دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition.
المؤلفون: Meyers EA; Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA. Electronic address: emilymeyers2015@u.northwestern.edu., Gobeske KT; Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA., Bond AM; Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA., Jarrett JC; Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA., Peng CY; Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA., Kessler JA; Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL, USA.
المصدر: Neurobiology of aging [Neurobiol Aging] 2016 Feb; Vol. 38, pp. 164-175. Date of Electronic Publication: 2015 Nov 10.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 8100437 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1558-1497 (Electronic) Linking ISSN: 01974580 NLM ISO Abbreviation: Neurobiol Aging Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Elsevier
Original Publication: Fayetteville, N.Y. : Ankho International.
مواضيع طبية MeSH: Cognition* , Neurogenesis*, Aging/*genetics , Aging/*psychology , Bone Morphogenetic Protein 4/*genetics , Bone Morphogenetic Protein 4/*metabolism , Signal Transduction/*genetics , Signal Transduction/*physiology, Aging/pathology ; Aging/physiology ; Animals ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cognition Disorders/genetics ; Cognition Disorders/therapy ; Dentate Gyrus/metabolism ; Gene Expression ; Hippocampus/pathology ; Hippocampus/physiopathology ; Humans ; Male ; Mice, Inbred C57BL ; Molecular Targeted Therapy
مستخلص: 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.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: P30 AG013854 United States AG NIA NIH HHS; R01 NS020778 United States NS NINDS NIH HHS; T32 GM008152 United States GM NIGMS NIH HHS; NS 20778 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Aging; Dentate gyrus; Environmental enrichment; Neural stem cell; Novel object recognition
المشرفين على المادة: 0 (Bmp4 protein, mouse)
0 (Bone Morphogenetic Protein 4)
0 (Carrier Proteins)
148294-77-3 (noggin protein)
تواريخ الأحداث: Date Created: 20160202 Date Completed: 20161213 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4735642
DOI: 10.1016/j.neurobiolaging.2015.10.035
PMID: 26827654
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-1497
DOI:10.1016/j.neurobiolaging.2015.10.035