Schmaljohann Jörn, Gündisch Daniela, Minnerop Martina, Bucerius Jan, Joe Alexius, Reinhardt Michael, Guhlke Stefan, Biersack Hans-Jürgen, Wüllner Ullrich
Department of Neurology, University of Bonn, Germany.
Nucl Med Biol. 2006 Apr;33(3):305-9. doi: 10.1016/j.nucmedbio.2005.12.012. Epub 2006 Mar 9.
Nicotinic acetylcholine receptors (nAChR) are involved in many physiological functions and appear to be affected in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease (PD). Here, we describe the in vitro evaluation of nAChRs in PD with 2-[18F]F-A85380, a ligand with high affinity to the beta2 nAChR subunit. Autoradiography with 2-[18F]F-A85380 in untreated rat brain corresponded to the known distribution of alpha4beta2 nAChRs with high uptake in the thalamus, moderate uptake in the striatum and cortex and low uptake in the cerebellum (47%, 43% and 19% of the thalamus, respectively). The localization of alpha4beta2 nAChRs in the striatum was investigated in rodents with unilateral lesion of the substantia nigra. 2-[18F]F-A85380 binding was significantly reduced in the striatum ipsilateral to the lesion side (to 64% of the contralateral side), indicating that a fraction of alpha4beta2 nAChRs is located on dopaminergic terminals, whereas another fraction resides on striatal interneurons or cortical afferents. Similarly, in human brain sections of PD patients, 2-[18F]F-A85380 uptake was significantly reduced not only in the caudate and putamen but also in the thalamus (approximately 30% of the binding of control brain in all three regions); within the striatum, nAChRs in the putamen were significantly more severely affected as in the caudate. The observed pattern of alpha4beta2* nAChR loss demonstrates the potential of 2-[18F]F-A85380 for further investigations of this positron emission tomography ligand for in vivo studies of alpha4beta2* nAChRs in PD.
烟碱型乙酰胆碱受体（nAChR）参与多种生理功能，且在阿尔茨海默病和帕金森病（PD）等神经退行性疾病中似乎会受到影响。在此，我们描述了用2-[18F]F-A85380对PD患者的nAChR进行体外评估，2-[18F]F-A85380是一种对β2 nAChR亚基具有高亲和力的配体。在未处理的大鼠脑中用2-[18F]F-A85380进行放射自显影，结果与已知的α4β2 nAChR分布相符，丘脑摄取量高，纹状体和皮质摄取量中等，小脑摄取量低（分别为丘脑摄取量的47%、43%和19%）。在黑质单侧损伤的啮齿动物中研究了α4β2 nAChR在纹状体中的定位。损伤侧同侧纹状体中2-[18F]F-A85380的结合显著降低（降至对侧的64%），表明一部分α4β2 nAChR位于多巴胺能终末，而另一部分位于纹状体中间神经元或皮质传入神经上。同样，在PD患者的人脑切片中，2-[18F]F-A85380的摄取不仅在尾状核和壳核中显著降低，在丘脑中也显著降低（在所有三个区域中约为对照脑结合量的30%）；在纹状体内，壳核中的nAChR比尾状核中的受影响更严重。观察到的α4β2* nAChR丢失模式表明，2-[18F]F-A85380有潜力用于进一步研究这种正电子发射断层扫描配体，以在体内研究PD患者的α4β2* nAChR。
