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Age-associated increase in BMP signaling inhibits hippocampal neurogenesis.

Yousef, Hanadie, Morgenthaler, Adam, Schlesinger, Christina, Bugaj, Lukasz, Conboy, Irina M., Schaffer, David V.·2015·Stem Cells
DOI 10.1002/stem.1943PMC PMC4818000
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Abstract

Hippocampal neurogenesis, the product of resident neural stem cell proliferation and differentiation, persists into adulthood but decreases with organismal aging, which may contribute to the age-related decline in cognitive function. The mechanisms that underlie this decrease in neurogenesis are not well understood, although evidence in general indicates that extrinsic changes in an aged stem cell niche can contribute to functional decline in old stem cells. Bone morphogenetic protein (BMP) family members are intercellular signaling proteins that regulate stem and progenitor cell quiescence, proliferation, and differentiation in various tissues and are likewise critical regulators of neurogenesis in young adults. Here, we establish that BMP signaling increases significantly in old murine hippocampi and inhibits neural progenitor cell proliferation. Furthermore, direct in vivo attenuation of BMP signaling via genetic and transgenic perturbations in aged mice led to elevated neural stem cell proliferation, and subsequent neurogenesis, in old hippocampi. Such advances in our understanding of mechanisms underlying decreased hippocampal neurogenesis with age may offer targets for the treatment of age-related cognitive decline. Stem Cells 2015;33:1577–1588

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  • Attenuation of TGF-beta signaling in old animals has effects similar to those of NBE.

    “and the fact that attenuation of TGF-beta signaling in old animals has effects that are similar to those of NBE [7, 14, 15, 28, 44].”

    From Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin (2020) · cites this paper as [28]

    The Results section reports that attenuating BMP signaling in aged mice increased hippocampal neural stem-cell proliferation and neurogenesis. The paper identifies this as BMP/pSmad1 signaling, however, and does not compare its effects with NBE or establish the claimed effect for TGF-beta signaling more broadly. No page numbers are available in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Levels of BMP2, 4, 6, and 7 expression increase in the hippocampus and SVZ with age.

    “Levels of BMP2, 4, 6, and 7 expression have been found to increase in the hippocampus and SVZ with age (Yousef et al., 2015; Apostolopoulou et al., 2017).”

    From Inhibiting USP16 rescues stem cell aging and memory in an Alzheimer’s model (2022) · cites this paper as Yousef et al., 2015

    The Results section (‘BMP signaling increases in the aged murine hippocampus’; page unavailable) reports increased Bmp2, Bmp4, and Bmp6 expression in aged mouse hippocampi. It does not report an age-related increase in BMP7 or establish the claimed increases in the SVZ. (LLM, conf=0.90)

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Metadata

Authors
Yousef, H., Morgenthaler, A., Schlesinger, C., Bugaj, L., Conboy, I. M., & Schaffer, D. V.
Affiliations
  • Department of Molecular and Cell Biology, Berkeley, California, USA
  • Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), Berkeley, California, USA
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2015-04-23
Volume
33
Issue
5
Pages
1577-1588
ISSN
  • 1066-5099
  • 1549-4918
DOI
10.1002/stem.1943
PMC
PMC4818000
Cited by
109
References
7
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Funders
  • California Institute for Regenerative Medicine (RT2-02022, NIH R01 NS074831, RN1-00532-1)
  • National Institutes of Health (R01 AG02725201)
  • NSF Graduate Fellowship

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