Anita Bhattacharyya, PhD – Slide of the Week

Anita Bhattacharyya, PhD - Slide of the Week

Title: Meta-Analysis of Down Syndrome Cortical Development Reveals Underdeveloped State of the Science

Legend: The appearance of cognitive deficits in infancy in Down syndrome suggests that alterations emerge during the earliest stages of brain development. Neural correlates of intellectual and language function include cortical structures, specifically temporal and frontal lobes, are smaller in Down syndrome at birth. We carried out a systematic review of published research on cortical development in Down syndrome to identify publications that provide information on differences in cell numbers or cell structures that may inform the gross difference in brain structure. We assessed 115 published reports retrieved through PubMed and other sources and found that only 23 reported histological and/or immunohistochemical data to define cell composition affected in Down syndrome post-mortem brain (A, B). Our analysis reveals that many reports have limited samples sizes and few DS samples (C), making it difficult to draw conclusions that are generally applicable to the DS population. Our analysis reveals a paucity of studies that rigorously assess cell types in the developing Down syndrome brain.

Citation: Risgaard, K. A., Sorci, I. A., Mohan, S., & Bhattacharyya, A. (2022). Meta-Analysis of Down Syndrome Cortical Development Reveals Underdeveloped State of the Science. Frontiers in cellular neuroscience, 16, 915272. https://doi.org/10.3389/fncel.2022.915272

Abstract: Neurodevelopmental impairment contributes to the hallmark cognitive disability in individuals with Down syndrome (DS, trisomy 21, T21). The appearance of cognitive deficits in infancy suggests that alterations emerge during the earliest stages of neural development and continue throughout the lifespan in DS. Neural correlates of intellectual and language function include cortical structures, specifically temporal and frontal lobes that are smaller in DS. Yet, despite increased understanding of the DS cognitive-behavioral phenotype in childhood, there is very little structural and histological information to help explain the deficits. Consequently, attempts to effectively design therapeutic targets or interventions are limited. We present a systematic review of published research on cortical development in DS that reveals a paucity of studies that rigorously identify cellular features that may underlie the gross morphological deficits of the developing DS brain. We assessed 115 published reports retrieved through PubMed and other sources and found that only 23 reported histological and/or immunohistochemical data to define cell composition affected in DS post-mortem brain. Further, our analysis reveals that many reports have limited samples sizes and few DS samples, making it difficult to draw conclusions that are generally applicable to the DS population. Thus, the lack of replication and limited number of studies indicate that more developmentally focused research, ideally using equal numbers of age-matched samples in analyses, is needed to elucidate the cellular nature of smaller brain size in DS. 

About the Lab: Anita Bhattacharyya’s lab examines how brain development is altered in developmental disorders characterized by intellectual impairment. The cerebral cortex is the most complex area of the brain and is responsible for functions unique to humans, such as language and abstract thought. Problems in any of the crucial cerebral cortex formation steps can lead to intellectual impairment.

Investigator: Anita Bhattacharyya, PhD

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