{"title":"Maternal Immune Activation and Endocannabinoid System: Focus on Two-Hit Models of Schizophrenia.","authors":"Michele Santoni, Marco Pistis","doi":"10.1016/j.biopsych.2024.11.015","DOIUrl":null,"url":null,"abstract":"<p><p>The devastating effects of the COVID-19 pandemic have underscored the significant threat infectious diseases pose to our society. Pregnancy represents a particularly vulnerable period for 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), triggered by viral or bacterial infections, and the increased risk for neurodevelopmental disorders such as autism and schizophrenia. Genetic and environmental factors might contribute to the overall risk. Hence, 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 focuses on the interaction between MIA and cannabis use during adolescence, considering the role of the endocannabinoid system in neurodevelopment and in neurodevelopmental disorders. The endocannabinoid system, crucial for fetal brain development, may be disrupted by MIA, leading to adverse outcomes in adulthood. Recent research indicates the endocannabinoid system's significant role in the pathophysiology of neurodevelopmental disorders in preclinical models. However, findings on adolescent cannabinoid exposure in MIA-exposed animals reveal unexpected complexities, with several studies failing to support the exacerbation of MIA-related abnormalities. This review delves into the functional implications of the endocannabinoid system in MIA models, emphasizing 2-arachidonoylglycerol (2-AG) signaling's role in synaptic plasticity and neuroinflammation, and its relevance to the two-hit model of schizophrenia.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.biopsych.2024.11.015","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
The devastating effects of the COVID-19 pandemic have underscored the significant threat infectious diseases pose to our society. Pregnancy represents a particularly vulnerable period for 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), triggered by viral or bacterial infections, and the increased risk for neurodevelopmental disorders such as autism and schizophrenia. Genetic and environmental factors might contribute to the overall risk. Hence, 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 focuses on the interaction between MIA and cannabis use during adolescence, considering the role of the endocannabinoid system in neurodevelopment and in neurodevelopmental disorders. The endocannabinoid system, crucial for fetal brain development, may be disrupted by MIA, leading to adverse outcomes in adulthood. Recent research indicates the endocannabinoid system's significant role in the pathophysiology of neurodevelopmental disorders in preclinical models. However, findings on adolescent cannabinoid exposure in MIA-exposed animals reveal unexpected complexities, with several studies failing to support the exacerbation of MIA-related abnormalities. This review delves into the functional implications of the endocannabinoid system in MIA models, emphasizing 2-arachidonoylglycerol (2-AG) signaling's role in synaptic plasticity and neuroinflammation, and its relevance to the two-hit model of schizophrenia.
期刊介绍:
Biological Psychiatry is an official journal of the Society of Biological Psychiatry and was established in 1969. It is the first journal in the Biological Psychiatry family, which also includes Biological Psychiatry: Cognitive Neuroscience and Neuroimaging and Biological Psychiatry: Global Open Science. The Society's main goal is to promote excellence in scientific research and education in the fields related to the nature, causes, mechanisms, and treatments of disorders pertaining to thought, emotion, and behavior. To fulfill this mission, Biological Psychiatry publishes peer-reviewed, rapid-publication articles that present new findings from original basic, translational, and clinical mechanistic research, ultimately advancing our understanding of psychiatric disorders and their treatment. The journal also encourages the submission of reviews and commentaries on current research and topics of interest.