A Critical Period in Cortical Interneuron Neurogenesis in Down Syndrome Revealed by Human Neural Progenitor Cells
Open accessAbstract
Down syndrome (DS) is a developmental disorder whose mental impairment is due to defective cortical development. Human neural progenitor cells (hNPCs) derived from fetal DS cortex initially produce normal numbers of neurons, but generate fewer neurons with time in culture, similar to the pattern of neurogenesis that occurs in DS in vivo. Microarray analysis of DS hNPCs at this critical time reveals gene changes indicative of defects in interneuron progenitor development. In addition, dysregulated expression of many genes involved in neural progenitor cell biology points to changes in the progenitor population and subsequent reduction in interneuron neurogenesis. Delineation of a critical period in interneuron development in DS provides a foundation for investigation of the basis of reduced neurogenesis in DS and defines a time when these progenitor cells may be amenable to therapeutic treatment.
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Neurospheres derived from individuals with Down syndrome expand more slowly than those from controls, suggesting that they contain fewer proliferating progenitor cells.
“Neurospheres derived from individuals with DS expand more slowly than those from controls, suggesting that they contain fewer proliferating progenitor cells.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [68]
In “Temporal Changes in Neurogenesis from Trisomy 21 hNPCs,” the paper reports slower growth of trisomy 21 neurospheres and suggests a loss of progenitor cells. It does not establish that fewer of those cells were proliferating: Ki67 measurements found no significant difference in cell division compared with controls. (LLM, conf=0.87)
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- Authors
- Bhattacharyya, A., McMillan, E., Chen, S. I., Wallace, K., & Svendsen, C. N.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Developmental Neuroscience
- Publisher
- S. Karger AG
- Published
- 2009
- Volume
- 31
- Issue
- 6
- Pages
- 497-510
- ISSN
- 0378-5866 (ISSN-L)
- 1421-9859
- PMC
- PMC2818457
- OpenAlex
- W1986295842
- Cited by
- 79
- References
- 6
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 9 · 2021: 2 · 2020: 8 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Developmental Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Down Syndrome Society
- Waisman Center (P30 HD03352, HD03352)
- National Institute of Child Health and Human Development (P30HD03352, HD03352)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD03352., P30HD003352)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Down syndrome, cortical development, human neural progenitor cells, critical period, gene expression dysregulation, fetal cortex
- MeSH terms
- Cell Count, Cells, Cultured, Cerebral Cortex, Down Syndrome, Fetus, Fluorescent Antibody Technique, gamma-Aminobutyric Acid, Humans, Interneurons, Time Factors, Gene Expression, Cell Death, Glutamic Acid, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Multipotent Stem Cells, Vesicular Inhibitory Amino Acid Transport Proteins, Vesicular Glutamate Transport Protein 1, Neurogenesis
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