Neuronal overexpression ofDYRK1A/minibrainalters motor decline, neurodegeneration and synaptic plasticity inDrosophila

Abstract

Author summaryDown syndrome (DS) is caused by three copies of chromosome 21 instead of the usual two. It is characterised by cognitive and motor deficits, which worsen with age resulting in Alzheimer's disease (AD). Which genes on chromosome 21 cause these phenotypes is incompletely understood. Here we demonstrate that neuronal overexpression of minibrain, the Drosophila ortholog of the chromosome 21 gene DYRK1A, causes age-dependent degeneration of brain neurons, accelerates age-dependent decline in motor performance and shortens lifespan. It also modifies presynaptic structure, enhances spontaneous transmitter release and slows recovery from short-term depression of synaptic transmission at a model glutamatergic synapse. These findings give insight into the role of DYRK1A overexpression in aberrant aging and altered information processing in DS and AD.