Proton magnetic resonance imaging and spectroscopy identify metabolic changes in the striatum in the MPTP feline model of parkinsonism.
We administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to adult, male cats to model Parkinson's disease (PD), and utilized proton magnetic resonance imaging (MRI) and spectroscopy (MRS) at a field strength of 1.5 T to identify metabolic degenerative changes in the striatum in vivo. Neurologic status and somatosensory-evoked potentials in vivo, as well as postmortem striatal histopathological and immunohistochemical parameters, were examined. Nine cats were equally divided into three groups and treated daily for 10 days as follows: saline, MPTP, and pargyline (a monoamine oxidase inhibitor) plus MPTP. The MPTP-treated cats displayed bradykinesia, head tremor, and reduced oculovestibular reflex activity. MRI showed a diffuse increase of the T2-weighted signal in the striatum of two MPTP-treated cats. Analysis of the MRS spectra indicated significantly lower N-acetylaspartate/creatine (CR) and glutamine-glutamate complex/CR ratios than the control baseline. Two MPTP-treated cats had low choline-containing compounds/CR ratio, whereas a lactate peak was present in all MPTP-treated cats. In the striatum of the MPTP-treated cats, there was a significant decline of tyrosine hydroxylase immunoreactivity and histological evidence for a diffuse cytotoxic reaction. Pretreatment with pargyline attenuated the MPTP-induced clinical signs, MRI and MRS changes, and the histopathological and immunoreactivity alterations. We conclude that proton MRI/MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alteration of the striatum in a feline model of PD.
Podell
Michael
M
Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH 43210, USA.
Hadjiconstantinou
Maria
M
Smith
Mark A
MA
Neff
Norton H
NH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002415:Cats; D002794:Choline / Q000032:analysis / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003401:Creatine / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D007294:Inositol / Q000032:analysis / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009460:Neurologic Examination; D010293:Pargyline / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism*; D011237:Predictive Value of Tests; D011522:Protons; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D011522:Protons; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D003401:Creatine; D002794:Choline