Chiang, H-C., Iijima, K., Hakker, I., Zhong, Y. (June 2009) Distinctive roles of different {beta}-amyloid 42 aggregates in modulation of synaptic functions. FASEB J., 23 (6). pp. 1969-1977.
Abstract
To determine how endogenously secreted {beta}-amyloid 42 (A{beta}42) aggregates regulate synaptic functions, we examined effects of A{beta}42 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 A{beta}42 in neurons leads to a reduction of neurotransmitter release. However, expression of A{beta}42 in postsynaptic muscle cells enhanced neurotransmitter release. Both effects are neutralized by A{beta} antibody, suggesting a role for secreted A{beta}42 peptides. Application of exogenously prepared A{beta}42 oligomers leads to a reduction in synaptic responses, whereas mixed A{beta}42 aggregates with mainly fibrils elicit an opposite effect by increasing synaptic transmission. Further analysis of long-term depression (LTD) confirms differential effects of different A{beta}42 aggregates. Taken together, our data suggest that A{beta}42 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 A{beta}42 aggregates, leading to different modulation of synaptic functions.--Chiang, H.-C., Iijima, K., Hakker, I., Zhong, Y. Distinctive roles of different {beta}-amyloid 42 aggregates in modulation of synaptic functions.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Alzheimer's disease Drosophila neuromuscular junction endogenous |
| Subjects: | diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease organism description > animal > insect > Drosophila bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression |
| CSHL Authors: | |
| Communities: | CSHL labs > Zhong lab |
| Depositing User: | CSHL Librarian |
| Date: | 1 June 2009 |
| Date Deposited: | 29 Mar 2012 19:19 |
| Last Modified: | 13 Mar 2018 16:58 |
| PMCID: | PMC2698658 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/25593 |
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