title: Recovery from experimental parkinsonism by intrastriatal application of erythropoietin or EPO-releasing neural precursors.
abstract: An extensive literature has shown a powerful neuroprotective action of Erythropoietin (EPO) both in vivo and in vitro. This study shows that EPO, whether ectopically administered or released by neural precursors, does reverse MPTP-induced parkinsonism in mice. Unilateral stereotaxic injection of 2.5 × 105erythropoietin-releasing neural precursor cells (Er-NPCs) rescued degenerating striatal dopaminergic neurons and promoted behavioral recovery as shown by three independent behavioral tests. These effects were replicated through direct intrastriatal administration of recombinant human EPO. At the end of the observational period, most of the transplanted Er-NPCs were vital and migrated via the striatum to reach Substantia Nigra. The restorative effects appear to be mediated by EPO since co-injection of anti-EPO or anti-EPOR antibodies antagonized the positive outcomes. Furthermore, this report supports the neuroprotective action of EPO, which may also be achieved via administration of EPO-releasing cells such as Er-NPCs.
authors.affiliation: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy. Electronic address: stephana.carelli@guest.unimi.it.
authors.forename: Stephana
authors.initials: S
authors.lastname: Carelli
authors.affiliation: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Toniella
authors.initials: T
authors.lastname: Giallongo
authors.affiliation: Dipartimento di Ricerca Traslazionale e Delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Viaggi
authors.affiliation: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Latorre
authors.affiliation: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Gombalova
authors.affiliation: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Raspa
authors.affiliation: Experimental Oncology Department, European Institute of Oncology, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mazza
authors.affiliation: Dipartimento di Ricerca Traslazionale e Delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vaglini
authors.affiliation: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giulio
authors.affiliation: Laboratories of Pharmacology, Department of Health Sciences, University of Milan, Milan, Italy. Electronic address: alfredo.gorio@unimi.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gorio
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D029681:Arabidopsis Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019751:Intramolecular Transferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000601:surgery; D020127:Recovery of Function / Q000187:drug effects*; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D029681:Arabidopsis Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D004921:Erythropoietin; D049452:Green Fluorescent Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D019751:Intramolecular Transferases; C568454:marneral synthase, Arabidopsis
keywords: Adult stem cells; Cell therapy; Erythropoietin; MPTP; Parkinson's disease; Regenerative medicine