PMID- 26297896 OWN - NLM STAT- MEDLINE DCOM- 20160706 LR - 20181202 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 307 DP - 2015 Oct 29 TI - In vitro validation of effects of BDNF-expressing mesenchymal stem cells on neurodegeneration in primary cultured neurons of APP/PS1 mice. PG - 37-50 LID - S0306-4522(15)00734-4 [pii] LID - 10.1016/j.neuroscience.2015.08.011 [doi] AB - Alzheimer's disease (AD), the most common type of dementia, is characterized by the presence of senile plaques, neurofibrillary tangles, and neuronal loss in defined regions of the brain including the hippocampus and cortex. Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) offers a safe and potentially effective tool for treating neurodegenerative disorders. However, the therapeutic effects of BM-MSCs on AD pathology remain unclear and their mechanisms at cellular and molecular levels still need to be addressed. In this study, we developed a unique neuronal culture made from 5xFAD mouse, an APP/PS1 transgenic mouse model (FAD neurons) to investigate progressive neurodegeneration associated with AD pathology and efficacy of brain-derived neurotrophic factor expressing-MSCs (BDNF-MSCs). Analyses of the expression of brain-derived neurotrophic factor (BDNF), synaptic markers and survival/apoptotic signals indicate that pathological features of cultured neurons made from these mice accurately mimic AD pathology, suggesting that our protocol provided a valid in vitro model of AD. We also demonstrated amelioration of AD pathology by MSCs in vitro when these FAD neurons were co-cultured with MSCs, a paradigm that mimics the in vivo environment of post-transplantation of MSCs into damaged regions of brains. To overcome failed delivery of BDNF to the brain and to enhance MSCs releasing BDNF effect, we created BDNF-MSCs and found that MSCs protection was enhanced by BDNF-MSCs. This protection was abolished by BDNF-blocking peptides, suggesting that BDNF supply from BDNF-MSCs was enough to prevent AD pathology. CI - Copyright (c) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Song, M-S AU - Song MS AD - Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI, USA; Program of Neuroscience, Central Michigan University, Mt Pleasant, MI, USA. Electronic address: song5m@cmich.edu. FAU - Learman, C R AU - Learman CR AD - Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI, USA; Program of Neuroscience, Central Michigan University, Mt Pleasant, MI, USA. FAU - Ahn, K-C AU - Ahn KC AD - Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. FAU - Baker, G B AU - Baker GB AD - Neurochemical Research Unit, University of Alberta, AB, Canada. FAU - Kippe, J AU - Kippe J AD - Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI, USA; Program of Neuroscience, Central Michigan University, Mt Pleasant, MI, USA. FAU - Field, E M AU - Field EM AD - Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI, USA. FAU - Dunbar, G L AU - Dunbar GL AD - Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI, USA; Program of Neuroscience, Central Michigan University, Mt Pleasant, MI, USA. Electronic address: dunba1g@cmich.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150820 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 0 (Presenilin-1) RN - 0 (presenilin 1, mouse) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Alzheimer Disease/*complications/genetics/pathology MH - Amyloid beta-Protein Precursor/genetics MH - Animals MH - Apoptosis/genetics MH - Brain/cytology/metabolism/pathology MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Caspase 3/metabolism MH - Cells, Cultured MH - Coculture Techniques MH - Disease Models, Animal MH - Female MH - Male MH - Mesenchymal Stem Cells/*physiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Mutation/genetics MH - Nerve Tissue Proteins/metabolism MH - Neurodegenerative Diseases/*etiology/*pathology MH - Neurons/metabolism MH - Presenilin-1/genetics OTO - NOTNLM OT - Alzheimer's disease OT - bone marrow-derived mesenchymal cells (BM-MSCs) OT - brain-derived neurotropic factor (BDNF) OT - neurodegeneration OT - beta-amyloid (Abeta) EDAT- 2015/08/25 06:00 MHDA- 2016/07/07 06:00 CRDT- 2015/08/23 06:00 PHST- 2015/06/05 00:00 [received] PHST- 2015/07/23 00:00 [revised] PHST- 2015/08/05 00:00 [accepted] PHST- 2015/08/23 06:00 [entrez] PHST- 2015/08/25 06:00 [pubmed] PHST- 2016/07/07 06:00 [medline] AID - S0306-4522(15)00734-4 [pii] AID - 10.1016/j.neuroscience.2015.08.011 [doi] PST - ppublish SO - Neuroscience. 2015 Oct 29;307:37-50. doi: 10.1016/j.neuroscience.2015.08.011. Epub 2015 Aug 20.