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Entry of cannabidiol into the fetal, postnatal and adult rat brain
Cell and Tissue Research ( IF 3.6 ) Pub Date : 2024-02-17 , DOI: 10.1007/s00441-024-03867-w
Georgia Fitzpatrick , Yifan Huang , Fiona Qiu , Mark D. Habgood , Robert L. Medcalf , Heidi Ho , Katarzyna M. Dziegielewska , Norman R. Saunders

Cannabidiol is a major component of cannabis but without known psychoactive properties. A wide range of properties have been attributed to it, such as anti-inflammatory, analgesic, anti-cancer, anti-seizure and anxiolytic. However, being a fairly new compound in its purified form, little is known about cannabidiol brain entry, especially during development. Sprague Dawley rats at four developmental ages: embryonic day E19, postnatal day P4 and P12 and non-pregnant adult females were administered intraperitoneal cannabidiol at 10 mg/kg with [3H] labelled cannabidiol. To investigate the extent of placental transfer, the drug was injected intravenously into E19 pregnant dams. Levels of [3H]-cannabidiol in blood plasma, cerebrospinal fluid and brain were estimated by liquid scintillation counting. Plasma protein binding of cannabidiol was identified by polyacrylamide gel electrophoresis and its bound and unbound fractions measured by ultrafiltration. Using available RNA-sequencing datasets of E19 rat brain, choroid plexus and placenta, as well as P5 and adult brain and choroid plexus, expression of 13 main cannabidiol receptors was analysed. Results showed that cannabidiol rapidly entered both the developing and adult brains. Entry into CSF was more limited. Its transfer across the placenta was substantially restricted as only about 50% of maternal blood plasma cannabidiol concentration was detected in fetal plasma. Albumin was the main, but not exclusive, cannabidiol binding protein at all ages. Several transcripts for cannabidiol receptors were expressed in age- and tissue-specific manner indicating that cannabidiol may have different functional effects in the fetal compared to adult brain.



中文翻译:

大麻二酚进入胎儿、产后和成年大鼠大脑

大麻二酚是大麻的主要成分,但没有已知的精神活性特性。它具有多种特性,如抗炎、镇痛、抗癌、抗癫痫和抗焦虑。然而,作为一种纯化形式的相当新的化合物,人们对大麻二酚进入大脑的了解甚少,尤其是在发育过程中。对四个发育年龄的 Sprague Dawley 大鼠:胚胎 E19 天、出生后 P4 和 P12 天以及未怀孕的成年雌性大鼠腹膜内给予 10 mg/kg 的大麻二酚和 [ 3 H] 标记的大麻二酚。为了研究胎盘转移的程度,将药物静脉注射到 E19 怀孕母鼠体内。通过液体闪烁计数估计血浆、脑脊液和脑中的[ 3 H]-大麻二酚水平。通过聚丙烯酰胺凝胶电泳鉴定大麻二酚的血浆蛋白结合,并通过超滤测量其结合和未结合的部分。使用 E19 大鼠大脑、脉络丛和胎盘以及 P5 和成人大脑和脉络丛的现有 RNA 测序数据集,分析了 13 种主要大麻二酚受体的表达。结果表明,大麻二酚迅速进入发育中和成人的大脑。进入 CSF 的机会更加有限。它通过胎盘的转移受到很大限制,因为在胎儿血浆中仅检测到母体血浆大麻二酚浓度的约 50%。白蛋白是所有年龄段的主要但不是唯一的大麻二酚结合蛋白。大麻二酚受体的几种转录物以年龄和组织特异性方式表达,表明大麻二酚在胎儿大脑中可能具有与成人大脑不同的功能作用。

更新日期:2024-02-18
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