Brain Development in Down Syndrome during Fetal, Newborn, and Infant Stages

胎儿、新生儿和婴儿阶段唐氏综合症的大脑发育

• 批准号: 10507226
• 负责人: Emi Takahashi (Oki)
• 金额: $ 5.41万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10507226
• 关键词: Brain; Development; Down; Syndrome; during

Abstract Down syndrome (DS), known as trisomy 21, is the most common chromosomal disorder in newborns. The number of babies born with DS is increasing, with about 1 in every 700 babies being born with DS in the United States (US). Patients with DS carry an extra complete or partial chromosome 21, disrupting numerous processes, including cardiac, digestive, and neural systems, with cognitive impairment being one of the most notable features. Patients with DS have problems with learning, memory, and speech/language throughout life, as well as an early onset of Alzheimer’s disease. Given that DS patients live longer than before as a result of improved medical care, and in view of the fact that the concept of locus minoris resistentiae is still valid, it is critical to study the altered initial states of brain development in DS for the purpose of better predicting what aspects of brain function will preferentially and precociously deteriorate; this would allow for earlier and better prevention and treatment. However, detailed, comprehensive knowledge of early development of cortical anatomy and fiber pathways in DS patients is still lacking. The brain abnormalities in DS begin in utero; fewer neurons are generated and migrate to wrong destinations. By 15 gestational weeks (GW), brains with DS have abnormal cortical thickness, with volumes that are 80% of those of typically developing brains. However, much more detailed information is needed, and we now have the tools to make direct anatomical observation on fetal and early postnatal DS brains. We have extensive experience, both in ex vivo and in vivo, magnetic resonance imaging (MRI) of human brains. We have established that high-angular resolution diffusion MRI (HARDI) with optimal parameters has the potential to define the connectional anatomy of developing human fetal, newborn, and infant brains. We have reported, with unprecedented details, spatiotemporal developmental patterns of the majority of axonal tracts, as well as regional regression patterns of neuronal migration pathways using diffusion MRI tractography. In fetal ages, transient zones (e.g., future cortical gray matter, cortical plate [CP]; future white matter, intermediate zone [IZ]) continuously change their morphology, reflecting neuronal proliferation/migration, and axonal elongation, maturation, and pruning, and could provide critical biomarkers for normal/abnormal brain development. Through recent preliminary MRI investigations in typically developing brains, we have observed migration and axonal pathways terminating in different transient zones, not randomly but with unique spatiotemporal patterns. Based on the demonstrated anomalies in the gross morphology of the DS brain, together with what is already known about metric changes in the cortex and white matter, we hypothesize that early brain development in DS will show regionally differential spatiotemporal patterns as compared to that in controls.

摘要 唐氏综合征（DS），即21三体综合征，是新生儿中最常见的染色体异常。的 出生时患有DS的婴儿数量正在增加，美国每700名婴儿中就有1名出生时患有DS 美国。DS患者携带额外的完整或部分21号染色体，破坏了许多 过程，包括心脏，消化和神经系统，认知障碍是其中一个最重要的 显著特征。患有DS的患者在一生中都有学习、记忆和言语/语言方面的问题， 以及阿尔茨海默病的早期发作。由于DS患者的寿命比以前长， 改善医疗保健，并鉴于这一事实，即小抵抗力的概念仍然是有效的，它是 研究DS中大脑发育的改变的初始状态是至关重要的，目的是更好地预测 大脑功能的各个方面将优先和早熟地恶化;这将允许更早和更好地 预防和治疗。然而，详细，全面的知识，早期发展的皮质 解剖学和纤维通路在DS患者中仍然缺乏。DS的大脑异常开始于子宫内; 神经元被生成并迁移到错误的目的地。到15孕周（GW），患有DS的大脑 皮质厚度异常，体积是正常发育大脑的80%。然而，许多 需要更详细的信息，我们现在有工具对胎儿进行直接解剖观察。 和出生后早期的DS大脑。我们在体外和体内都有丰富的经验， 核磁共振成像（MRI）。我们已经确定高角分辨率弥散MRI （HARDI）具有最佳参数，有可能定义发育中人类的连接解剖学 胎儿、新生儿和婴儿的大脑。我们以前所未有的细节报道了 大多数轴突束的模式，以及神经元迁移途径的区域回归模式 使用弥散磁共振纤维束成像。在胎儿期，瞬时区（例如，未来皮质灰质，皮质板 [CP];未来的白色物质，中间区[IZ]）不断改变其形态，反映神经元 增殖/迁移，轴突伸长，成熟和修剪，并可以提供关键的生物标志物， 正常/异常的大脑发育。通过最近对典型发展中国家的初步MRI研究， 在大脑中，我们观察到迁移和轴突通路终止于不同的瞬态区，而不是随机的 但有独特的时空模式根据所证明的大体形态异常， DS大脑，连同已经知道的皮质和白色物质的度量变化，我们 假设DS早期脑发育将显示区域差异时空模式， 与对照组相比。

项目成果

Quantitative analyses of high-angular resolution diffusion imaging (HARDI)-derived long association fibers in children with sensorineural hearing loss.

• DOI: 10.1002/jdn.10071
• 发表时间: 2020-12
• 期刊: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
• 作者: Shiohama T;Chew B;Levman J;Takahashi E
• 通讯作者: Takahashi E

Structural abnormalities in paediatric moyamoya disease revealed by clinical magnetic resonance imaging, regionally distributed relative signal intensities and volumes.

• DOI: 10.1002/jdn.10167
• 发表时间: 2022-04
• 期刊: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
• 作者: Ijner P;Tompkins G;Shiohama T;Takahashi E;Levman J
• 通讯作者: Levman J

Clinically detectable structural abnormalities in pediatric-onset multiple sclerosis: A large-scale magnetic resonance imaging analysis.

儿科发病的多发性硬化症临床可检测的结构异常：大规模磁共振成像分析。

• DOI: 10.1002/jdn.10090
• 发表时间: 2021
• 期刊: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
• 作者: Levman,Jacob;Das,Avilash;MacDonald,Allissa;MacDonald,Patrick;Berrigan,Lindsay;Takahashi,Emi
• 通讯作者: Takahashi,Emi

Structural magnetic resonance imaging demonstrates volumetric brain abnormalities in down syndrome: Newborns to young adults.

• DOI: 10.1016/j.nicl.2021.102815
• 发表时间: 2021
• 期刊: NeuroImage. Clinical
• 作者: McCann B;Levman J;Baumer N;Lam MY;Shiohama T;Cogger L;MacDonald A;Ijner P;Takahashi E
• 通讯作者: Takahashi E

Magnetic resonance imaging demonstrates gyral abnormalities in Tourette syndrome.

磁共振成像显示抽动秽语综合症的脑回异常。

• DOI: 10.1002/jdn.10209
• 发表时间: 2022
• 期刊: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
• 作者: McCann,Bernadette;Lam,MelanieY;Shiohama,Tadashi;Ijner,Prahar;Takahashi,Emi;Levman,Jacob
• 通讯作者: Levman,Jacob