In utero exposure to cannabidiol disrupts select early-life behaviors in a sex-specific manner.
In utero exposure to cannabidiol disrupts select early-life behaviors in a sex-specific manner.
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DOI：
10.1038/s41398-022-02271-8
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发表时间：
2022-12-05
影响因子：
6.8
通讯作者：
Manzoni, Olivier J. J.
中科院分区：
文献类型：
--
作者：
Iezzi, Daniela;Caceres-Rodriguez, Alba;Chavis, Pascale;Manzoni, Olivier J. J.
大麻二酚（CBD）是大麻的主要成分之一，通常被认为是安全的。CBD穿过胎盘，其在妊娠期间的使用正在稳步增加，妊娠期CBD对产前生活和神经发育的影响尚不清楚。在这里，我们结合行为方法和深度学习分析来评估暴露于CBD的后代的性别依赖性新生儿行为。使妊娠C57 BL 6/J母鼠每天暴露于媒介物或CBD（3 mg/Kg，s.c.），从妊娠第5天到第18天。体重，幼鼠超声发声（USVs，PND 10）和归巢行为（PND 13）进行了定量的后代。因此，CBD处理母鼠的雄性（而非雌性）幼仔比假手术组体重增加更多。超声发声的粗特征存在性别差异。出生前CBD暴露的雄性幼犬发出较短的呼叫，而CBD女性发出更高频率的呼叫时，与他们的对照组相比。有显着的质的变化，在音节USV剧目反映在呼叫类型和通信模式。最后，归巢行为测试表明，CBD暴露的女性比男性更容易受到妊娠期CBD的影响。只有暴露于CBD的雌性幼鼠表现出运动和辨别能力下降。总之，这些结果表明，子宫内CBD暴露对早期发育年龄的新生儿的后果存在性别差异，这可能是成人精神病理学的预测。鉴于大麻和CBD在全球范围内的使用程度，这些发现挑战了CBD是一种普遍安全化合物的想法，并揭示了需要对围产期CBD暴露的影响进行更多研究。
Cannabidiol (CBD), one of the main components of cannabis, is generally considered safe. CBD crosses the placenta and its use during pregnancy is steadily increasing, the impact of gestational CBD’s effects on prenatal life and neurodevelopment are poorly understood. Here, we combined behavioral approaches and deep learning analysis to assess the sex-dependent neonatal behavior of CBD exposed progeny. Gestating C57BL6/J dams were exposed daily with vehicle or CBD (3 mg/Kg, s.c.), from gestational day 5 to 18. Body weight, pup ultrasound vocalizations (USVs, PND 10) and homing behavior (PND 13) were quantified in the progeny. Thus, male (but not female) pups from CBD-treated dams gained more weight than sham. There were sex-dependent differences in the coarse characteristics of ultrasonic vocalizations. Prenatally-CBD exposed male pups emitted shorter calls, whereas CBD females made more high frequency calls when compared with their control counterparts. There were significant qualitative changes in the syllabic USV repertoire reflected in call typologies and communication patterns. Finally, the homing behavior test showed that CBD-exposed females presented a greater vulnerability to gestational CBD than males. Only CBD-exposed female pups showed reduced motor and discriminatory abilities. Together the results suggest a sexual divergence in the consequences of in utero CBD exposure on neonates at early developmental ages, which may be predictive of adult psychopathology. Given the extent of cannabis and CBD use worldwide, these findings challenge the idea that CBD is a universally safe compound and reveal the need for additional studies on the effect of perinatal CBD exposure.
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影响因子：
2.1
作者：
Grant, Kimberly S.;Conover, Elizabeth;Chambers, Christina D.
通讯作者：
Chambers, Christina D.
影响因子：
4.7
作者：
Karimi-Haghighi, Saeideh;Razavi, Yasaman;Iezzi, Daniela;Scheyer, Andrew F.;Manzoni, Olivier;Haghparast, Abbas
通讯作者：
Haghparast, Abbas
影响因子：
8.2
作者：
Cirulli, F;Berry, A;Alleva, E
通讯作者：
Alleva, E
影响因子：
3.7
作者：
Antonelli, T;Tomasini, MC;Ferraro, L
通讯作者：
Ferraro, L
机器深度学习揭示 SPRED2 突变小鼠超声发声的基因型和年龄依赖性差异。
影响因子：
3.3
作者：
Hepbasli D;Gredy S;Ullrich M;Reigl A;Abeßer M;Raabe T;Schuh K
通讯作者：
Schuh K