Distinctive roles of different β-amyloid 42 aggregates in modulation of synaptic functions

Hsueh Cheng Chiang, Koichi Iijima, Inessa Hakker, Yi Zhong

研究成果: Article同行評審

21 引文 斯高帕斯(Scopus)

摘要

To determine how endogenously secreted β-amyloid 42 (Aβ42) aggregates regulate synaptic functions, we examined effects of Aβ42 at the neuromuscular junction of Drosophila larvae. Voltage-clamp recordings of synaptic transmission and optical analysis of vesicle recycling at presynaptic terminals show that expression of Aβ42 in neurons leads to a reduction of neurotransmitter release. However, expression of Aβ42 in postsynaptic muscle cells enhanced neurotransmitter release. Both effects are neutralized by Aβ antibody, suggesting a role for secreted Aβ42 peptides. Application of exogenously prepared Aβ42 oligomers leads to a reduction in synaptic responses, whereas mixed Aβ42 aggregates with mainly fibrils elicit an opposite effect by increasing synaptic transmission. Further analysis of long-term depression (LTD) confirms differential effects of different Aβ42 aggregates. Taken together, our data suggest that Aβ42 is secreted from neurons primarily as oligomers that inhibit neurotransmitter release and exert no effect on LTD. Whereas larger-sized aggregates, possibly fibrils, are major components secreted from muscle cells, which enhance synaptic transmission and LTD. Thus, different types of cells may secrete distinct forms of Aβ42 aggregates, leading to different modulation of synaptic functions.

原文English
頁(從 - 到)1969-1977
頁數9
期刊FASEB Journal
23
發行號6
DOIs
出版狀態Published - 2009 6月

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 生物化學
  • 分子生物學
  • 遺傳學

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