Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss
Abstract α-Synuclein is a protein involved in the pathogenesis of synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We investigated the role of neuronal α-Syn in myelin composition and abnormalities. The phospholipid content of...
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| Format: | Article |
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BMC
2017-05-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | http://link.springer.com/article/10.1186/s40478-017-0439-3 |
| _version_ | 1828357435470905344 |
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| author | Jessica Grigoletto Katharina Pukaß Ayelet Gamliel Dana Davidi Rachel Katz-Brull Christiane Richter-Landsberg Ronit Sharon |
| author_facet | Jessica Grigoletto Katharina Pukaß Ayelet Gamliel Dana Davidi Rachel Katz-Brull Christiane Richter-Landsberg Ronit Sharon |
| author_sort | Jessica Grigoletto |
| collection | DOAJ |
| description | Abstract α-Synuclein is a protein involved in the pathogenesis of synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We investigated the role of neuronal α-Syn in myelin composition and abnormalities. The phospholipid content of purified myelin was determined by 31P NMR in two mouse lines modeling PD, PrP-A53T α-Syn and Thy-1 wt-α-Syn. Significantly higher levels of phospholipids were detected in myelin purified from brains of these α-Syn transgenic mouse models than in control mice. Nevertheless, myelin ultrastructure appeared intact. To further investigate the effect of α-Syn on myelin abnormalities, we systematically analyzed the striatum, a brain region associated with neurodegeneration in PD. An age and disease-dependent loss of myelin basic protein (MBP) signal was detected by immunohistochemistry in striatal striosomes (patches). The age-dependent loss of MBP signal was associated with lower P25α levels in oligodendrocytes. In addition, we found that α-Syn inhibited oligodendrocyte maturation and the formation of membranous sheets in vitro. Based on these results we concluded that neuronal α-Syn is involved in the regulation and/or maintenance of myelin phospholipid. However, axonal hypomyelination in the PD models is evident only in progressive stages of the disease and associated with α-Syn toxicity. |
| first_indexed | 2024-04-14T03:14:30Z |
| format | Article |
| id | doaj.art-26c37e2758474247b07cbe59234c5b99 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-14T03:14:30Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-26c37e2758474247b07cbe59234c5b992022-12-22T02:15:30ZengBMCActa Neuropathologica Communications2051-59602017-05-015111610.1186/s40478-017-0439-3Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin lossJessica Grigoletto0Katharina Pukaß1Ayelet Gamliel2Dana Davidi3Rachel Katz-Brull4Christiane Richter-Landsberg5Ronit Sharon6Biochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical SchoolDepartment of Neuroscience, Molecular Neurobiology, University of OldenburgDepartment of Radiology, Hadassah-Hebrew University Medical CenterBiochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical SchoolDepartment of Radiology, Hadassah-Hebrew University Medical CenterDepartment of Neuroscience, Molecular Neurobiology, University of OldenburgBiochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical SchoolAbstract α-Synuclein is a protein involved in the pathogenesis of synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We investigated the role of neuronal α-Syn in myelin composition and abnormalities. The phospholipid content of purified myelin was determined by 31P NMR in two mouse lines modeling PD, PrP-A53T α-Syn and Thy-1 wt-α-Syn. Significantly higher levels of phospholipids were detected in myelin purified from brains of these α-Syn transgenic mouse models than in control mice. Nevertheless, myelin ultrastructure appeared intact. To further investigate the effect of α-Syn on myelin abnormalities, we systematically analyzed the striatum, a brain region associated with neurodegeneration in PD. An age and disease-dependent loss of myelin basic protein (MBP) signal was detected by immunohistochemistry in striatal striosomes (patches). The age-dependent loss of MBP signal was associated with lower P25α levels in oligodendrocytes. In addition, we found that α-Syn inhibited oligodendrocyte maturation and the formation of membranous sheets in vitro. Based on these results we concluded that neuronal α-Syn is involved in the regulation and/or maintenance of myelin phospholipid. However, axonal hypomyelination in the PD models is evident only in progressive stages of the disease and associated with α-Syn toxicity.http://link.springer.com/article/10.1186/s40478-017-0439-3α-SynucleinMyelinPhospholipidsParkinson’s disease |
| spellingShingle | Jessica Grigoletto Katharina Pukaß Ayelet Gamliel Dana Davidi Rachel Katz-Brull Christiane Richter-Landsberg Ronit Sharon Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss Acta Neuropathologica Communications α-Synuclein Myelin Phospholipids Parkinson’s disease |
| title | Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss |
| title_full | Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss |
| title_fullStr | Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss |
| title_full_unstemmed | Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss |
| title_short | Higher levels of myelin phospholipids in brains of neuronal α-Synuclein transgenic mice precede myelin loss |
| title_sort | higher levels of myelin phospholipids in brains of neuronal α synuclein transgenic mice precede myelin loss |
| topic | α-Synuclein Myelin Phospholipids Parkinson’s disease |
| url | http://link.springer.com/article/10.1186/s40478-017-0439-3 |
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