PDF(Pubmed)
Abstract：
The impact of ethanol on the fetus is a significant concern as an estimated 2-5% of live births may be affected by prenatal alcohol exposure. This exposure can lead to various functional and structural abnormalities in the cerebral cortex, basal ganglia, diencephalon, and cerebellum, resulting in region-specific symptoms. The deficits relate to the motor and cognitive domains, affecting, in particular, general intelligence, attention, executive functions, language, memory, visual perception, and social skills-collectively called the fetal alcohol spectrum disorder (FASD). Recent studies suggest that damage to the developing cerebellum (in form of alcohol exposure) can impair the cortical targets of the cerebello-thalamo-cortical tract. This malfunction in the cerebello-cerebral loop optimization may be due to disruptions in the formation of the foundational elements of the internal model within the developing cerebellum. Alcohol exposure targets multiple nodes in the reciprocal loops between the cerebellum and cerebral cortex. Here, we examine the possibility that prenatal alcohol exposure damages the developing cerebellum and disrupts the connectivity within the cerebello-cerebral neuronal circuits, exacerbating FASD-related cortical dysfunctions. We propose that malfunctions between cerebellar internal model (critically involved in predictions) and cerebral regions contribute to the deficits observed in FASD. Given the major role of the cerebellum in motor, cognitive, and affective functions, we suggest that therapies should target these malfunctions to mitigate the burden of FASD. We discuss the concept of therapies oriented towards malfunctioning cerebello-cerebral loops (TOMCCLs), emphasizing anti-inflammatory strategies and treatments aimed at modulating cerebellar myelination to restore optimal and predictive cerebello-cerebral functions.
摘要：
乙醇对胎儿的影响是一个重要的问题，因为估计有2-5％的活产婴儿可能受到产前酒精暴露的影响。这种暴露会导致大脑皮层的各种功能和结构异常，基底神经节,间脑,还有小脑,导致特定区域的症状。这些缺陷与运动和认知领域有关，影响,特别是,一般智力，注意,执行功能，语言,记忆,视觉感知，和社交技能-统称为胎儿酒精谱系障碍（FASD）。最近的研究表明，对发育中的小脑的损害（以酒精暴露的形式）会损害小脑-丘脑-皮质道的皮质靶标。小脑循环优化中的这种故障可能是由于发育中的小脑内内部模型的基本元素的形成中断所致。酒精暴露针对小脑和大脑皮层之间的相互循环中的多个节点。这里,我们研究了产前酒精暴露损害发育中的小脑并破坏小脑神经元回路内的连通性的可能性，加剧FASD相关的皮质功能障碍。我们认为小脑内部模型（严重参与预测）和大脑区域之间的故障会导致FASD中观察到的缺陷。考虑到小脑在运动中的主要作用，认知，和情感功能，我们建议治疗应针对这些功能障碍,以减轻FASD的负担.我们讨论了针对小脑-脑环路（TOMCCLs）功能障碍的疗法的概念，强调抗炎策略和治疗旨在调节小脑髓鞘形成，以恢复最佳和预测性的小脑功能。
