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BDNF-, IGF-1- and GDNF-Secreting Human Neural Progenitor Cells Rescue Amyloid β-Induced Toxicity in Cultured Rat Septal Neurons

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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 Aβ1-42 peptide. Oligomeric Aβ1-42, (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 Aβ1-42 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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Acknowledgments

We thank the Office of the Higher Education Commission, Thailand, for providing grant funds via the Strategic Scholarships for Frontier Research Network for the Joint Ph.D. Program Thai Doctoral Degree for NK. This work was partially supported by Mahidol University, grant no. 02011868-0004. We are thankful to Masatoshi Suzuki and Craig Atwood at the University of Wisconsin-Madison, USA for their advice on experimental techniques and Prof. Prapon Wilairat for his critical reading in the manuscript.

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Authors and Affiliations

  1. Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand

    Narisorn Kitiyanant & Wipawan Thangnipon

  2. Reproductive and Stem Cell Biology Research Group, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand

    Narisorn Kitiyanant & Yindee Kitiyanant

  3. Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Yindee Kitiyanant

  4. Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Clive N. Svendsen

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  1. Narisorn Kitiyanant
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  2. Yindee Kitiyanant
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  3. Clive N. Svendsen
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  4. Wipawan Thangnipon
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Correspondence to Wipawan Thangnipon.

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Kitiyanant, N., Kitiyanant, Y., Svendsen, C.N. et al. BDNF-, IGF-1- and GDNF-Secreting Human Neural Progenitor Cells Rescue Amyloid β-Induced Toxicity in Cultured Rat Septal Neurons. Neurochem Res 37, 143–152 (2012). https://doi.org/10.1007/s11064-011-0592-1

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  • DOI: https://doi.org/10.1007/s11064-011-0592-1

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