Aβ1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation

Anni D, Weiss EM, Guhathakurta D, Akdas EY, Klueva J, Zeitler S, Andres-Alonso M, Huth T, Fejtová A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cellular and Molecular Life Sciences Springer

DOI: 10.1007/s00018-021-03835-5

Abstract

Amyloid beta (Aβ) is linked to the pathology of Alzheimer’s disease (AD). At physiological concentrations, Aβ was proposed to enhance neuroplasticity and memory formation by increasing the neurotransmitter release from presynapse. However, the exact mechanisms underlying this presynaptic effect as well as specific contribution of endogenously occurring Aβ isoforms remain unclear. Here, we demonstrate that Aβ1-42 and Aβ1-16, but not Aβ17-42, increased size of the recycling pool of synaptic vesicles (SV). This presynaptic effect was driven by enhancement of endogenous cholinergic signalling via α7 nicotinic acetylcholine receptors, which led to activation of calcineurin, dephosphorylation of synapsin 1 and consequently resulted in reorganization of functional pools of SV increasing their availability for sustained neurotransmission. Our results identify synapsin 1 as a molecular target of Aβ and reveal an effect of physiological concentrations of Aβ on cholinergic modulation of glutamatergic neurotransmission. These findings provide new mechanistic insights in cholinergic dysfunction observed in AD.

Authors with CRIS profile

Daniela Anni Department of Psychiatry and Psychotherapy Debarpan Guhathakurta Department of Psychiatry and Psychotherapy Enes Yagiz Akdas Department of Psychiatry and Psychotherapy Stefanie Zeitler Professur für Molekulare und Klinische Pharmazie Tobias Huth Lehrstuhl für Physiologie Anna Fejtová Professur für Molekulare Psychiatrie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

IZKF-J74 (PS): The role of CtBP1 in hippocampal and cortical neuroplasticity Feb. 1, 2019 - July 31, 2021

Involved external institutions

Max-Planck-Institut für Neurobiologie / Max Planck Institute of Neurobiology DE Germany (DE)

How to cite

APA:

Anni, D., Weiss, E.-M., Guhathakurta, D., Akdas, E.Y., Klueva, J., Zeitler, S.,... Fejtová, A. (2021). Aβ1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation. Cellular and Molecular Life Sciences. https://dx.doi.org/10.1007/s00018-021-03835-5

MLA:

Anni, Daniela, et al. "Aβ1-16 controls synaptic vesicle pools at excitatory synapses via cholinergic modulation of synapsin phosphorylation." Cellular and Molecular Life Sciences (2021).

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