Abstract：
Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.
摘要：
自闭症谱系障碍（ASD）是一组神经发育疾病，包括刻板和重复的行为，除了社会和感觉运动缺陷。解剖学和功能证据表明纹状体非典型成熟。星形胶质细胞调节突触回路的成熟和可塑性，钙信号受损与重复行为和非典型社会交往有关。通过产前暴露于丙戊酸（VPA），在ASD的临床前模型中研究了大鼠纹状体星形胶质细胞中记录的自发性钙瞬变（SCT）。我们的结果显示感觉运动延迟，增强的胶质原纤维酸性蛋白-星形胶质细胞表达的典型中间丝蛋白-和GABAA-ρ3通过发育的表达减少，和SCT的频率增加，潜伏期减少，导致VPA模型中的振幅减小。抽搐的微毒素，一种GABAA（γ-氨基丁酸A型）受体拮抗剂，降低了两个实验组的SCT频率，但在临床前ASD模型中将该参数恢复到对照水平。在两个实验组中，微毒素均降低了SCT的幅度和潜伏期。Nipcoticacid,GABA摄取抑制剂，仅降低对照组的平均振幅。然而，nipcotic酸增加了频率，但减少了两个实验组的潜伏期。因此，我们得出结论，纹状体星形胶质细胞表现出由GABAA介导的信号调节的SCT，产前暴露于VPA会干扰这种调谐。
