title: Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem cell grafts in an APP transgenic model of Alzheimer disease.
abstract: 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.
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Rockenstein
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Desplats
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Kiren
authors.initials: K
authors.lastname: Ubhi
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mante
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Jazmin
authors.initials: J
authors.lastname: Florio
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: Clinical Research & Pharmacology, EVER Neuro Pharma GmbH, Unterach, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.affiliation: Clinical Research & Pharmacology, EVER Neuro Pharma GmbH, Unterach, Austria.
authors.forename: Hemma
authors.initials: H
authors.lastname: Brandstaetter
authors.affiliation: Clinical Research & Pharmacology, EVER Neuro Pharma GmbH, Unterach, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Meier
authors.affiliation: 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.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000628:therapy*; D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use*; D016229:Amyloid beta-Peptides / Q000235:genetics*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D045683:Furin / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation*; D055495:Neurogenesis / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009414:Nerve Growth Factors; D009479:Neuropeptides; C006952:cerebrolysin; D045683:Furin; D001973:Bromodeoxyuridine