PET analysis of dopaminergic neurodegeneration in relation to immobility in the MPTP-treated common marmoset, a model for Parkinson's disease.
BACKGROUND
Positron Emission Tomography (PET) measurement was applied to the brain of the common marmoset, a small primate species, treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The marmoset shows prominent Parkinson's disease (PD) signs due to dopaminergic neural degeneration. Recently, the transgenic marmoset (TG) carrying human PD genes is developing. For phenotypic evaluations of TG, non-invasive PET measurement is considered to be substantially significant. As a reference control for TG, the brain of the MPTP-marmoset as an established and valid model was scanned by PET. Behavioral analysis was also performed by recording locomotion of the MPTP-marmoset, as an objective measure of PD signs.


RESULTS
MARMOSETS RECEIVED SEVERAL MPTP REGIMENS (SINGLE MPTP REGIMEN: 2 mg/kg, s.c., per day for 3 consecutive days) were used for PET measurement and behavioral observation. To measure immobility as a central PD sign, locomotion of marmosets in their individual living cages were recorded daily by infrared sensors. Daily locomotion counts decreased drastically after MPTP regimens and remained diminished for several months or more. PET scan of the brain, using [(11)C]PE2I as a ligand of the dopamine (DA) transporter, was performed once several months after the last MPTP regimen. The mean binding potential (BP(ND)) in the striatum (putamen and caudate) of the MPTP-marmoset group was significantly lower than that of the MPTP-free control group (n=5 for each group). In the MPTP-marmosets, the decrease of BP(ND) in the striatum closely correlated with the decrease in locomotion counts (r=0.98 in putamen and 0.91 in caudate).


CONCLUSIONS
The present characterization of neural degeneration using non-invasive PET imaging and of behavioral manifestation in the MPTP marmoset mimics typical PD characteristics and can be useful in evaluating the phenotype of TG marmosets being developed.
Central Institute for Experimental Animals, Kawasakiku, Kawasaki, Kanagawa, Japan. ando@ciea.or.jp
Kiyoshi
K
Ando
Shigeru
S
Obayashi
Yuji
Y
Nagai
Arata
A
Oh-Nishi
Takafumi
T
Minamimoto
Makoto
M
Higuchi
Takashi
T
Inoue
Toshio
T
Itoh
Tetsuya
T
Suhara
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D002144:Callithrix; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008124:Locomotion; D008297:Male; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D049268:Positron-Emission Tomography
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine