Xinyu Zhao, PhD – Slide of the Week

Title: Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of Fragile X Syndrome

Legend: Transient Nutlin-3 treatment of FMR1-deficient mice leads to long lasting gene expression changes and many differentially expressed genes are associated adult neural stem cell niche regulation.

Citation: Sahar Javadi, Yue Li, Jie Sheng, Lucy Zhao, Yao Fu,  Daifeng Wang, and Xinyu Zhao. Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of Fragile X Syndrome. BMC Med 2022 May 13;20(1):163.doi: 10.1186/s12916-022-02370-9. (news release)

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: Located at the Waisman Center of University of Wisconsin-Madison, our laboratory is part of the Department of Neuroscience and Stem Cells and Regenerative Medicine Center.   We strive to adapt, develop, and integrate state-of-art approaches to investigate the molecular mechanisms underlying neurogenesis and neuronal development.

Investigator: Xinyu Zhao, PhD

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