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The Journal of Neuroscience, February 16, 2005, 25(7):1691-1700; doi:10.1523/JNEUROSCI.4364-04.2005

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Neurobiology of Disease
Quantitative ¹H Magnetic Resonance Spectroscopic Imaging Determines Therapeutic Immunization Efficacy in an Animal Model of Parkinson's Disease

Michael D. Boska,^1,2 Travis B. Lewis,¹ Christopher J. Destache,^1,4 Eric J. Benner,¹ Jay A. Nelson,^1,2 Mariano Uberti,^1,2 R. Lee Mosley,^1,3 * and Howard E. Gendelman^1,3 *

¹Center for Neurovirology and Neurodegenerative Disorders, Departments of ²Radiology and ³Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, and ⁴Department of Pharmacy Practice, College of Pharmacy, Creighton University Medical Center, Omaha, Nebraska 68131

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.

Key words: Parkinson's disease; murine model; ¹H MRSI; spectroscopic quantitation; immune therapy; copolymer-1

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Received Oct 20, 2004; revised December 23, 2004; accepted December 23, 2004.

This article has been cited by other articles:

				A. D. Reynolds, R. Banerjee, J. Liu, H. E. Gendelman, and R. L. Mosley Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease J. Leukoc. Biol., November 1, 2007; 82(5): 1083 - 1094. [Abstract] [Full Text] [PDF]

				C. F. Orr, D. B. Rowe, Y. Mizuno, H. Mori, and G. M. Halliday A possible role for humoral immunity in the pathogenesis of Parkinson's disease Brain, November 1, 2005; 128(11): 2665 - 2674. [Abstract] [Full Text] [PDF]

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