Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease.
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.
Benner
Eric J
EJ
Center for Neurovirology and Neurodegenerative Disorders and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198, USA.
Mosley
R Lee
RL
Destache
Chris J
CJ
Lewis
Travis B
TB
Jackson-Lewis
Vernice
V
Gorantla
Santhi
S
Nemachek
Craig
C
Green
Steven R
SR
Przedborski
Serge
S
Gendelman
Howard E
HE
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
D020755:Coat Protein Complex I; D016207:Cytokines; D010047:Ovalbumin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine