Abstract：
The neuroprotective effects of choline chloride, an essential nutrient, a precursor for the acetylcholine and synthesis of membrane phospholipids, have been associated with neurological and neurodegenerative diseases. Its contribution to autism spectrum disorder, a neurodevelopmental disorder, remains unknown. Thus, we aimed to evaluate the effects of choline chloride on social behaviours, and histopathological and biochemical changes in a rat autism model. The autism model was induced by administration of 100 μg/kg lipopolysaccharide (LPS) on the 10th day of gestation. Choline chloride treatment (100 mg/kg/day) was commenced on PN5 and maintained until PN50. Social deficits were assessed by three-chamber sociability, open field, and passive avoidance learning tests. Tumour necrosis factor alpha (TNF-α), interleukin-2 (IL) and IL-17, nerve growth factor (NGF), and glutamate decarboxylase 67 (GAD67) levels were measured to assess neuroinflammatory responses. In addition, the number of hippocampal and cerebellar neurons and glial fibrillary acidic protein (GFAP) expression were evaluated. Social novelty and passive avoidance learning tests revealed significant differences in choline chloride-treated male rats compared with saline-treated groups. TNF-α, IL-2, and IL-17 were significantly decreased after choline chloride treatment in both males and females. NGF and GAD67 levels were unchanged in females, while there were significant differences in males. Histologically, significant changes in terms of gliosis were detected in hippocampal CA1 and CA3 regions and cerebellum in choline chloride-treated groups. The presence of ameliorative effects of choline chloride treatment on social behaviour and neuroinflammation through neuroinflammatory, neurotrophic, and neurotransmission pathways in a sex-dependent rat model of LPS-induced autism was demonstrated.
摘要：
氯化胆碱的神经保护作用，一种必需的营养素，乙酰胆碱和膜磷脂合成的前体，与神经和神经退行性疾病相关。它对自闭症谱系障碍的贡献，神经发育障碍,仍然未知。因此，我们的目的是评估氯化胆碱对社会行为的影响，以及大鼠自闭症模型的组织病理学和生化变化。通过在妊娠第10天施用100μg/kg脂多糖（LPS）来诱导自闭症模型。在PN5上开始氯化胆碱处理(100mg/kg/天)并维持直至PN50。社会赤字是通过三室社交能力来评估的，开放领域，和被动回避学习测试。肿瘤坏死因子α(TNF-α),白细胞介素-2（IL）和IL-17，神经生长因子（NGF），测量谷氨酸脱羧酶67（GAD67）水平以评估神经炎症反应。此外,评估海马和小脑神经元的数量和胶质纤维酸性蛋白（GFAP）的表达。社会新颖性和被动回避学习测试显示，与生理盐水治疗组相比，氯化胆碱治疗的雄性大鼠存在显着差异。TNF-α,IL-2和IL-17在男性和女性的氯化胆碱治疗后显著降低。女性的NGF和GAD67水平没有变化，而男性有显著差异。组织学上,在氯化胆碱治疗组中,在海马CA1和CA3区以及小脑中检测到神经胶质增生方面的显著变化.氯化胆碱治疗通过神经炎对社会行为和神经炎症的改善作用，神经营养，并证明了LPS诱导的自闭症的性别依赖性大鼠模型中的神经传递途径。
