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Changes in the Number and Morphology of Dendritic Spines in the Hippocampus and Prefrontal Cortex of the C58/J Mouse Model of Autism
Frontiers in Cellular Neuroscience ( IF 5.3 ) Pub Date : 2021-09-20 , DOI: 10.3389/fncel.2021.726501
Isabel Barón-Mendoza 1 , Emely Maqueda-Martínez 1 , Mónica Martínez-Marcial 2 , Marisol De la Fuente-Granada 1 , Margarita Gómez-Chavarin 3 , Aliesha González-Arenas 1
Affiliation  

Autism spectrum disorder (ASD) has a broad range of neurobiological characteristics, including alterations in dendritic spines, where approximately 90% of excitatory synapses occur. Therefore, changes in their number or morphology would be related to atypical brain communication. The C58/J inbred mouse strain displays low sociability, impaired communication, and stereotyped behavior; hence, it is considered among the animal models suitable for the study of idiopathic autism. Thus, this study aimed to evaluate the dendritic spine differences in the hippocampus and the prefrontal cortex of C58/J mice. We found changes in the number of spines and morphology in a brain region-dependent manner: a subtle decrease in spine density in the prefrontal cortex, higher frequency of immature phenotype spines characterized by filopodia-like length or small morphology, and a lower number of mature phenotype spines with mushroom-like or wide heads in the hippocampus. Moreover, an in silico analysis showed single nucleotide polymorphisms (SNPs) at genes collectively involved in regulating structural plasticity with a likely association with ASD, including MAP1A (Microtubule-Associated Protein 1A), GRM7 (Metabotropic Glutamate Receptor, 7), ANKRD11 (Ankyrin Repeat Domain 11), and SLC6A4 (Solute Carrier Family 6, member 4), which might support the relationship between the C58/J strain genome, an autistic-like behavior, and the observed anomalies in the dendritic spines.



中文翻译:

C58/J 自闭症小鼠模型海马和前额叶皮层树突棘数量和形态的变化

自闭症谱系障碍 (ASD) 具有广泛的神经生物学特征,包括树突棘的改变,其中大约 90% 的兴奋性突触发生。因此,它们的数量或形态的变化将与非典型的大脑交流有关。C58/J 近交小鼠品系表现出低社交性、交流障碍和刻板行为;因此,它被认为是适合研究特发性自闭症的动物模型。因此,本研究旨在评估 C58/J 小鼠海马和前额叶皮层中树突棘的差异。我们发现脊椎数量和形态的变化与大脑区域相关:前额叶皮层的脊椎密度略有下降,以丝状伪足样长度或小形态为特征的未成熟表型刺的频率较高,海马中具有蘑菇状或宽头的成熟表型刺的数量较少。此外,一个电脑模拟 分析显示,共同参与调节结构可塑性的基因的单核苷酸多态性 (SNP) 可能与 ASD 相关,包括 MAP1A(微管相关蛋白 1A)、GRM7(代谢型谷氨酸受体,7)、ANKRD11(锚蛋白重复结构域 11)、和 SLC6A4(溶质载体家族 6,成员 4),这可能支持 C58/J 菌株基因组、自闭症样行为和观察到的树突棘异常之间的关系。

更新日期:2021-09-20
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