第四军医大学武胜昔等研究人员合作在Shank3B KO小鼠的出生后不同发育阶段中，揭示Shank3在树突形态和突触功能中的作用。这一研究成果于2024年12月18日在线发表在国际学术期刊《神经科学通报》上。

据了解，ASD的特点是早期出现的神经发育异常，但遗传因素对这些过程的时间性动态仍然没有充分了解。

研究人员旨在阐明与自闭症单基因致病原因相关的Shank3基因在早期发育过程中的作用，为自闭症谱系障碍（ASD）潜在干预的时机和机制提供信息。利用Shank3B敲除（KO）小鼠模型，研究人员通过Golgi染色观察了树突形态。

结合电生理记录测量前扣带皮层（ACC）的突触功能，研究人员揭示了Shank3的表达及其对神经元成熟的影响，其涵盖不同的出生后发育阶段。

纵向分析发现，尽管Shank3B敲除小鼠在出生后一周表现出正常的神经元形态，但在出生后两到三周时，树突生长和突触活动出现了显著损伤。这些发现突出了Shank3对ACC神经元和突触成熟至关重要的发育窗口期。

附：英文原文

Title: Deciphering the Role of Shank3 in Dendritic Morphology and Synaptic Function Across Postnatal Developmental Stages in the Shank3B KO Mouse

Author: Yang, Jing, Ma, Guaiguai, Du, Xiaohui, Xie, Jinyi, Wang, Mengmeng, Wang, Wenting, Guo, Baolin, Wu, Shengxi

Issue&Volume: 2024-12-18

Abstract: Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.

DOI: 10.1007/s12264-024-01330-y

Source: https://link.springer.com/article/10.1007/s12264-024-01330-y