Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition

Emily A. Meyers*, Kevin T. Gobeske, Allison M. Bond, Jennifer C. Jarrett, Chian-Yu Peng, John Kessler

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition.

Original languageEnglish (US)
Pages (from-to)164-175
Number of pages12
JournalNeurobiology of Aging
Volume38
DOIs
StatePublished - Jan 1 2016

Fingerprint

Bone Morphogenetic Proteins
Neurogenesis
Cognition
Bone Morphogenetic Protein 4
Dentate Gyrus
Hippocampus
Inhibition (Psychology)

Keywords

  • Aging
  • Dentate gyrus
  • Environmental enrichment
  • Neural stem cell
  • Novel object recognition

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Meyers, Emily A. ; Gobeske, Kevin T. ; Bond, Allison M. ; Jarrett, Jennifer C. ; Peng, Chian-Yu ; Kessler, John. / Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition. In: Neurobiology of Aging. 2016 ; Vol. 38. pp. 164-175.
@article{ffd4fc9ff62c4c3f872cbe0ef073ab2e,
title = "Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition",
abstract = "Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition.",
keywords = "Aging, Dentate gyrus, Environmental enrichment, Neural stem cell, Novel object recognition",
author = "Meyers, {Emily A.} and Gobeske, {Kevin T.} and Bond, {Allison M.} and Jarrett, {Jennifer C.} and Chian-Yu Peng and John Kessler",
year = "2016",
month = "1",
day = "1",
doi = "10.1016/j.neurobiolaging.2015.10.035",
language = "English (US)",
volume = "38",
pages = "164--175",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",

}

Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition. / Meyers, Emily A.; Gobeske, Kevin T.; Bond, Allison M.; Jarrett, Jennifer C.; Peng, Chian-Yu; Kessler, John.

In: Neurobiology of Aging, Vol. 38, 01.01.2016, p. 164-175.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition

AU - Meyers, Emily A.

AU - Gobeske, Kevin T.

AU - Bond, Allison M.

AU - Jarrett, Jennifer C.

AU - Peng, Chian-Yu

AU - Kessler, John

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition.

AB - Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition.

KW - Aging

KW - Dentate gyrus

KW - Environmental enrichment

KW - Neural stem cell

KW - Novel object recognition

UR - http://www.scopus.com/inward/record.url?scp=84962255245&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962255245&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2015.10.035

DO - 10.1016/j.neurobiolaging.2015.10.035

M3 - Article

VL - 38

SP - 164

EP - 175

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -