C-Abl Deficiency Provides Synaptic Resiliency Against A?-Oligomers.

ABSTRACT: Spine pathology has been implicated in the early onset of Alzheimer's disease (AD), where A?-Oligomers (A?Os) cause synaptic dysfunction and loss. Previously, we described that pharmacological inhibition of c-Abl prevents A?Os-induced synaptic alterations. Hence, this kinase seems to be a key element in AD progression. Here, we studied the role of c-Abl on dendritic spine morphological changes induced by A?Os using c-Abl null neurons (c-Abl-KO). First, we characterized the effect of c-Abl deficiency on dendritic spine density and found that its absence increases dendritic spine density. While A?Os-treatment reduces the spine number in both wild-type (WT) and c-Abl-KO neurons, A?Os-driven spine density loss was not affected by c-Abl. We then characterized A?Os-induced morphological changes in dendritic spines of c-Abl-KO neurons. A?Os induced a decrease in the number of mushroom spines in c-Abl-KO neurons while preserving the populations of immature stubby, thin, and filopodia spines. Furthermore, synaptic contacts evaluated by PSD95/Piccolo clustering and cell viability were preserved in A?Os-exposed c-Abl-KO neurons. In conclusion, our results indicate that in the presence of A?Os c-Abl participates in synaptic contact removal, increasing susceptibility to A?Os damage. Its deficiency increases the immature spine population reducing A?Os-induced synapse elimination. Therefore, c-Abl signaling could be a relevant actor in the early stages of AD.

SUBMITTER: Gutierrez DA 

PROVIDER: S-EPMC6902026 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature