Xu Xiaoou, Tan Li, Zhang Xiaojuan
Department for Science and Technology Management and Education, Chongqing Population and Family Planning Science and Technology Research Institute, 401120 Chongqing, China.
Department of Clinical Medicine, Chongqing Medical and Pharmaceutical College, 401331 Chongqing, China.
Alpha Psychiatry. 2025 Apr 1;26(2):39444. doi: 10.31083/AP39444. eCollection 2025 Apr.
To investigate the potential toxic effects of prenatal exposure to valproic acid (VPA) on microglia-neuron communication in the brain, with a specific focus on the alterations in key molecules involved in this process, namely CX3CL1/CX3CR1 and CD200/CD200R, during the early stages of life in a rat model of autism.
Pregnant female rats were administered either sterile saline or VPA on embryonic day 12.5. The brains of the rat offspring were collected on postnatal day 30 for analysis. Immunohistochemical techniques and enzyme-linked immunosorbent assay (ELISA) were employed to assess changes in microglia-neuron crosstalk.
The study revealed a significant reduction in CD200 levels within the hippocampus of rats on postnatal day 30 following prenatal exposure to VPA, indicating an impairment in CD200/CD200R signaling. Additionally, there was no observed increase in microglial numbers or any pathological alterations in the hippocampus. Additionally, no significant changes in the levels of CX3CL1 and CX3CR1 were noted in the VPA-exposed rats compared with the control group.
Prenatal exposure to VPA resulted in a decrease in CD200 expression within the hippocampus, potentially disrupting the communication between microglia and neurons. The findings suggest that VPA may modify the interactions between microglia and neurons, which could lead to neuroinflammation due to hyperactivated microglia. These disruptions have the potential to affect synaptic connectivity and contribute to the development of neurodevelopmental disorders, including autism. Further research is necessary to clarify the underlying mechanisms and implications for pathological conditions associated with autism spectrum disorder (ASD).
研究产前暴露于丙戊酸（VPA）对大脑中微胶质细胞与神经元通讯的潜在毒性作用，特别关注自闭症大鼠模型生命早期阶段参与此过程的关键分子即CX3CL1/CX3CR1和CD200/CD200R的变化。
在胚胎第12.5天给怀孕的雌性大鼠注射无菌生理盐水或VPA。在出生后第30天收集大鼠后代的大脑进行分析。采用免疫组织化学技术和酶联免疫吸附测定（ELISA）来评估微胶质细胞与神经元相互作用的变化。
研究显示，产前暴露于VPA的大鼠在出生后第30天海马体内CD200水平显著降低，表明CD200/CD200R信号传导受损。此外，未观察到海马体中微胶质细胞数量增加或任何病理改变。另外，与对照组相比，暴露于VPA的大鼠中CX3CL1和CX3CR1水平未发现显著变化。
产前暴露于VPA导致海马体内CD200表达降低，可能破坏微胶质细胞与神经元之间的通讯。研究结果表明，VPA可能改变微胶质细胞与神经元之间的相互作用，这可能由于微胶质细胞过度激活而导致神经炎症。这些破坏有可能影响突触连接，并促成包括自闭症在内的神经发育障碍的发生。有必要进一步研究以阐明与自闭症谱系障碍（ASD）相关的病理状况的潜在机制及其影响。
