Journal Article

DZNE-2020-05725

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Physiological Concentrations of Amyloid Beta Regulate Recycling of Synaptic Vesicles via Alpha7 Acetylcholine Receptor and CDK5/Calcineurin Signaling.

Lazarevic, V. (First author)DZNE* ; Fieńko, S. ; Andres-Alonso, M. ; Anni, D. ; Ivanova, D. ; Montenegro-Venegas, C. ; Gundelfinger, E. D.DZNE* ; Cousin, M. A. ; Fejtova, A. (Corresponding author)

2017
Frontiers Research Foundation Lausanne

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Please use a persistent id in citations: doi:10.3389/fnmol.2017.00221

Abstract: Despite the central role of amyloid β (Aβ) peptide in the etiopathogenesis of Alzheimer's disease (AD), its physiological function in healthy brain is still debated. It is well established that elevated levels of Aβ induce synaptic depression and dismantling, connected with neurotoxicity and neuronal loss. Growing evidence suggests a positive regulatory effect of Aβ on synaptic function and cognition; however the exact cellular and molecular correlates are still unclear. In this work, we tested the effect of physiological concentrations of Aβ species of endogenous origin on neurotransmitter release in rat cortical and hippocampal neurons grown in dissociated cultures. Modulation of production and degradation of the endogenous Aβ species as well as applications of the synthetic rodent Aβ40 and Aβ42 affected efficacy of neurotransmitter release from individual presynapses. Low picomolar Aβ40 and Aβ42 increased, while Aβ depletion or application of low micromolar concentration decreased synaptic vesicle recycling, showing a hormetic effect of Aβ on neurotransmitter release. These Aβ-mediated modulations required functional alpha7 acetylcholine receptors as well as extracellular and intracellular calcium, involved regulation of CDK5 and calcineurin signaling and increased recycling of synaptic vesicles. These data indicate that Aβ regulates neurotransmitter release from presynapse and suggest that failure of the normal physiological function of Aβ in the fine-tuning of SV cycling could disrupt synaptic function and homeostasis, which would, eventually, lead to cognitive decline and neurodegeneration.

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Contributing Institute(s):

1. Pathophysiology of Dementia (AG Reymann)
2. U Preclinical Researchers T1 - Magdeburg (U Preclinical Researchers T1 - Magdeburg)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2017

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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