Early postnatal defects in neurogenesis in the 3xTg mouse model of Alzheimer’s disease

Liu, Yubing, Bilen, Maria, McNicoll, Marie Michelle, Harris, Richard A., Fong, Bensun C., Iqbal, Mohamed Ariff, Paul, Smitha, Mayne, Janice, Walker, Krystal, Wang, Jing, Figeys, Daniel and Slack, Ruth S. (2023) Early postnatal defects in neurogenesis in the 3xTg mouse model of Alzheimer’s disease. Cell Death and Disease, 14 (2). ISSN 2041-4889

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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to dementia. The hippocampus, which is one of the sites where neural stem cells reside and new neurons are born, exhibits the most significant neuronal loss in AD. A decline in adult neurogenesis has been described in several animal models of AD. However, the age at which this defect first appears remains unknown. To determine at which stage, from birth to adulthood, the neurogenic deficits are found in AD, we used the triple transgenic mouse model of AD (3xTg). We show that defects in neurogenesis are present as early as postnatal stages, well before the onset of any neuropathology or behavioral deficits. We also show that 3xTg mice have significantly fewer neural stem/progenitor cells, with reduced proliferation and decreased numbers of newborn neurons at postnatal stages, consistent with reduced volumes of hippocampal structures. To determine whether there are early changes in the molecular signatures of neural stem/progenitor cells, we perform bulk RNA-seq on cells sorted directly from the hippocampus. We show significant changes in the gene expression profiles at one month of age, including genes of the Notch and Wnt pathways. These findings reveal impairments in neurogenesis very early in the 3xTg AD model, which provides new opportunities for early diagnosis and therapeutic interventions to prevent neurodegeneration in AD.

Item Type:	Article
Additional Information:	The authors thank Guohua Li for excellent technical assistance in animal colony maintenance. We thank Fernando Ortiz for the technical assistance during YFP sorting and the Imaging Core Facility in the Faculty of Medicine. We also thank TCAG Facilities in SickKids for performing RNA-seq. Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41419-023-05650-1
Uncontrolled Keywords:	immunology,cellular and molecular neuroscience,cell biology,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2403
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	06 Mar 2026 17:30
Last Modified:	09 Mar 2026 16:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102249
DOI:	10.1038/s41419-023-05650-1

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