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产前Δ-9-四氢大麻酚暴露对小鼠脑发育的影响:一项从胎儿期到成年期的磁共振成像研究。

Impact of prenatal delta-9-tetrahydrocannabinol exposure on mouse brain development: a fetal-to-adulthood magnetic resonance imaging study.

作者信息

Cupo Lani, Vecchiarelli Haley A, Gallino Daniel, VanderZwaag Jared, Bradshaw Katerina, Phan Annie, Khakpour Mohammadparsa, Ben-Azu Benneth, Guma Elisa, Fouquet Jérémie P, Spring Shoshana, Nieman Brian J, Devenyi Gabriel A, Tremblay Marie-Eve, Chakravarty M Mallar

机构信息

McGill University, Department of Psychiatry, Montréal, QC, Canada.

Computational Brain Anatomy (CoBrA) Laboratory, Cerebral Imaging Centre, Douglas Research Centre, Verdun, QC, Canada.

出版信息

Mol Psychiatry. 2025 Sep 17. doi: 10.1038/s41380-025-03189-5.

Abstract

While cannabis use during pregnancy is often perceived as harmless, little is known about its consequences on offspring neurodevelopment. There is an urgent need to map the effects of prenatal cannabis exposure on the brain through the course of the lifespan. We used magnetic resonance imaging spanning nine timepoints, behavioral assays, and electron microscopy to build a trajectory from gestation to adulthood in mice exposed prenatally to delta-9-tetrahydrocannabinol (THC). Our results demonstrate a spatio-temporal patterning, with ventriculomegaly in THC-exposed embryos followed by a deceleration of brain growth in neonates that is sustained until adulthood, especially in females. We observed consistently impacted regions in both the cortex and subcortex, aligned with sex-dependent changes to social behavior in neonates and increased anxiety-like behavior in adolescents. Our results suggest prenatal THC exposure has a sustained sex-dependent impact on neurodevelopment that may persist into early adulthood.

摘要

虽然孕期使用大麻通常被认为是无害的,但对于其对后代神经发育的影响却知之甚少。迫切需要通过整个生命周期来描绘产前接触大麻对大脑的影响。我们使用了跨越九个时间点的磁共振成像、行为分析和电子显微镜,来构建产前暴露于δ-9-四氢大麻酚(THC)的小鼠从妊娠期到成年期的发育轨迹。我们的结果显示出一种时空模式,即暴露于THC的胚胎出现脑室扩大,随后新生儿脑生长减速,并持续到成年期,尤其是雌性小鼠。我们观察到皮层和皮层下区域均受到持续影响,这与新生儿社交行为的性别依赖性变化以及青少年焦虑样行为增加相一致。我们的结果表明,产前暴露于THC对神经发育有持续的性别依赖性影响,这种影响可能会持续到成年早期。

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