Genetic removal of synaptic Zn²⁺ impairs cognition, alters neurotrophic signaling and induces neuronal hyperactivity.

ABSTRACT: Vesicular Zn²⁺ (zinc) is released at synapses and has been demonstrated to modulate neuronal responses. However, mechanisms through which dysregulation of zinc homeostasis may potentiate neuronal dysfunction and neurodegeneration are not well-understood. We previously reported that accumulation of soluble amyloid beta oligomers (AβO) at synapses correlates with synaptic loss and that AβO localization at synapses is regulated by synaptic activity and enhanced by the release of vesicular Zn²⁺ in the hippocampus, a brain region that deteriorates early in Alzheimer's disease (AD). Significantly, drugs regulating zinc homeostasis inhibit AβO accumulation and improve cognition in mouse models of AD. We used both sexes of a transgenic mouse model lacking synaptic Zn^2+</

SUBMITTER: Vogler EC 

PROVIDER: S-EPMC9895830 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature