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大麻二酚可减轻早期酒精暴露诱导的小鼠认知功能障碍和神经炎症。

Cannabidiol attenuates cognitive deficits and neuroinflammation induced by early alcohol exposure in a mice model.

机构信息

Neurobiology of Behaviour Research Group (GReNeC-NeuroBio), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.

Neonatology Unit, ICGON, IDIBAPS, Hospital Clínic-Maternitat, BCNatal, Barcelona, Spain.

出版信息

Biomed Pharmacother. 2021 Sep;141:111813. doi: 10.1016/j.biopha.2021.111813. Epub 2021 Jun 11.

Abstract

Foetal alcohol spectrum disorder (FASD) is the umbrella term used to describe the physical and mental disabilities induced by alcohol exposure during development. Early alcohol exposure induces cognitive impairments resulting from damage to the central nervous system (CNS). The neuroinflammatory response accompanied by neurodegenerative mechanisms contribute to those detrimental alterations. Cannabidiol (CBD) has recently emerged as an anti-inflammatory drug that might be useful to treat several neuropsychiatric disorders. In our study, we assessed the effects of CBD on long-lasting cognitive deficits induced by early alcohol exposure. Furthermore, we analysed long-term pro-inflammatory and apoptotic markers within the prefrontal cortex and hippocampus. To model alcohol binge drinking during gestational and lactation periods, we used pregnant C57BL/6 female mice with time-limited access to 20% v/v alcohol solution. Following the prenatal and lactation alcohol exposure (PLAE), we treated the male and female offspring with CBD from post-natal day (PD) 25 until PD34, and we evaluated their cognitive performance at PD60. Our results showed that CBD treatment during peri-adolescence period ameliorates cognitive deficits observed in our FASD-like mouse model, without sex differences. Moreover, CBD restores the PLAE-induced increased levels of TNFα and IL-6 in the hippocampus. Thus, our study provides new insights for CBD as a therapeutic agent to counteract cognitive impairments and neuroinflammation caused by early alcohol exposure.

摘要

胎儿酒精谱系障碍(FASD)是一个用来描述在发育过程中暴露于酒精引起的身体和精神残疾的术语。早期酒精暴露会导致中枢神经系统(CNS)损伤引起的认知障碍。神经炎症反应和神经退行性机制共同导致了这些有害的改变。大麻二酚(CBD)最近作为一种抗炎药物出现,可能对治疗多种神经精神疾病有用。在我们的研究中,我们评估了 CBD 对早期酒精暴露引起的长期认知缺陷的影响。此外,我们还分析了前额叶皮层和海马体中长期的促炎和凋亡标志物。为了模拟妊娠期和哺乳期的酒精 binge 饮酒,我们使用有限时间接触 20% v/v 酒精溶液的怀孕 C57BL/6 雌性小鼠。在产前和哺乳期酒精暴露(PLAE)后,我们从出生后第 25 天(PD)到第 34 天用 CBD 治疗雄性和雌性后代,并在 PD60 评估它们的认知表现。我们的结果表明,在青春期前期间用 CBD 治疗可以改善我们的 FASD 样小鼠模型中观察到的认知缺陷,且无性别差异。此外,CBD 恢复了 PLAE 诱导的海马体中 TNFα 和 IL-6 水平的升高。因此,我们的研究为 CBD 作为一种治疗剂提供了新的见解,以对抗早期酒精暴露引起的认知障碍和神经炎症。

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