PloS one, 2015-10, Vol.10 (10), p.e0136575-e0136575
2015
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype
- Ist Teil von
- PloS one, 2015-10, Vol.10 (10), p.e0136575-e0136575
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with (oligodendro-)glial cytoplasmic α-synuclein (α-syn) inclusions (GCIs). Peripheral neuropathies have been reported in up to 40% of MSA patients, the cause remaining unclear. In a transgenic MSA mouse model featuring GCI-like inclusion pathology based on PLP-promoter driven overexpression of human α-syn in oligodendroglia motor and non-motor deficits are associated with MSA-like neurodegeneration. Since α-syn is also expressed in Schwann cells we aimed to investigate whether peripheral nerves are anatomically and functionally affected in the PLP-α-syn MSA mouse model. To this end, heat/cold as well as mechanical sensitivity tests were performed. Furthermore, in vivo and ex vivo nerve conduction and the G-ratios of the sciatic nerve were analyzed, and thermosensitive ion channel mRNA expression in dorsal root ganglia (DRG) was assessed. The presence of human α-syn in Schwann cells was associated with subtle behavioral impairments. The G-ratio of the sciatic nerve, the conduction velocity of myelinated and unmyelinated primary afferents and the expression of thermosensitive ion channels in the sensory neurons, however, were similar to wildtype mice. Our results suggest that the PNS appears to be affected by Schwann cell α-syn deposits in the PLP-α-syn MSA mouse model. However, there was no consistent evidence for functional PNS perturbations resulting from such α-syn aggregates suggesting a more central cause of the observed behavioral abnormalities. Nonetheless, our results do not exclude a causal role of α-syn in the pathogenesis of MSA associated peripheral neuropathy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0136575Titel-ID: cdi_plos_journals_1726401102
- Format
- –
- Schlagworte
- Abnormalities, Age, alpha-Synuclein - metabolism, Amyotrophic lateral sclerosis, Anatomy & physiology, Animals, Atrophy, Behavior, Behavior, Animal, Cold, Cold Temperature, Cytoplasm, Disease Models, Animal, Dorsal root ganglia, Embryology, Fluorescent Antibody Technique, Ganglia, Ganglia, Spinal - metabolism, Ganglia, Spinal - pathology, Gene expression, Gene Expression Regulation, Health physics, Histology, Hot Temperature, Human behavior, Humans, In vivo methods and tests, Inclusion bodies, Ion channels, Laboratory animals, Male, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Multiple System Atrophy - pathology, Multiple System Atrophy - physiopathology, Myelin proteolipid protein, Myelin Proteolipid Protein - genetics, Nerve conduction, Nervous system, Neural Conduction, Neurodegeneration, Neurology, Neuronal-glial interactions, Oligodendrocytes, Pain, Parkinson's disease, Pathogenesis, Pathology, Peripheral nerves, Peripheral neuropathy, Phenotype, Phenotypes, Physiology, RNA, Messenger - genetics, RNA, Messenger - metabolism, Schwann cells, Schwann Cells - metabolism, Sciatic nerve, Sciatic Nerve - pathology, Sensory neurons, Synuclein, Time Factors, Transient Receptor Potential Channels - genetics, Transient Receptor Potential Channels - metabolism, TRPA1 Cation Channel, TRPM Cation Channels - genetics, TRPM Cation Channels - metabolism