Alpha-synuclein-positive structures induced in leupeptin-infused rats
| Autor: | Makoto Seki, R. Nishii, S. Takauchi, Masatoshi Takeda, Kazuyuki Ohara, Masahiro Kokai, Takaya Nakajima, Seishi Maeda, Yoshio Morita, Akinori Takanaga, T. Tanaka |
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| Rok vydání: | 2003 |
| Předmět: |
Pathology
medicine.medical_specialty Leupeptins Immunoelectron microscopy Fornix Brain Synucleins Nerve Tissue Proteins Biology Cysteine Proteinase Inhibitors Hippocampus chemistry.chemical_compound Atrophy In vivo mental disorders medicine Animals Rats Wistar Molecular Biology Injections Intraventricular Neurons Dementia with Lewy bodies General Neuroscience Secretory Vesicles Leupeptin Colocalization Neurofibrillary tangle Human brain Infusion Pumps Implantable medicine.disease nervous system diseases Rats medicine.anatomical_structure nervous system chemistry alpha-Synuclein Neurology (clinical) Developmental Biology |
| Zdroj: | Brain research. 1040(1-2) |
| ISSN: | 0006-8993 |
| Popis: | Abnormal accumulation of alpha-synuclein is regarded as a key pathological step in a wide range of neurodegenerative processes, not only in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but also in multiple-system atrophy (MSA). Nevertheless, the mechanism of alpha-synuclein accumulation remains unclear. Leupeptin, a protease inhibitor, has been known to cause various neuropathological changes in vivo resembling those of aging or neurodegenerative processes in the human brain, including the accumulation of neuronal processes and neuronal cytoskeletal abnormalities leading to neurofibrillary tangle (NFT)-like formations. In the present study, we administered leupeptin into the rat ventricle and found that alpha-synuclein-positive structures appeared widely in the neuronal tissue, mainly in neuronal processes of the fimbria and alveus. Immunoelectron microscopic study revealed that alpha-synuclein immunoreactivity was located in the swollen axons of the fimbria and alveus, especially in the dilated presynaptic terminals. In addition colocalization of alpha-synuclein with ubiquitin was rarely observed in confocal laser-scan image. This is the first report of experimentally induced in vivo accumulation of alpha-synuclein in non-transgenic rodent brain injected with a well-characterized protease inhibitor by an infusion pump. The present finding suggests that the local accumulation of alpha-synuclein might be induced by the impaired metabolism of alpha-synuclein, which are likely related to lysosomal or ubiquitin-independent proteasomal systems. |
| Databáze: | OpenAIRE |
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