Department for Life Qualities Studies, University of Bologna, Rimini, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Clin Neurol Neurosurg. 2020 Jul;194:105870. doi: 10.1016/j.clineuro.2020.105870. Epub 2020 May 20.
Down syndrome (DS) is a genetic condition characterized by cognitive disability starting from infancy. Children with DS exhibit deficits in several cognitive domains, including executive function, i.e., a set of cognitive processes that heavily depend on higher-order thalamic nuclei. The goal of this study was to establish whether executive function-related thalamic nuclei of fetuses with DS exhibit neuroanatomical alterations that may contribute to the defects in higher-order control processes seen in children with DS.
In brain sections from fetuses with DS and control fetuses (gestational week 17-22), we evaluated the cellularity in the mediodorsal nucleus (MD), the centromedian nucleus (CM), and the parafascicular nucleus (PF) of the thalamus and the density of proliferating cells in the third ventricle.
We found that all three nuclei had a notably reduced cell density. This defect was associated with a reduced density of proliferating cells in the third ventricle, suggesting that the reduced cellularity in the MD, CM, and PF of fetuses with DS was due to neurogenesis impairment. The separate evaluation of projection neurons and interneurons in the MD, CM, and PF showed that in fetuses with DS the density of projection neurons was reduced, with no changes in interneuron density.
This study provides novel evidence for DS-linked cellularity alterations in the MD, CM, and PF and suggests that altered signal processing in these nuclei may be involved in the impairment in higher-order control processes observed in individuals with DS starting from infancy.
唐氏综合征（DS）是一种遗传性疾病，其认知障碍始于婴儿期。DS 患儿在多个认知领域存在缺陷，包括执行功能，即一组严重依赖高级丘脑核的认知过程。本研究的目的是确定 DS 胎儿的执行功能相关丘脑核是否存在神经解剖学改变，这些改变可能导致 DS 患儿出现高级控制过程缺陷。
在来自 DS 胎儿和对照胎儿（妊娠 17-22 周）的脑切片中，我们评估了丘脑的内背侧核（MD）、中央正中核（CM）和旁正中核（PF）中的细胞密度，以及第三脑室中增殖细胞的密度。
我们发现这三个核都有明显的细胞密度降低。这种缺陷与第三脑室中增殖细胞密度降低有关，表明 DS 胎儿 MD、CM 和 PF 的细胞减少是由于神经发生受损所致。对 MD、CM 和 PF 中的投射神经元和中间神经元进行单独评估表明，DS 胎儿的投射神经元密度降低，而中间神经元密度没有变化。
本研究为 DS 相关的 MD、CM 和 PF 细胞密度改变提供了新的证据，并表明这些核中信号处理的改变可能与 DS 患者从婴儿期开始出现的高级控制过程损伤有关。
