期刊
NEUROCHEMICAL RESEARCH
卷 37, 期 1, 页码 143-152出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-011-0592-1
关键词
Amyloid-beta; Neurotrophic factors; Neural progenitor cells; Septal neurons; Choline acetyltransferase
资金
- Office of the Higher Education Commission, Thailand
- Mahidol University [02011868-0004]
Alzheimer's disease (AD) is characterized by the depositions of amyloid-beta (A beta) proteins, resulting in a reduction of choline acetyltransferase (ChAT) activity of AD brain in the early stages of the disease. Several growth factors, including brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF)-1 and glial cell-derived neurotrophic factor (GDNF) are known to protect neuronal cell death in several neurodegenerative both in vitro and in vivo models. In this study, septal neurons were prepared from septal nucleus of embryonic (day 16-17) rat brain and treated with monomeric, oligomeric or fibrillar A beta(1-42) peptide. Oligomeric A beta(1-42), (10 mu M) was the most potent at sublethal dose. Septal neuron cultures treated with BDNF, IGF-1 or GDNF or co-cultured with genetically modified human neural progenitor cells (hNPCs) secreting these neurotrophic factors (but not allowing contact between the two cell types), were protected from oligomeric A beta(1-42) peptide-induced cell death, and these trophic factors enhanced cholinergic functions by increasing ChAT expression level. These results indicate the potential of employing transplanted hNPCs for treatment of AD.
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