title: BDNF-, IGF-1- and GDNF-secreting human neural progenitor cells rescue amyloid β-induced toxicity in cultured rat septal neurons.
abstract: Alzheimer's disease (AD) is characterized by the depositions of amyloid-β (Aβ) 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 Aβ(1-42) peptide. Oligomeric Aβ(1-42), (10 μM) 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 Aβ(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.
authors: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand.
authors: Narisorn
authors: N
authors: Kitiyanant
authors: Yindee
authors: Y
authors: Kitiyanant
authors: Clive N
authors: CN
authors: Svendsen
authors: Wipawan
authors: W
authors: Thangnipon
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D020665:Septum of Brain / Q000166:cytology / Q000187:drug effects*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D007334:Insulin-Like Growth Factor I; D002795:Choline O-Acetyltransferase