Mapping of Rat Brain Using the Synuclein-1 Monoclonal Antibody Reveals Somatodendritic Expression of α-Synuclein in Populations of Neurons Homologous to those Vulnerable to Lewy Body Formation in Human Synucleopathies
| Autor: | Thomas N. Chase, Gerda Andringa, Fu Du, M. Catherine Bennett |
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| Rok vydání: | 2003 |
| Předmět: |
Male
animal diseases Blotting Western Synucleins Enzyme-Linked Immunosorbent Assay Nerve Tissue Proteins Substantia nigra Biology Pathology and Forensic Medicine Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound medicine Animals Humans Tissue Distribution Axon Neurons Alpha-synuclein Lewy body Neurodegeneration Antibodies Monoclonal Brain Dendrites General Medicine Middle Aged medicine.disease Immunohistochemistry Rats nervous system diseases medicine.anatomical_structure nervous system Neurology chemistry alpha-Synuclein Synuclein Lewy Bodies Neurology (clinical) Neuron Neuroscience |
| Zdroj: | Journal of Neuropathology & Experimental Neurology. 62:1060-1075 |
| ISSN: | 1554-6578 0022-3069 |
| Popis: | The neuronal protein alpha-synuclein has been implicated in the pathogenesis of Parkinson disease and other neurodegenerative diseases. Although many studies report that alpha-synuclein expression is restricted to neuronal presynaptic terminals, this protein aggregates in Lewy bodies in somata that are typically distant from their axon terminals. Few studies have addressed this paradox and there has been no compelling explanation proposed for the apparent discrepancy between the locus of neuronal alpha-synuclein expression and the loci of Lewy bodies in the majority of Parkinson disease cases. We explored this issue by extensively characterizing the monoclonal antibody Synuclein-1 (Syn-1) and using this highly selective antibody to map the distribution of alpha-synuclein throughout rat brain and in human substantia nigra (SN). Additionally, alpha-synuclein expression in rat SN detected by 2 polyclonal antibodies against alpha-synuclein was compared with that detected by the Syn-1 antibody. In contrast with many previous reports, alpha-synuclein was detected by Syn-1 in neuronal somata and dendrites in restricted brain regions, as well as more ubiquitously in axons and terminals. The strongest alpha-synuclein neuronal expression in rat was found in brainstem and cortical regions that are homologous to regions prone to Lewy body formation in humans. The Syn-1 antibody labeled abundant somatodendritic alpha-synuclein in both rat and human SN, a major locus of Lewy body formation and neurodegeneration in Parkinson disease. By contrast, very few immunoreactive somata in the rat SN were labeled by the 2 polyclonal antibodies. We explore possible explanations for the differences in conflicting reports of patterns of alpha-synuclein expression in brain, including differences among antibodies. |
| Databáze: | OpenAIRE |
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