title: Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease.
abstract: Degeneration of the nigrostriatal dopaminergic pathway, the hallmark of Parkinson's disease, can be recapitulated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. Herein, we demonstrate that adoptive transfer of copolymer-1 immune cells to MPTP recipient mice leads to T cell accumulation within the substantia nigra pars compacta, suppression of microglial activation, and increased local expression of astrocyte-associated glial cell line-derived neurotrophic factor. This immunization strategy resulted in significant protection of nigrostriatal neurons against MPTP-induced neurodegeneration that was abrogated by depletion of donor T cells. Such vaccine treatment strategies may provide benefit for Parkinson's disease.
authors.affiliation: Center for Neurovirology and Neurodegenerative Disorders and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Benner
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Destache
authors.forename: Travis B
authors.initials: TB
authors.lastname: Lewis
authors.forename: Vernice
authors.initials: V
authors.lastname: Jackson-Lewis
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.forename: Craig
authors.initials: C
authors.lastname: Nemachek
authors.forename: Steven R
authors.initials: SR
authors.lastname: Green
authors.forename: Serge
authors.initials: S
authors.lastname: Przedborski
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019264:Adoptive Transfer; D000818:Animals; D020755:Coat Protein Complex I / Q000276:immunology*; D003342:Corpus Striatum / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004298:Dopamine / Q000276:immunology*; D007150:Immunohistochemistry; D008636:Mesencephalon / Q000276:immunology* / Q000473:pathology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009474:Neurons / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000276:immunology / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D020755:Coat Protein Complex I; D016207:Cytokines; D010047:Ovalbumin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine