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ALTERED PHOSPHORYLATION OF MAP KINASE AFTER ACUTE EXPOSURE TO PCB153.
Citation:
Anderson, W. A., W R. Mundy, AND M. E. Gilbert. ALTERED PHOSPHORYLATION OF MAP KINASE AFTER ACUTE EXPOSURE TO PCB153. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2002.
Description:
Long-term potentiation (LTP) is a model of synaptic plasticity believed to encompass the physiological substrate of memory. The mitogen-activated protein kinase (ERK1/2) signalling cascade contributes to synaptic plasticity and to long-term memory formation. Learning and LTP stimulate calcium signalling pathways leading to a rapid phosphorylation and nuclear translocation of ERK1/2. The present series of experiments seeks to identify LTP-associated neurochemical signalling pathways that may be perturbed by exposure to PCBs. Hippocampal slices were prepared from naive animals and incubated for 1 hr in ACSF containing 0.1-30 mM PCB153 and 0.2% DMSO. Depolarization induced by a 10 min application of 50mM KCl results in a long-lasting synaptic potentiation emulating electrically-induced LTP. Slices were removed after KCl incubation, homogenized and prepared for gel electrophoresis. Western blot analysis was performed with antibodies recognizing total or phosphorylated ERK1/2. PCB153 produced no effect on ERK1/2 activity under nonstimulated (no KCl) conditions. Addition of KCl induced a 3-4 fold increase in phosphorylated ERK1/2 under control (DMSO) conditions. PCB153 induced a biphasic dose response relationship on KCl stimulation of ERK1/2 phosphorylation. Lower concentrations (0.1-3.0 mM) inhibited phospho-ERK1/2 formation, an effect that was reversed at concentrations of 10 and 30 mM. These data suggest that PCB153 may have a specific effect on ERK1/2 phosphorylation at low concentrations and indicate that acute exposure to PCB153 is sufficient to interfere with signalling molecules essential for synaptic plasticity. This abstract does not necessarily reflect US EPA policy.