Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain
Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain
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DOI：
10.1006/nimg.2001.0939
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发表时间：
2001-12-01
期刊：
影响因子：
5.7
通讯作者：
Kerman, IA
中科院分区：
文献类型：
--
作者：
Biegon, A;Kerman, IA
大麻素受体已被表征并定位于包括人类在内的几个物种的脑中。用[H-3] CP 55，940作配体，用定量放射自显影法研究了人脑CB 1受体在出生前后的分布。正常胎儿脑（N = 8，胎龄14-24周）从自愿流产获得。从纽约市和以色列Jaffa的医学检验办公室获得正常（无药物和病理学）成人脑（N = 16，年龄18-78）。将脑冷冻储存在-70 ℃下，并在-15 ℃下切片（40 μ m）。将放射性配体（5 nM）与切片在室温下孵育3 h。将洗涤和干燥的切片与标准品一起暴露于氚敏感膜沿着7-28天，并使用NIH Image软件定量放射自显影图。在胎儿人脑中，早在妊娠14周就可以观察到低密度的THC可置换的区域特异性结合。受体密度随胎龄缓慢增加，但在妊娠中期（妊娠24周）未达到成人水平。此外，胎儿脑中的分布模式与成人模式明显不同。最显著的差异是在胎儿尾状核和壳核中的结合密度非常低。相比之下，苍白球内侧部在妊娠17-18周时具有几乎成人水平的大麻素受体。胎儿大脑中大麻素受体的相对较低和区域选择性的出现可以解释在子宫内暴露于大麻素的婴儿中观察到的出生后神经行为缺陷的相对温和和选择性的性质。(C)北京：科学出版社.
Cannabinoid receptors have been characterized and localized in the brain of several species, including human. The pre- and postnatal distribution of human brain CB1 receptors was investigated using quantitative autoradiography with [H-3]CP55,940 as a ligand. Normal fetal brains (N = 8, gestational age 14-24 weeks) were obtained from voluntary abortions. Normal (drug and pathology free) adult human brains (N = 16, age 18-78) were obtained from the medical examiner's offices in New York City and Jaffa, Israel. Brains were stored frozen at -70 degreesC and sectioned (40 mum) at -15 degreesC. The radio-ligand (5 nM) was incubated with the sections for 3 h at room temperature. Washed and dried sections were exposed to tritium-sensitive film along with standards for 7-28 days and autoradiograms quantitated using NIH Image software. In the fetal human brain, low densities of THC-displaceable, region-specific binding could be observed as early as 14 weeks gestation. Receptor density increased slowly with gestational age but did not reach adult levels by the end of the second trimester (24 weeks gestation). In addition, the distribution pattern in the fetal brains was markedly different from the adult pattern. The most striking difference was the very low density of binding in the fetal caudate and putamen. In contrast, the globus pallidus pars medialis has almost-adult levels of cannabinoid receptors by 17-18 weeks gestation. The relatively low and regionally selective appearance of cannabinoid receptors in the fetal human brain may explain the relatively mild and selective nature of postnatal neurobehavioral deficits observed in infants exposed to cannabinoids in utero. (C) 2001 Academic Press.