PMID- 26209890 OWN - NLM STAT- MEDLINE DCOM- 20160425 LR - 20211203 IS - 1876-7753 (Electronic) IS - 1873-5061 (Linking) VI - 15 IP - 1 DP - 2015 Jul TI - Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem cell grafts in an APP transgenic model of Alzheimer disease. PG - 54-67 LID - S1873-5061(15)00050-1 [pii] LID - 10.1016/j.scr.2015.04.008 [doi] AB - Neural stem cells (NSCs) have been considered as potential therapy in Alzheimer's disease (AD) but their use is hampered by the poor survival of grafted cells. Supply of neurotrophic factors to the grafted cells has been proposed as a way to augment survival of the stem cells. In this context, we investigated the utility of Cerebrolysin (CBL), a peptidergic mixture with neurotrophic-like properties, as an adjunct to stem cell therapy in an APP transgenic (tg) model of AD. We grafted murine NSCs into the hippocampus of non-tg and APP tg that were treated systemically with CBL and analyzed after 1, 3, 6 and 9months post grafting. Compared to vehicle-treated non-tg mice, in the vehicle-treated APP tg mice there was considerable reduction in the survival of the grafted NSCs. Whereas, CBL treatment enhanced the survival of NSCs in both non-tg and APP tg with the majority of the surviving NSCs remaining as neuroblasts. The NSCs of the CBL treated mice displayed reduced numbers of caspase-3 and TUNEL positive cells and increased brain derived neurotrophic factor (BDNF) and furin immunoreactivity. These results suggest that CBL might protect grafted NSCs and as such be a potential adjuvant therapy when combined with grafting. CI - Copyright (c) 2015. Published by Elsevier B.V. FAU - Rockenstein, Edward AU - Rockenstein E AD - Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. FAU - Desplats, Paula AU - Desplats P AD - Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. FAU - Ubhi, Kiren AU - Ubhi K AD - Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. FAU - Mante, Michael AU - Mante M AD - Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. FAU - Florio, Jazmin AU - Florio J AD - Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. FAU - Adame, Anthony AU - Adame A AD - Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. FAU - Winter, Stefan AU - Winter S AD - Clinical Research & Pharmacology, EVER Neuro Pharma GmbH, Unterach, Austria. FAU - Brandstaetter, Hemma AU - Brandstaetter H AD - Clinical Research & Pharmacology, EVER Neuro Pharma GmbH, Unterach, Austria. FAU - Meier, Dieter AU - Meier D AD - Clinical Research & Pharmacology, EVER Neuro Pharma GmbH, Unterach, Austria. FAU - Masliah, Eliezer AU - Masliah E AD - Department of Neurosciences, University of California San Diego, La Jolla, CA, USA; Department of Pathology, University of California San Diego, La Jolla, CA, USA. Electronic address: emasliah@ucsd.edu. LA - eng GR - AG05131/AG/NIA NIH HHS/United States GR - AG18440/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150509 PL - England TA - Stem Cell Res JT - Stem cell research JID - 101316957 RN - 0 (Amino Acids) RN - 0 (Amyloid beta-Peptides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Doublecortin Domain Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Mtap2 protein, mouse) RN - 0 (Nerve Growth Factors) RN - 0 (Neuropeptides) RN - 37KZM6S21G (cerebrolysin) RN - EC 3.4.21.75 (Furin) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Alzheimer Disease/pathology/*therapy MH - Amino Acids/pharmacology/*therapeutic use MH - Amyloid beta-Peptides/*genetics MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Bromodeoxyuridine/metabolism MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Disease Models, Animal MH - Doublecortin Domain Proteins MH - Furin/metabolism MH - Hippocampus/drug effects/pathology MH - Humans MH - Immunohistochemistry MH - Mice, Transgenic MH - Microtubule-Associated Proteins/metabolism MH - Neoplasms/pathology MH - Nerve Growth Factors/metabolism MH - Neural Stem Cells/*cytology/drug effects/*transplantation MH - Neurogenesis/drug effects MH - Neuropeptides/metabolism/pharmacology/*therapeutic use EDAT- 2015/07/27 06:00 MHDA- 2016/04/26 06:00 CRDT- 2015/07/27 06:00 PHST- 2014/12/23 00:00 [received] PHST- 2015/03/31 00:00 [revised] PHST- 2015/04/30 00:00 [accepted] PHST- 2015/07/27 06:00 [entrez] PHST- 2015/07/27 06:00 [pubmed] PHST- 2016/04/26 06:00 [medline] AID - S1873-5061(15)00050-1 [pii] AID - 10.1016/j.scr.2015.04.008 [doi] PST - ppublish SO - Stem Cell Res. 2015 Jul;15(1):54-67. doi: 10.1016/j.scr.2015.04.008. Epub 2015 May 9.