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Activity-independent release of the amyloid β-peptide from rat brain nerve terminals.

Lundgren, Jolanta L; Ahmed, Saheeb; Winblad, Bengt; Gouras, Gunnar LU ; Tjernberg, Lars O and Frykman, Susanne (2014) In Neuroscience Letters 566(Mar 3). p.125-130
Abstract
Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease. The molecular mechanism underlying this degeneration is not fully elucidated but one key player appears to be the synaptotoxic amyloid β-peptide (Aβ). The exact localization of the production of Aβ and the mechanisms whereby Aβ is released remain elusive. We have earlier shown that Aβ can be produced in crude synaptic vesicle fractions and it has been reported that increased synaptic activity results in increased secreted but decreased intracellular Aβ levels. Therefore, we considered whether Aβ could be produced in synaptic vesicles and/or released through the same mechanisms as neurotransmitters in synaptic vesicle exocytosis. Small amounts of Aβ were found to... (More)
Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease. The molecular mechanism underlying this degeneration is not fully elucidated but one key player appears to be the synaptotoxic amyloid β-peptide (Aβ). The exact localization of the production of Aβ and the mechanisms whereby Aβ is released remain elusive. We have earlier shown that Aβ can be produced in crude synaptic vesicle fractions and it has been reported that increased synaptic activity results in increased secreted but decreased intracellular Aβ levels. Therefore, we considered whether Aβ could be produced in synaptic vesicles and/or released through the same mechanisms as neurotransmitters in synaptic vesicle exocytosis. Small amounts of Aβ were found to be produced in pure synaptic vesicle preparations. We also studied the release of glutamate and Aβ from rat cortical nerve terminals (synaptosomes). We found that large amounts of Aβ were secreted from non-stimulated synaptosomes, from which glutamate was not released. On the contrary, we could not detect any differences in Aβ release between non-stimulated synaptosomes and synaptosomes stimulated with KCl or 4-aminopyridine, whereas glutamate release was readily inducible in this system. To conclude, our results indicate that the major release mechanism of Aβ from isolated nerve terminals differs from the synaptic release of glutamate and that the activity-dependent increase of secreted Aβ, reported by several groups using intact cells, is likely dependent on post-synaptic events, trafficking and/or protein synthesis mechanisms. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neuroscience Letters
volume
566
issue
Mar 3
pages
125 - 130
publisher
Elsevier
external identifiers
  • pmid:24602978
  • wos:000335613800026
  • scopus:84896117270
ISSN
0304-3940
DOI
10.1016/j.neulet.2014.02.050
language
English
LU publication?
yes
id
40117308-3bdc-41f8-b66c-e38271b0ce09 (old id 4383781)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24602978?dopt=Abstract
date added to LUP
2014-04-02 19:42:29
date last changed
2017-02-05 03:15:53
@article{40117308-3bdc-41f8-b66c-e38271b0ce09,
  abstract     = {Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease. The molecular mechanism underlying this degeneration is not fully elucidated but one key player appears to be the synaptotoxic amyloid β-peptide (Aβ). The exact localization of the production of Aβ and the mechanisms whereby Aβ is released remain elusive. We have earlier shown that Aβ can be produced in crude synaptic vesicle fractions and it has been reported that increased synaptic activity results in increased secreted but decreased intracellular Aβ levels. Therefore, we considered whether Aβ could be produced in synaptic vesicles and/or released through the same mechanisms as neurotransmitters in synaptic vesicle exocytosis. Small amounts of Aβ were found to be produced in pure synaptic vesicle preparations. We also studied the release of glutamate and Aβ from rat cortical nerve terminals (synaptosomes). We found that large amounts of Aβ were secreted from non-stimulated synaptosomes, from which glutamate was not released. On the contrary, we could not detect any differences in Aβ release between non-stimulated synaptosomes and synaptosomes stimulated with KCl or 4-aminopyridine, whereas glutamate release was readily inducible in this system. To conclude, our results indicate that the major release mechanism of Aβ from isolated nerve terminals differs from the synaptic release of glutamate and that the activity-dependent increase of secreted Aβ, reported by several groups using intact cells, is likely dependent on post-synaptic events, trafficking and/or protein synthesis mechanisms.},
  author       = {Lundgren, Jolanta L and Ahmed, Saheeb and Winblad, Bengt and Gouras, Gunnar and Tjernberg, Lars O and Frykman, Susanne},
  issn         = {0304-3940},
  language     = {eng},
  number       = {Mar 3},
  pages        = {125--130},
  publisher    = {Elsevier},
  series       = {Neuroscience Letters},
  title        = {Activity-independent release of the amyloid β-peptide from rat brain nerve terminals.},
  url          = {http://dx.doi.org/10.1016/j.neulet.2014.02.050},
  volume       = {566},
  year         = {2014},
}