肾上腺素再摄取增加一致,与增强的去甲肾上腺素释放和多巴胺能黑质纹状体投射变性的代偿活性相容。