Influence of Prenatal Drug Exposure, Maternal Inflammation, and Parental Aging on the Development of Autism Spectrum Disorder.
Influence of Prenatal Drug Exposure, Maternal Inflammation, and Parental Aging on the Development of Autism Spectrum Disorder.
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产前药物暴露、母亲炎症和父母年龄对自闭症谱系障碍发生的影响
DOI：
10.3389/fpsyt.2022.821455
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发表时间：
2022
影响因子：
4.7
通讯作者：
Ikeda K
中科院分区：
文献类型：
--
作者：
Sato A;Kotajima-Murakami H;Tanaka M;Katoh Y;Ikeda K
自闭症谱系障碍（ASD）影响相互的社会交往，并产生异常的重复性，限制性的行为和兴趣。ASD的不同原因分为遗传改变和环境风险。ASD的患病率几十年来一直在上升，这可能与环境风险有关，因为很难认为与ASD相关的遗传疾病的患病率会突然增加。后者包括（1）暴露于药物，如丙戊酸（VPA）和选择性5-羟色胺再摄取抑制剂（SSRIs）（2），妊娠期间的母体并发症，包括感染和妊娠期高血压疾病，以及（3）父母年龄高。流行病学研究表明，产前暴露于VPA和母体炎症在ASD的发展中具有致病作用。VPA被认为通过几种不同的机制对胎脑产生有害影响，如γ-氨基丁酸信号传导的改变、组蛋白脱乙酰酶的抑制、叶酸代谢的破坏和雷帕霉素的哺乳动物靶点的激活。由不同刺激引起的母体炎症在胎儿脑中聚集在较高的促炎细胞因子负荷上。母亲暴露于SSRIs的啮齿动物模型在后代中产生ASD样行为，但与这些临床前发现的临床相关性尚不确定。妊娠期高血压疾病和父母高龄会增加人类ASD的风险，但在动物模型中对其机制的研究很少。环境因素与ASD相关的机制的证据进行了讨论，这可能有助于ASD的预防和治疗干预措施的发展。
Autism spectrum disorder (ASD) affects reciprocal social interaction and produces abnormal repetitive, restrictive behaviors and interests. The diverse causes of ASD are divided into genetic alterations and environmental risks. The prevalence of ASD has been rising for several decades, which might be related to environmental risks as it is difficult to consider that the prevalence of genetic disorders related to ASD would increase suddenly. The latter includes (1) exposure to medications, such as valproic acid (VPA) and selective serotonin reuptake inhibitors (SSRIs) (2), maternal complications during pregnancy, including infection and hypertensive disorders of pregnancy, and (3) high parental age. Epidemiological studies have indicated a pathogenetic role of prenatal exposure to VPA and maternal inflammation in the development of ASD. VPA is considered to exert its deleterious effects on the fetal brain through several distinct mechanisms, such as alterations of γ-aminobutyric acid signaling, the inhibition of histone deacetylase, the disruption of folic acid metabolism, and the activation of mammalian target of rapamycin. Maternal inflammation that is caused by different stimuli converges on a higher load of proinflammatory cytokines in the fetal brain. Rodent models of maternal exposure to SSRIs generate ASD-like behavior in offspring, but clinical correlations with these preclinical findings are inconclusive. Hypertensive disorders of pregnancy and advanced parental age increase the risk of ASD in humans, but the mechanisms have been poorly investigated in animal models. Evidence of the mechanisms by which environmental factors are related to ASD is discussed, which may contribute to the development of preventive and therapeutic interventions for ASD.
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影响因子：
3.3
作者：
Akintunde, Marjannie Eloi;Rose, Melissa;de Water, Judy Van
通讯作者：
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影响因子：
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64.8
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作者：
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通讯作者：
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