Physiological Concentrations of Amyloid Beta Regulate Recycling of Synaptic Vesicles via Alpha7 Acetylcholine Receptor and CDK5/Calcineurin Signaling

Lazarevic V, Fienko S, Andres-Alonso M, Anni D, Ivanova D, Montenegro-Venegas C, Gundelfinger ED, Cousin MA, Fejtova A (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Frontiers in Molecular Neuroscience Frontiers Research Foundation / Frontiers Media

Book Volume: 10

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 Aβ40and Aβ42affected efficacy of neurotransmitter release from individual presynapses. Low picomolar Aβ40and Aβ42increased, 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.

Authors with CRIS profile

Daniela Anni Department of Psychiatry and Psychotherapy

Involved external institutions

Max-Planck-Institut für Neurobiologie / Max Planck Institute of Neurobiology DE Germany (DE) University of Edinburgh GB United Kingdom (GB)

How to cite

APA:

Lazarevic, V., Fienko, S., Andres-Alonso, M., Anni, D., Ivanova, D., Montenegro-Venegas, C.,... Fejtova, A. (2017). Physiological Concentrations of Amyloid Beta Regulate Recycling of Synaptic Vesicles via Alpha7 Acetylcholine Receptor and CDK5/Calcineurin Signaling. Frontiers in Molecular Neuroscience, 10. https://dx.doi.org/10.3389/fnmol.2017.00221

MLA:

Lazarevic, Vesna, et al. "Physiological Concentrations of Amyloid Beta Regulate Recycling of Synaptic Vesicles via Alpha7 Acetylcholine Receptor and CDK5/Calcineurin Signaling." Frontiers in Molecular Neuroscience 10 (2017).

BibTeX: Download