A Brief Note
The degeneration and loss of striatal dopaminergic neurons in the brains of MPTP-treated marmosets—a model of Parkinson's disease—can be observed with exceptional clarity through various brain imaging analyses. The extent of this neuronal degeneration shows a strong correlation with the severity of a behavioral Parkinsonian sign.
Contents of this page
Figure 1. The marmoset brain is naturally smaller than that of macaques such as cynomolgus monkeys. However, when considering the ratio of the brain to the body weight of each, the marmoset brain is relatively extremely large compared to that of macaques (photo taken in the authors' laboratory).
Reference in Japanese:
Kiyoshi Ando (2008) Pathological model using marmosets: Parkinson's disease model, Marmoset MR brain atlas (edited by Hideyuki Okano/Tatsuji Nomura).
安東潔 (2008) マーモセットを用いた病態モデル:パーキンソン病モデル, マーモセット MR脳アトラス (岡野栄之/野村達次 監修)。
Figure 2. The brain of a marmoset is obviously larger than that of a rat. Considering that the body weight of a marmoset is about the same as that of a large adult rat, the brain of a marmoset is also relatively large. The figure shows a horizontal section of the brain, with the top view of the brain and the bottom view of the brain. Mastomys (Mastomys Natalensis) is a rodent that lives in West Africa and was used in research on infections such as Lassa fever (brain sample collection and photography: Shin Tanaka and Ryoichi Saito).
Reference in Japanese:
Kiyoshi Ando (2008) Pathological model using marmosets: Parkinson's disease model, Marmoset MR brain atlas (edited by Hideyuki Okano/Tatsuji Nomura).
Parkinson's disease model marmoset brain:
Created by subcutaneous administration of the neurotoxin MPTP
(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
See Parkinson's Model of Marmoset
Both of the brain images below are coronal sections showing
the caudate nucleus and putamen in the striatum.
Figure 3. In the tyrosine hydroxylase (TH) immunostaining of a normal brain shown on the left, staining was observed in the caudate nucleus and putamen of the striatum, indicating the distribution of dopamine (catecholamine) nerves. On the other hand, in the MPTP-treated marmoset brain shown on the right, there was almost no staining in the striatum, indicating degeneration and loss of the nerves. The coronal brain slice shows the area where staining is clearly observed in the striatum in a normal brain (image of brain specimen created by Kenji Kawai).
Reference:
Ando K, Inoue T, Hikishima K, Komaki Y, Kawai K, Inoue R, Nishime C, Nishinaka E, Urano K, Okano H (2020) Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious preclinical evaluations. Behav Pharmacol 31:45-60.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964884/pdf/bpharm-31-45.pdf
Figure 4. In the normal brain shown on the left, the dopamine neurotransporter ligand [11C]PE2I binding clearly shows the distribution of dopamine neurons in the striatum (caudate nucleus and putamen). In the MPTP-treated marmoset brain shown on the right, less ligand binding was observed in the striatum, indicating degeneration and loss of dopamine neurons (image of brain specimen prepared by Jun Maeda).
References:
Ando K, Maeda J, Inaji M, Okauchi T, Obayashi S, Higuchi M, Suhara T, Tanioka Y (2008) Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmosets. Psychopharmacology 195:509-516.
https://researchmap.jp/read0179769/published_papers/3505333
Reference in Japanese:
Kiyoshi Ando (2008) Pathological model using marmosets: Parkinson's disease model, Marmoset MR brain atlas (edited by Hideyuki Okano/Tatsuji Nomura).
安東潔 (2008) マーモセットを用いた病態モデル:パーキンソン病モデル, マーモセット MR脳アトラス (岡野栄之/野村達次 監修)。
(T2-weighted images)
Figure 5. No clear differences were observed between the normal marmoset brain (left) and the MPTP-treated marmoset brain (right) in the MRI T2 relaxation time weighted images taken at a magnetic field strength of 7T (MRI measurement/image creation: Masayuki Yamada).
No difference was also observed in the T2 relaxation time values themselves. However, an increase in the T1 relaxation time value was observed in the striatum of the MPTP-treated marmoset brain compared to the MPTP-free brain. Furthermore, in both MRI voxel base analysis and diffusion tensor analysis, changes suggesting degeneration and loss of dopamine neurons were observed in the MPTP-treated marmoset brain compared to the MPTP-free brain.
References:
Ando K, Inoue T, Hikishima K, Komaki Y, Kawai K, Inoue R, Nishime C, Nishinaka E, Urano K, Okano H (2020) Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious preclinical evaluations. Behav Pharmacol 31:45-60.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964884/pdf/bpharm-31-45.pdf
Hikishima K, Ando K, Komaki Y, Kawai K, Yano R, Inoue T, Ito T, Yamada M, Momoshima S, Okano SJ, Okano H (2015) Voxel-based morphometry of the marmoset brain: in vivo detection of volume loss in the substantia nigra of the MPTP-treated Parkinson's disease model. Neuroscience 300:585–592.
https://pubmed.ncbi.nlm.nih.gov/26012491/
Hikishima K, Ando K, Yano R, Kawai K, Komaki Y, Inoue T, Itoh T, Yamada M, Momoshima S, Okano JS, Okano H (2015) Parkinson disease: diffusion MR imaging to detect nigrostriatal pathway loss in a marmoset model treated with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine. Radiology 275:430–437.
(Specific binding potential of the ligand [11C] PE2I for dopamine transporter)
Figure 6. In the normal brain on the left, high specific binding of [11C] PE2I was observed in the striatum (caudate nucleus and putamen), capturing the distribution of dopamine neurons. In the MPTP-treated marmoset brain on the right, a significant decrease in the binding was observed, indicating degeneration and loss of dopamine neurons (PET measurement/analysis/image creation: Shigeru Obayashi and Yuji Nagai).
Reference:
Ando K, Obayashi S, Nagai Y, Oh-Nishi A, Minamimoto T, Higuchi M, et al. PET analysis of dopaminergic neurodegeneration in relation to immobility in the MPTP-treated common marmoset, a model for Parkinson's disease. PLoS One. 2012;7:e46371.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046371
Figure 7. Marmosets administered MPTP subcutaneously exhibit akinesia, one of the main symptoms of Parkinson's disease. This can be objectively and quantitatively measured as a decrease in locomotion by continuously measuring the locomotion or spontaneous motor activity of marmosets in individual cages over a long period of time. This index value and the specific binding ability of [11C]PE2I measured by PET in the marmoset brain showed a high correlation (r=0.97) in the striatum, especially in the putamen, as shown in the left figure. In addition, in the TH immunostaining of postmortem brains shown in the right figure, the decrease in locomotion during life was also highly correlated with the decrease in the immunostained area of the entire striatum. The immunostained area was quantified using NIH Image J. This shows that there is a clear correlation between the results of in vivo and in vitro measurements of the brain and behavior.
References:
Ando K, Obayashi S, Nagai Y, Oh-Nishi A, Minamimoto T, Higuchi M, et al. PET analysis of dopaminergic neurodegeneration in relation to immobility in the MPTP-treated common marmoset, a model for Parkinson's disease. PLoS One. 2012;7:e46371.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046371
Ando K, Inoue T, Hikishima K, Komaki Y, Kawai K, Inoue R, Nishime C, Nishinaka E, Urano K, Okano H (2020) Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious preclinical evaluations. Behav Pharmacol 31:45-60.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964884/pdf/bpharm-31-45.pdf
Reference in Japanese:
Ando K (1918) A common marmoset model of Parkinson's disease induced by administration of the neurotoxin MPTP – Preclinical evaluation using behavioral analysis – Obelisk Vol.23,1:14-22.
安東潔 (1918) 神経毒MPTP 投与によるコモンマーモセットのパーキンソン病モデル – 行動解析による前臨床評価を中心として – オベリスク Vol.23,1:14-22. https://researchmap.jp/read0179769/published_papers/19447809