Division of Nuclear Medicine, Leuven University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium.
J Nucl Med. 2010 Sep;51(9):1413-7. doi: 10.2967/jnumed.110.077156. Epub 2010 Aug 18.
The type 1 cannabinoid receptor (CB1) is a crucial modulator of synaptic transmission in the brain. Animal and postmortem human data suggest that mutant huntingtin represses CB1 transcription. Our aim was to measure CB1 levels in the brains of Huntington disease (HD) patients in vivo.
Twenty symptomatic HD patients and 14 healthy controls underwent PET with the novel CB1 ligand N-[2-(3-cyano-phenyl)-3-(4-(2-(18)F-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide.
We observed a profound decrease of CB1 availability throughout the gray matter of the cerebrum, cerebellum, and brain stem in HD patients, even in early disease stages. Disease burden ([number of CAG repeats in the HTT gene - 35.5] x age) was inversely correlated with CB1 availability in the prefrontal and premotor cortex.
The profound early and widespread reduction of CB1 availability in vivo is consistent with the hypothesis that mutant huntingtin represses CB1 transcription. This is the first, to our knowledge, in vivo demonstration of disturbance of the endocannabinoid system in a human neurologic disease.
在体内测量亨廷顿病（HD）患者的 CB1 水平。
20 名有症状的 HD 患者和 14 名健康对照者接受了新型 CB1 配体 N-[2-(3-氰基-苯基)-3-(4-(2-(18)F-氟乙氧基)苯基)-1-甲基丙基]-2-(5-甲基-2-吡啶氧基)-2-甲基丙酰胺的 PET 检查。
我们观察到 HD 患者大脑灰质、小脑和脑干的 CB1 可用性明显降低，即使在疾病早期也是如此。疾病负担（HTT 基因中的[CAG 重复数-35.5]x 年龄）与前额叶和运动前皮质的 CB1 可用性呈负相关。
体内 CB1 可用性的明显早期和广泛降低与突变 huntingtin 抑制 CB1 转录的假说一致。这是我们所知的第一个在人类神经疾病中体内显示内源性大麻素系统紊乱的证据。
