Laboratory of Disease Modeling, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Institut Pasteur de São Paulo, São Paulo, Brazil.
Adv Neurobiol. 2024;39:269-284. doi: 10.1007/978-3-031-64839-7_11.
Autism spectrum disorder (ASD) comprises a complex neurodevelopmental condition characterized by an impairment in social interaction, involving communication deficits and specific patterns of behaviors, like repetitive behaviors. ASD is clinically diagnosed and usually takes time, typically occurring not before four years of age. Genetic mutations affecting synaptic transmission, such as neuroligin and neurexin, are associated with ASD and contribute to behavioral and cognitive deficits. Recent research highlights the role of astrocytes, the brain's most abundant glial cells, in ASD pathology. Aberrant Ca signaling in astrocytes is linked to behavioral deficits and neuroinflammation. Notably, the cytokine IL-6 overexpression by astrocytes impacts synaptogenesis. Altered neurotransmitter levels, disruptions in the blood-brain barrier, and cytokine dysregulation further contribute to ASD complexity. Understanding these astrocyte-related mechanisms holds promise for identifying ASD subtypes and developing targeted therapies.
自闭症谱系障碍(ASD)是一种复杂的神经发育障碍,其特征是社交互动受损,包括沟通障碍和特定的行为模式,如重复行为。ASD 通过临床诊断,通常需要时间,通常在四岁之前不会出现。影响突触传递的基因突变,如神经原粘连蛋白和神经连接蛋白,与 ASD 有关,并导致行为和认知缺陷。最近的研究强调了星形胶质细胞在 ASD 病理中的作用,星形胶质细胞是大脑中最丰富的神经胶质细胞。星形胶质细胞中异常的 Ca 信号与行为缺陷和神经炎症有关。值得注意的是,星形胶质细胞中细胞因子 IL-6 的过度表达会影响突触发生。神经递质水平的改变、血脑屏障的破坏以及细胞因子失调进一步导致 ASD 的复杂性。了解这些与星形胶质细胞相关的机制有望确定 ASD 的亚型并开发靶向治疗方法。