Progression of phosphorylated α‐synuclein in Macaca fuscata
| Autor: | Mina Takase, Kazuyuki Samejima, Atsuko Motoda, Aki Shimozawa, Masami Masuda-Suzukake, Reiko Ohtani, Masato Hasegawa, Mari Kumashiro, Masashi Hashimoto, Ito Kawakami |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Synucleinopathies Neurite animal diseases Hippocampus Biology Amygdala Macaca fuscata Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine propagation medicine Animals heterocyclic compounds Letter to the Editor Inclusion Bodies Temporal cortex α‐synuclein Dementia with Lewy bodies animal model General Neuroscience Neurodegeneration Putamen Brain Parkinson Disease medicine.disease nervous system diseases Substantia Nigra 030104 developmental biology medicine.anatomical_structure nervous system Gliosis alpha-Synuclein health occupations Immunohistochemistry Lewy Bodies pathology progression Neurology (clinical) medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Brain Pathology |
| ISSN: | 1750-3639 1015-6305 |
| DOI: | 10.1111/bpa.12952 |
| Popis: | Prion‐like spreading of abnormal proteins is proposed to occur in neurodegenerative diseases, and the progression of α‐synuclein (α‐syn) deposits has been reported in the brains of animal models injected with synthetic α‐syn fibrils or pathological α‐syn prepared from patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, α‐syn transmission in nonhuman primates, which are more similar to humans, has not been fully clarified. Here, we injected synthetic human α‐syn fibrils into the left striatum of a macaque monkey (Macaca fuscata). At 3 months after the injection, we examined neurodegeneration and α‐syn pathology in the brain using α‐syn epitope‐specific antibodies, antiphosphorylated α‐syn antibodies (pSyn#64 and pSer129), anti‐ubiquitin antibodies, and anti‐p62 antibodies. Immunohistochemical examination with pSyn#64, pSer129, and α‐syn epitope‐specific antibodies revealed Lewy bodies, massive α‐syn‐positive neuronal intracytoplasmic inclusions (NCIs), and neurites in the left putamen. These inclusions were also positive for ubiquitin and p62. LB509, a human‐specific α‐syn antibody targeting amino acid residues 115–122, showed limited immunoreactivity around the injection site. The left substantia nigra (SN) and the bilateral frontal cortex also contained some NCIs and neurites. The left hemisphere, including parietal/temporal cortex presented sparse α‐syn pathology, and no immunoreactivity was seen in olfactory nerves, amygdala, hippocampus, or right parietal/temporal cortex. Neuronal loss and gliosis in regions with α‐syn pathology were mild, except for the left striatum and SN. Our results indicate that abnormal α‐syn fibrils propagate throughout the brain of M. fuscata via projection, association, and commissural fibers, though the progression of α‐syn pathology is limited. We investigated the pathological consequences of intracerebral injection of synthetic human α‐syn fibrils in Macaca fuscata. Immunohistochemical examination with α‐syn epitope‐specific antibodies revealed α‐syn‐positive neuronal intracytoplasmic inclusions and neurites in the injection site and related regions. Our results strongly indicate progression of α‐syn pathology via axonal connections through synaptically coupled networks. |
| Databáze: | OpenAIRE |
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