Cheng Ning, Alshammari Fawaz, Hughes Elizabeth, Khanbabaei Maryam, Rho Jong M
Developmental Neurosciences Research Program, Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
O'Brien Centre for the Bachelor of Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
PLoS One. 2017 Jun 13;12(6):e0179409. doi: 10.1371/journal.pone.0179409. eCollection 2017.
Autism spectrum disorder (hereafter referred to as "ASD") is a heterogeneous neurodevelopmental condition characterized by impaired social communication and interactions, and restricted, repetitive activities or interests. Alterations in network connectivity and memory function are frequently observed in autism patients, often involving the hippocampus. However, specific changes during early brain development leading to disrupted functioning remain largely unclear. Here, we investigated the development of dendritic arbor of hippocampal CA1 pyramidal neurons in the BTBR T+tf/J (BTBR) mouse model of autism. BTBR mice display the defining behavioural features of autism, and also exhibit impaired learning and memory. We found that compared to control C57BL/6J (B6) animals, the lengths of both apical and basal dendrites were significantly greater in neonatal BTBR animals. Further, basal dendrites in the BTBR mice had higher branching complexity. In contrast, cross-sectional area of the soma was unchanged. In addition, we observed a similar density of CA1 pyramidal neurons and thickness of the neuronal layer between the two strains. Thus, there was a specific, compartmentalized overgrowth of dendrites during early development in the BTBR animals. Biochemical analysis further showed that the extracellular signal-regulated kinases (ERK) pathway was up-regulated in the hippocampus of neonatal BTBR animals. Since dendritic structure is critical for information integration and relay, our data suggest that altered development of dendrites could potentially contribute to impaired hippocampal function and behavior observed in the BTBR model, and that this might be related to increased activation of the ERK pathway.
自闭症谱系障碍（以下简称“ASD”）是一种异质性神经发育疾病，其特征为社交沟通和互动受损，以及存在受限的重复活动或兴趣。自闭症患者常出现网络连接和记忆功能改变，且往往涉及海马体。然而，导致功能紊乱的早期大脑发育过程中的具体变化仍不清楚。在此，我们研究了自闭症BTBR T+tf/J（BTBR）小鼠模型中海马体CA1锥体神经元树突棘的发育情况。BTBR小鼠表现出自闭症的典型行为特征，且学习和记忆也受损。我们发现，与对照C57BL/6J（B6）动物相比，新生BTBR动物的顶树突和基底树突长度均显著更长。此外，BTBR小鼠的基底树突具有更高的分支复杂性。相比之下，胞体的横截面积没有变化。此外，我们观察到这两个品系之间CA1锥体神经元的密度和神经层厚度相似。因此，在BTBR动物的早期发育过程中，树突存在特定的、分区性的过度生长。生化分析进一步表明，新生BTBR动物海马体中的细胞外信号调节激酶（ERK）通路上调。由于树突结构对信息整合和传递至关重要，我们的数据表明，树突发育改变可能导致BTBR模型中观察到的海马体功能和行为受损，这可能与ERK通路的激活增加有关。
