Meyer P, Bohnen N I, Minoshima S, Koeppe R A, Wernette K, Kilbourn M R, Kuhl D E, Frey K A, Albin R L
Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, USA.
Neurology. 1999 Jul 22;53(2):371-4. doi: 10.1212/wnl.53.2.371.
Abnormal function of striatal dopaminergic synapses is suggested to underlie Tourette's syndrome (TS).
To determine dorsal striatal dopaminergic innervation in TS. Prior in vitro and in vivo studies of dopamine reuptake transporter binding sites suggest increased striatal dopaminergic innervation in TS.
We used in vivo measures of striatal vesicular monoamine transporter type-2 (VMAT2) binding to quantify striatal dopaminergic innervation in TS. Eight TS patients (mean age 30+/-9 years) and 22 age-comparable normal controls (age 34+/-8 years) underwent PET imaging with the VMAT2 ligand (+)-alpha-[11C]dihydrotetrabenazine (DTBZ). Compartmental modeling was used to quantify blood-to-brain ligand transport and VMAT2 binding site density from the tissue-to-plasma distribution volume (DV) during continuous (+)-alpha-[11C]DTBZ infusion. DTBZ DV in dorsal striatal regions was expressed relative to the occipital cortex to estimate relative specific VMAT2 binding (binding potential).
We found no significant differences in VMAT2 binding potential between patients and controls in the caudate nucleus, anterior putamen, or posterior putamen. There were no significant differences in striatal VMAT2 binding between patients with (n = 5) or without (n = 3) features of obsessive-compulsive disorder.
There is no evidence for increased binding to the VMAT2 in TS striatum and that dorsal striatal dopaminergic innervation density is normal in TS. The previously reported changes in dopamine transporter binding sites may reflect medication effect and/or altered synaptic activity or regulation of dopamine transporter expression in nigrostriatal neurons.
纹状体多巴胺能突触功能异常被认为是妥瑞氏症(TS)的潜在病因。
确定妥瑞氏症患者背侧纹状体的多巴胺能神经支配情况。先前的体外和体内多巴胺再摄取转运体结合位点研究表明,妥瑞氏症患者纹状体多巴胺能神经支配增加。
我们采用体内纹状体2型囊泡单胺转运体(VMAT2)结合测量法来量化妥瑞氏症患者纹状体的多巴胺能神经支配。8名妥瑞氏症患者(平均年龄30±9岁)和22名年龄匹配的正常对照者(年龄34±8岁)接受了用VMAT2配体(+)-α-[11C]二氢四苯嗪(DTBZ)进行的PET成像。在持续输注(+)-α-[11C]DTBZ期间,采用房室模型从组织与血浆分布容积(DV)量化血脑配体转运和VMAT2结合位点密度。背侧纹状体区域的DTBZ DV相对于枕叶皮质来表示,以估计相对特异性VMAT2结合(结合潜力)。
我们发现,在尾状核、前壳核或后壳核中,患者与对照者之间的VMAT2结合潜力没有显著差异。患有(n = 5)或未患有(n = 3)强迫症特征的患者之间,纹状体VMAT2结合没有显著差异。
没有证据表明妥瑞氏症患者纹状体中VMAT2的结合增加,且妥瑞氏症患者背侧纹状体多巴胺能神经支配密度正常。先前报道的多巴胺转运体结合位点变化可能反映了药物作用和/或黑质纹状体神经元中多巴胺转运体表达的突触活动或调节改变。