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

Autor: Lundgren JL; Karolinska Institutet, Department of Neurobiology, Care Science and Society, Center for Alzheimer Research, Novum level 5, 141 86 Stockholm, Sweden., Ahmed S; European Neuroscience Institute, Grisebachstrasse 5, 37077 Göttingen, Germany., Winblad B; Karolinska Institutet, Department of Neurobiology, Care Science and Society, Center for Alzheimer Research, Novum level 5, 141 86 Stockholm, Sweden., Gouras GK; Lund University, Department of Experimental Medical Science, Experimental Dementia Research Unit, Sölveg 19, BMC B12, 221 84 Lund, Sweden., Tjernberg LO; Karolinska Institutet, Department of Neurobiology, Care Science and Society, Center for Alzheimer Research, Novum level 5, 141 86 Stockholm, Sweden., Frykman S; Karolinska Institutet, Department of Neurobiology, Care Science and Society, Center for Alzheimer Research, Novum level 5, 141 86 Stockholm, Sweden. Electronic address: susanne.frykman@ki.se.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2014 Apr 30; Vol. 566, pp. 125-30. Date of Electronic Publication: 2014 Mar 03.
DOI: 10.1016/j.neulet.2014.02.050
Abstrakt: 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.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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