Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic immunization efficacy in an animal model of Parkinson's disease

Michael D. Boska, Travis B. Lewis, Christopher J. Destache, Eric J. Benner, Jay A. Nelson, Mariano Uberti, R. Lee Mosley, Howard E. Gendelman

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Nigrostriatal degeneration, the pathological hallmark of Parkinson's disease (PD), is mirrored by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. MPTP-treated animals show the common behavioral, motor, and pathological features of human disease. We demonstrated previously that adoptive transfer of Copaxone (Cop-1) immune cells protected the nigrostriatal dopaminergic pathway in MPTP-intoxicated mice. Herein, we evaluated this protection by quantitative proton magnetic resonance spectroscopic imaging (1H MRSI). 1H MRSI performed in MPTP-treated mice demonstrated that N-acetyl aspartate (NAA) was significantly diminished in the substantia nigra pars compacta (SNpc) and striatum, regions most affected in human disease. When the same regions were coregistered with immunohistochemical stains for tyrosine hydroxylase, numbers of neuronal bodies and termini were similarly diminished. MPTP-intoxicated animals that received Cop-1 immune cells showed NAA levels, in the SNpc and striatum, nearly equivalent to PBS-treated animals. Moreover, adoptive transfer of immune cells from ovalbumin-immunized to MPTP-treated mice failed to alter NAA levels or protect dopaminergic neurons and their projections. These results demonstrate that 1H MRSI can evaluate dopaminergic degeneration and its protection by Cop-1 immunization strategies. Most importantly, the results provide a monitoring system to assess therapeutic outcomes for PD.

Original languageEnglish (US)
Pages (from-to)1691-1700
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number7
DOIs
StatePublished - Feb 16 2005

Keywords

  • Copolymer-1
  • H MRSI
  • Immune therapy
  • Murine model
  • Parkinson's disease
  • Spectroscopic quantitation

ASJC Scopus subject areas

  • Neuroscience(all)

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