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PMID: 15197276 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 25 ·2004-06-22 ·Pages 9435-40

Benner EJ, Mosley RL, Destache CJ, Lewis TB, Jackson-Lewis V, Gorantla S, Nemachek C, Green SR, Przedborski S, Gendelman HE

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.

MeSH Terms
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Adoptive Transfer Animals Coat Protein Complex I/immunology Corpus Striatum/immunology,pathology Cytokines/analysis Disease Models, Animal Dopamine/immunology Immunohistochemistry Mesencephalon/immunology,pathology Mice Mycobacterium tuberculosis/immunology Neurons/immunology,pathology Ovalbumin/immunology Parkinsonian Disorders/chemically induced,immunology,pathology Reverse Transcriptase Polymerase Chain Reaction Substantia Nigra/immunology,pathology Transcription, Genetic
Chemicals
Coat Protein Complex I Cytokines Ovalbumin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Dopamine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Benner Eric J
Center for Neurovirology and Neurodegenerative Disorders and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198, USA.
Mosley R Lee
Destache Chris J
Lewis Travis B
Jackson-Lewis Vernice
Gorantla Santhi
Nemachek Craig
Green Steven R
Przedborski Serge
Gendelman Howard E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0400569101
Published
2004-06-22
Epub
2004-00-14
Pages
9435-40
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC438994
Subset
IM
Grants
NINDS NIH HHS · R01 NS38586 · United States
NIA NIH HHS · R01 AG021617 · United States
NINDS NIH HHS · P50 NS038370 · United States
NINDS NIH HHS · P50 NS 38370 · United States
NINDS NIH HHS · 1T32 NS07488 · United States
NIMH NIH HHS · P01 MH64570 · United States
NCRR NIH HHS · P20RR15635 · United States
NIMH NIH HHS · P01 MH064570 · United States
NINDS NIH HHS · R01 NS 42269 · United States
NINDS NIH HHS · R37 NS036126 · United States
NINDS NIH HHS · P01 NS011766 · United States
NINDS NIH HHS · T32 NS007488 · United States
NCRR NIH HHS · P20 RR015635 · United States
NINDS NIH HHS · R01 NS042269 · United States
NINDS NIH HHS · R01 NS038586 · United States
NINDS NIH HHS · 2R37 NS36126 · United States
NINDS NIH HHS · P01 NS11766 · United States
External Links
PubMed source DOI: 10.1073/pnas.0400569101 PMC Full Text View journal details
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