دورية أكاديمية
أعرض في EDS

Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis.

التفاصيل البيبلوغرافية
العنوان: Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis.
المؤلفون: Crews L; Departments of Neurosciences and Pathology, University of California, San Diego, La Jolla, California 92093-0624., Adame A, Patrick C, Delaney A, Pham E, Rockenstein E, Hansen L, Masliah E
المصدر: The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2010 Sep 15; Vol. 30 (37), pp. 12252-62.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington, DC : Society for Neuroscience
Original Publication: [Baltimore, Md.] : The Society, c1981-
مواضيع طبية MeSH: Brain Chemistry*/genetics , Neurogenesis*/genetics, Alzheimer Disease/*metabolism , Amyloid beta-Protein Precursor/*genetics , Bone Morphogenetic Protein 6/*biosynthesis , Bone Morphogenetic Protein 6/*genetics , Neural Inhibition/*genetics , Up-Regulation/*genetics, Aged, 80 and over ; Alzheimer Disease/genetics ; Alzheimer Disease/physiopathology ; Amyloid beta-Protein Precursor/physiology ; Animals ; Bone Morphogenetic Protein 6/physiology ; Disease Models, Animal ; Female ; Humans ; Male ; Mice
مستخلص: During aging and in the progression of Alzheimer's disease (AD), synaptic plasticity and neuronal integrity are disturbed. In addition to the alterations in plasticity in mature neurons, the neurodegenerative process in AD has been shown to be accompanied by alterations in neurogenesis. Members of the bone morphogenetic protein (BMP) family of growth factors have been implicated as important regulators of neurogenesis and neuronal cell fate determination during development; however, their role in adult neurogenesis and in AD is less clear. We show here by qRT-PCR analysis that BMP6 mRNA levels were significantly increased in the hippocampus of human patients with AD and in APP transgenic mice compared to controls. Immunoblot and immunohistochemical analyses confirmed that BMP6 protein levels were increased in human AD brains and APP transgenic mouse brains compared to controls and accumulated around hippocampal plaques. The increased levels of BMP6 were accompanied by defects in hippocampal neurogenesis in AD patients and APP transgenic mice. In support of a role for BMP6 in defective neurogenesis in AD, we show in an in vitro model of adult neurogenesis that treatment with amyloid-β(1-42) protein (Aβ) resulted in increased expression of BMP6, and that exposure to recombinant BMP6 resulted in reduced proliferation with no toxic effects. Together, these results suggest that Aβ-associated increases in BMP6 expression in AD may have deleterious effects on neurogenesis in the hippocampus, and therapeutic approaches could focus on normalization of BMP6 levels to protect against AD-related neurogenic deficits.
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معلومات مُعتمدة: AG11385 United States AG NIA NIH HHS; R01 AG011385 United States AG NIA NIH HHS; R37 AG018440-10 United States AG NIA NIH HHS; P50 AG005131 United States AG NIA NIH HHS; P01 AG022074-080009 United States AG NIA NIH HHS; R01 AG018440 United States AG NIA NIH HHS; R37 AG018440 United States AG NIA NIH HHS; P50 AG005131-190023 United States AG NIA NIH HHS; R37 AG011385 United States AG NIA NIH HHS; AG5131 United States AG NIA NIH HHS; AG022074 United States AG NIA NIH HHS; R37 AG011385-16 United States AG NIA NIH HHS; AG18440 United States AG NIA NIH HHS; P01 AG022074 United States AG NIA NIH HHS
المشرفين على المادة: 0 (Amyloid beta-Protein Precursor)
0 (BMP6 protein, human)
0 (Bone Morphogenetic Protein 6)
تواريخ الأحداث: Date Created: 20100917 Date Completed: 20101025 Latest Revision: 20220330
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC2978735
DOI: 10.1523/JNEUROSCI.1305-10.2010
PMID: 20844121
قاعدة البيانات: MEDLINE
الوصف
تدمد:1529-2401
DOI:10.1523/JNEUROSCI.1305-10.2010