Chen Bin, Xu Xinxin, Wang Yue, Yang Zhuo, Liu Chunhua, Zhang Tao
College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071 People's Republic of China.
School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071 People's Republic of China.
Cogn Neurodyn. 2024 Aug;18(4):1563-1574. doi: 10.1007/s11571-023-09996-2. Epub 2023 Aug 19.
Autism spectrum disorder (ASD) is a general neurodevelopmental disease characterized by unusual social communication and rigid, repetitive behavior patterns. The purpose of this study was to investigate the effects of ASD on the alteration of neural oscillatory patterns and synaptic plasticity, which commonly supported a wide range of basic and higher memory activities. Accordingly, a prenatal valproic acid (VPA) exposure rat model was established for studying autism. The behavioral experiments showed that the social orientation declined and the memory ability was significantly impaired in VPA rats, which was closely associated with the synaptic plasticity deficits. Neural oscillation is the rhythmic neuron-activity, and the pathological characteristics and neurological changes in autism may be peeped at the neural oscillatory analysis. Interestingly, neural oscillatory analysis showed that prenatal VPA exposure reduced the low-frequency power but increased high-frequency gamma (HG) power in the hippocampus CA1 area. Meanwhile, the coherence and synchronization between CA3 and CA1 were abnormally increased in the VPA group, especially in theta and HG rhythms. Furthermore, the cross-frequency coupling strength of theta-LG in the CA1 and CA3 → CA1 pathway was significantly attenuated, but the theta-HG coupling strength was increased. Additionally, prenatal VPA exposure inhibited the expression of SYP and NR2B but enhanced the expression of PSD-95 along with decreased synaptic plasticity. The neural oscillatory patterns in VPA-induced offspring were disturbed with the intensity and direction of neural information flow disordered, which are consistent with the changes in synaptic plasticity, suggesting that the decline in synaptic plasticity is the underlying mechanism.
自闭症谱系障碍（ASD）是一种常见的神经发育疾病，其特征为异常的社交沟通以及刻板、重复的行为模式。本研究的目的是调查ASD对神经振荡模式改变和突触可塑性的影响，这些通常支持广泛的基础和高级记忆活动。因此，建立了产前丙戊酸（VPA）暴露大鼠模型来研究自闭症。行为实验表明，VPA大鼠的社交定向能力下降，记忆能力显著受损，这与突触可塑性缺陷密切相关。神经振荡是有节律的神经元活动，通过神经振荡分析可以窥探自闭症的病理特征和神经学变化。有趣的是，神经振荡分析表明，产前VPA暴露降低了海马CA1区的低频功率，但增加了高频γ（HG）功率。同时，VPA组中CA3和CA1之间的相干性和同步性异常增加，尤其是在θ和HG节律中。此外，CA1和CA3→CA1通路中θ-LG的交叉频率耦合强度显著减弱，但θ-HG耦合强度增加。另外，产前VPA暴露抑制了SYP和NR2B的表达，但增强了PSD-95的表达，同时突触可塑性降低。VPA诱导的后代的神经振荡模式受到干扰，神经信息流的强度和方向紊乱，这与突触可塑性的变化一致，表明突触可塑性下降是其潜在机制。
