Abstract
BackgroundPositron 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.Methodology/Principal FindingsMarmosets 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 [11C]PE2I as a ligand of the dopamine (DA) transporter, was performed once several months after the last MPTP regimen. The mean binding potential (BPND) 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 BPND in the striatum closely correlated with the decrease in locomotion counts (r = 0.98 in putamen and 0.91 in caudate).Conclusion/SignificanceThe 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.
Highlights
Parkinson’s disease (PD) is a movement disorder caused by degeneration of nigrostriatal dopamine (DA) neurons in the brain and is thought to have several contributing factors, including genetic predisposition and environmental toxins [1]
CLEA Japan, Inc. (Tokyo, Japan), were used in this study. These marmosets received subcutaneous (s.c.) administration of MPTP, and the behavioral consequences were observed at the Central Institute for Experimental Animals (CIEA) the animals were sent to the National Institute of Radiological Sciences (NIRS) for Positron Emission Tomography (PET) scanning and analysis
The actual locomotion count varied among marmosets, the daily locomotion count was stable for each individual marmoset during the 7-day period
Summary
Parkinson’s disease (PD) is a movement disorder caused by degeneration of nigrostriatal dopamine (DA) neurons in the brain and is thought to have several contributing factors, including genetic predisposition and environmental toxins [1]. Recent findings indicate that the underlying mechanisms of cell degeneration and death are based on oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, and apoptosis [2]. Intracellular proteinaceous inclusions such as Lewy bodies, which are composed mainly of alpha-synuclein, are common neural features of PD [3,4]. MPTP-treated primates exhibit the neural damage and signs of PD such as moving tremors, immobility, muscle rigidity, and positional dysfunction that are observed in humans [8,9,10,11]. 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). Behavioral analysis was performed by recording locomotion of the MPTP-marmoset, as an objective measure of PD signs
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