产前THC暴露会诱导长期的,取决于性别的认知功能障碍,与前额叶皮质-海马体网络中的脂质和神经病理相关
Mohammed H Sarikahya1,2, Samantha L Cousineau3, Marta De Felice1,2
1Addiction Research Group, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Molecular psychiatry
|July 31, 2023
概括
产前大麻暴露 (PCE) 会导致后代的长期认知缺陷,有明显的性别特异性脑部变化. 这些影响包括神经活动,蛋白质表达和前额叶皮质和海马体中多不和脂肪酸缺乏的改变.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 孕产妇使用大麻的数量正在增加,需要对产前暴露效应进行研究.
- Δ9-四大麻 (THC) 对内分泌系统 (ECS) 产生影响,该系统对由前额叶皮层 (PFC) 和海马体调节的认知功能至关重要.
- 多不和脂肪酸 (PUFA) 对ECS功能和大脑发育至关重要.
研究的目的:
- 研究产前大麻暴露 (PCE) 对后代的长期认知和神经生物学后果.
- 确定这些影响背后的性别特异性机制.
- 探索PUFA缺陷在PCE诱导的神经生物学变化中的作用.
主要方法:
- 利用动物模型进行产前大麻暴露 (PCE).
- 进行了电生理学记录,以评估PFC和海马中的神经活动.
- 进行蛋白质表达分析和MALDI IMS,检查分子变化和PUFA水平.
主要成果:
- 后代表现出长期的认知缺陷与性别不同的神经变化.
- PFC金字塔神经元在两性都过度活跃;腹部海马体 (vHIPP) 活动在男性中低活跃,在女性中过度活跃.
- 在PFC和海马体中观察到蛋白质表达的性别特异性变化以及多可萨赫萨酸 (DHA) 和酸 (ARA) 的缺乏.
结论:
- PCE导致持久的PFC-海马体电路功能障碍,具有明显的性别特异的神经生物学途径.
- 神经PUFA信号的异常可能导致观察到的认知和行为缺陷.
- 这些发现强调了了解与产前大麻暴露相关的性别依赖风险的必要性.
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