Santoni Michele, Pistis Marco
Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy; Unit of Clinical Pharmacology, University Hospital, Cagliari, Italy.
Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy; Unit of Clinical Pharmacology, University Hospital, Cagliari, Italy; Neuroscience Institute, National Research Council of Italy, Cagliari, Italy.
Biol Psychiatry. 2024 Nov 29. doi: 10.1016/j.biopsych.2024.11.015.
The devastating effects of the COVID-19 pandemic have underscored the significant threat that infectious diseases pose to our society. Pregnancy represents a period of heightened vulnerability to infections, which can compromise maternal health and increase the risk of neurodevelopmental disorders in offspring. Preclinical and clinical investigations suggest a potential association between maternal immune activation (MIA), which is triggered by viral or bacterial infections, and increased risk for neurodevelopmental disorders such as autism and schizophrenia. Genetic and environmental factors may contribute to the overall risk. Therefore, the two-hit hypothesis of schizophrenia suggests that MIA could act as a first trigger, with subsequent factors, such as stress or drug abuse, exacerbating latent abnormalities. A growing body of research is focused on the interaction between MIA and cannabis use during adolescence, considering the role of the endocannabinoid (eCB) system in neurodevelopment and in neurodevelopmental disorders. The eCB system, crucial for fetal brain development, may be disrupted by MIA, leading to adverse outcomes in adulthood. Recent research indicates the eCB system's significant role in the pathophysiology of neurodevelopmental disorders in preclinical models. However, findings on adolescent cannabinoid exposure in MIA-exposed animals have revealed unexpected complexities, with several studies failing to support the exacerbation of MIA-related abnormalities. In this review, we delve into the functional implications of the eCB system in MIA models, emphasizing the role of 2-AG (2-arachidonoylglycerol) signaling in synaptic plasticity and neuroinflammation and its relevance to the two-hit model of schizophrenia.
新冠疫情的毁灭性影响凸显了传染病对我们社会构成的重大威胁。孕期是感染易感性增强的时期，感染会损害孕产妇健康，并增加后代患神经发育障碍的风险。临床前和临床研究表明，由病毒或细菌感染引发的母体免疫激活（MIA）与自闭症和精神分裂症等神经发育障碍风险增加之间可能存在关联。遗传和环境因素可能导致总体风险增加。因此，精神分裂症的双重打击假说表明，MIA可能是第一个触发因素，随后诸如压力或药物滥用等因素会加剧潜在异常。考虑到内源性大麻素（eCB）系统在神经发育和神经发育障碍中的作用，越来越多的研究聚焦于青春期MIA与大麻使用之间的相互作用。对胎儿大脑发育至关重要的eCB系统可能会因MIA而受到干扰，从而导致成年期出现不良后果。最近的研究表明，eCB系统在临床前模型的神经发育障碍病理生理学中具有重要作用。然而，对暴露于MIA的动物进行青少年大麻素暴露的研究结果揭示了意想不到的复杂性，几项研究未能支持MIA相关异常的加剧。在本综述中，我们深入探讨了eCB系统在MIA模型中的功能意义，强调2-AG（2-花生四烯酸甘油酯）信号在突触可塑性和神经炎症中的作用及其与精神分裂症双重打击模型的相关性。
