Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic immunization efficacy in an animal model of Parkinson's disease.
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.
Boska
Michael D
MD
Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA.
Lewis
Travis B
TB
Destache
Christopher J
CJ
Benner
Eric J
EJ
Nelson
Jay A
JA
Uberti
Mariano
M
Mosley
R Lee
RL
Gendelman
Howard E
HE
D019264:Adoptive Transfer; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D004298:Dopamine / Q000502:physiology; D000068717:Glatiramer Acetate; D007114:Immunization; D020267:MPTP Poisoning / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D017628:Microglia / Q000502:physiology; D004676:Myelin Basic Protein / Q000276:immunology; D009410:Nerve Degeneration / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000032:analysis; D010047:Ovalbumin / Q000276:immunology; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000276:immunology*; D013378:Substantia Nigra / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D010455:Peptides; D001224:Aspartic Acid; D000068717:Glatiramer Acetate; D010047:Ovalbumin; C000179:N-acetylaspartate; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
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