Proliferation, differentiation and amyloid-β production in neural progenitor cells isolated from TgCRND8 mice

Neuroscience
S KanemotoP E Fraser

Abstract

The amyloid precursor protein (APP) and amyloid-β (Aβ) peptide play central roles in the pathology and etiology of Alzheimer's disease. Amyloid-induced impairments in neurogenesis have been investigated in several transgenic mouse models but the mechanism of action remains to be conclusively demonstrated. The changes in neurogenesis during this transition of increasing Aβ levels and plaque formation were investigated in the present study. We found that the proliferation of newborn cell in the dentate gyrus was enhanced prior to elevations in soluble Aβ production as well as amyloid deposition in 5-week-old TgCRND8 mice, which are well-established Alzheimer's disease models, compared to non-transgenic (Non-Tg) mice. The number of BrdU-positive cells remained higher in TgCRND8 vs Non-Tg mice for a period of 8weeks. The numbers of BrdU/NeuN-positive cells were not significantly different in TgCRND8 compared to Non-Tg mice. A significant decrease in BrdU/GFAP but not in BrdU/S100β was found in Tg vs Non-Tg at 6-weeks of age. In addition, a unique observation was made using isolated neuroprogenitor cells from TgCRND8 mice which were found to be less viable in culture and produced substantial amounts of secreted Aβ peptides. This sug...Continue Reading

References

Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·G GheusiP M Lledo
Feb 26, 2000·Science·F H Gage
Nov 18, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sanjay S P MagaviJeffrey D Macklis
Dec 15, 2007·Nature Protocols·Nohjin KeePaul W Frankland
Oct 30, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wei DengFred H Gage

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Citations

Apr 18, 2015·Stem Cell Research & Therapy·Steven J CollinsCathryn L Haigh
Jun 23, 2016·Cell Biochemistry and Biophysics·Cathryn L HaighSimon C Drew
Sep 1, 2017·Scientific Reports·David Baglietto-VargasAntonia Gutierrez
Mar 23, 2018·Neurogenesis·Oliver Wirths
Aug 6, 2019·Frontiers in Cell and Developmental Biology·Sabrina PicocciGianfranco Gennarini
Dec 11, 2020·Neurobiology of Disease·Michele Longoni CalióMarimélia Aparecida Porcionatto
Feb 9, 2021·Mechanisms of Ageing and Development·Hang LiuYing Ma

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Methods Mentioned

BETA
fluorescence microscopy
enzyme-linked immunoabsorbent assay
ELISA
transgenic
transgenics

Software Mentioned

Prism

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