Characterization and reversal of Doxorubicin-mediated biphasic activation of ERK and persistent excitability in sensory neurons of Aplysia californica.

ABSTRACT: Doxorubicin (DOX), a common chemotherapeutic agent, impairs synaptic plasticity. DOX also causes a persistent increase in basal neuronal excitability, which occludes serotonin-induced enhanced excitability. Therefore, we sought to characterize and reverse DOX-induced physiological changes and modulation of molecules implicated in memory induction using sensory neurons from the marine mollusk Aplysia californica. DOX produced two mechanistically distinct phases of extracellular signal-regulated kinase (ERK) activation, an early and a late phase. Inhibition of MEK (mitogen-activated protein kinase (MAPK)/ERK kinase) after DOX treatment reversed the late ERK activation. MEK inhibition during treatment enhanced the late ERK activation possibly through prolonged downregulation of MAPK phosphata

SUBMITTER: Lakshminarasimhan H 

PROVIDER: S-EPMC5495788 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature