Department of Physiology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey.
Neurobiology Research Unit, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Int J Dev Neurosci. 2024 Aug;84(5):392-405. doi: 10.1002/jdn.10335. Epub 2024 May 9.
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.
氯化胆碱作为一种必需的营养物质，是乙酰胆碱和细胞膜磷脂合成的前体，具有神经保护作用，与神经和神经退行性疾病有关。其对自闭症谱系障碍（一种神经发育障碍）的贡献尚不清楚。因此，我们旨在评估氯化胆碱对自闭症模型大鼠社会行为以及组织病理学和生化变化的影响。自闭症模型通过在妊娠第 10 天给予 100μg/kg 脂多糖（LPS）诱导。氯化胆碱治疗（100mg/kg/天）于 PN5 开始，并持续至 PN50。通过三腔社交、旷场和被动回避学习测试评估社交缺陷。测量肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）和白细胞介素-17（IL-17）、神经生长因子（NGF）和谷氨酸脱羧酶 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数量以及神经胶质纤维酸性蛋白（GFAP）表达。在雄性大鼠中，与盐水处理组相比，氯化胆碱处理的雄性大鼠在社会新颖性和被动回避学习测试中表现出显著差异。在雄性和雌性中，氯化胆碱处理后 TNF-α、IL-2 和 IL-17 均显著降低。NGF 和 GAD67 水平在雌性中没有变化，而在雄性中则有显著差异。组织学上，在氯化胆碱处理组的海马 CA1 和 CA3 区和小脑观察到明显的神经胶质增生变化。在 LPS 诱导的自闭症雄性大鼠模型中，氯化胆碱治疗通过神经炎症、神经营养和神经递质途径对社会行为和神经炎症具有改善作用。
