| First Author | Ito H | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 428 |
| Issue | 3 | Pages | 348-53 |
| PubMed ID | 23098910 | Mgi Jnum | J:190679 |
| Mgi Id | MGI:5449463 | Doi | 10.1016/j.bbrc.2012.10.057 |
| Citation | Ito H, et al. (2012) alpha-Synuclein accumulation reduces GABAergic inhibitory transmission in a model of multiple system atrophy. Biochem Biophys Res Commun 428(3):348-53 |
| abstractText | Multiple system atrophy is a neurodegenerative disease caused by abnormal alpha-synuclein (alpha-syn) accumulation in oligodendrocytes and neurons. We previously demonstrated that transgenic (Tg) mice that selectively overexpressed human alpha-syn in oligodendrocytes exhibited neuronal alpha-syn accumulation. Microtubule beta-III tubulin binds to endogenous neuronal alpha-syn to form an insoluble complex, leading to progressive neuronal degeneration. alpha-Syn accumulation is increased in the presynaptic terminals of Tg mice neurons and may reduce neurotransmitter release. To clarify the mechanisms underlying its involvement in neuronal dysfunction, in the present study, we investigated the effects of neuronal alpha-syn accumulation on synaptic function in Tg mice. Using whole-cell patch-clamp recording, we found that the frequency of miniature inhibitory postsynaptic currents was reduced in Tg mice. Furthermore, a microtubule depolymerizing agent restored normal frequencies of miniature inhibitory postsynaptic currents in Tg mice. These findings suggest that alpha-syn and beta-III tubulin protein complex plays roles for regulation of synaptic vesicle release in GABAergic interneurons, and it causes to reduce GABAergic inhibitory transmission. |
