Development of Cannabinoid 1 Receptor Protein and Messenger RNA in Monkey Dorsolateral Prefrontal Cortex
Development of Cannabinoid 1 Receptor Protein and Messenger RNA in Monkey Dorsolateral Prefrontal Cortex
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DOI：
10.1093/cercor/bhp179
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发表时间：
2010-05-01
期刊：
影响因子：
3.7
通讯作者：
Lewis, David A.
中科院分区：
文献类型：
--
作者：
Eggan, Stephen M.;Mizoguchi, Yoshito;Lewis, David A.
青少年使用大麻与精神分裂症风险增加以及依赖于背外侧前额叶皮质（DLPFC）回路的认知过程受损有关。此外，母亲使用大麻与后代的认知功能障碍有关。大麻的作用是由大麻素1受体（CB1R）介导的，该受体在灵长类动物DLPFC中密度很高。为了确定CB1Rs的发育变化如何使DLPFC回路易受大麻暴露的影响，我们检测了81只猕猴（从胚胎82天到18岁）DLPFC中CB1R免疫反应（IR）轴突的密度和神经支配模式以及CB1R mRNA的表达。在围产期，灰质中CB1R的总体免疫反应性显著增加，并在出生后1周达到成人水平。然而，层流分析显示，CB1R-IR轴突密度在第1-2层随着年龄的增长而显著降低，但在第4层显著增加，尤其是在青春期。相比之下，CB1R mRNA水平在出生后1周最高，在接下来的2个月里下降，然后保持不变，直到成年。这些发现为大麻暴露对灵长类动物DLPFC回路成熟的离散、年龄依赖性影响提供了潜在的基础。
Adolescent cannabis use is associated with an increased risk of schizophrenia and with impairments in cognitive processes reliant on the circuitry of the dorsolateral prefrontal cortex (DLPFC). Additionally, maternal cannabis use is associated with cognitive dysfunction in offspring. The effects of cannabis are mediated by the cannabinoid 1 receptor (CB1R), which is present in high density in the primate DLPFC. In order to determine how developmental changes in CB1Rs might render DLPFC circuitry vulnerable to cannabis exposure, we examined the density and innervation patterns of CB1R-immunoreactive (IR) axons and the expression of CB1R mRNA in the DLPFC from 81 macaque monkeys, ranging in age from embryonic 82 days to 18 years. Overall CB1R immunoreactivity in the gray matter robustly increased during the perinatal period and achieved adult levels by 1 week postnatal. However, laminar analyses revealed that CB1R-IR axon density significantly decreased with age in layers 1-2 but significantly increased in layer 4, especially during adolescence. In contrast, CB1R mRNA levels were highest 1 week postnatal, declined over the next 2 months, and then remained unchanged into adulthood. These findings provide a potential substrate for discrete, age-dependent effects of cannabis exposure on the maturation of primate DLPFC circuitry.