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

Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9435-40. doi: 10.1073/pnas.0400569101. Epub 2004 Jun 14.

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.

Publication types

  • 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.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Adoptive Transfer*
  • Animals
  • Coat Protein Complex I / immunology*
  • Corpus Striatum / immunology
  • Corpus Striatum / pathology
  • Cytokines / analysis
  • Disease Models, Animal
  • Dopamine / immunology*
  • Immunohistochemistry
  • Mesencephalon / immunology*
  • Mesencephalon / pathology
  • Mice
  • Mycobacterium tuberculosis / immunology
  • Neurons / immunology*
  • Neurons / pathology
  • Ovalbumin / immunology
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / immunology*
  • Parkinsonian Disorders / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Substantia Nigra / immunology
  • Substantia Nigra / pathology
  • Transcription, Genetic

Substances

  • Coat Protein Complex I
  • Cytokines
  • Ovalbumin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine