Dataset Information
PCB-95 modulates the calcium-dependent signaling pathway responsible for activity-dependent dendritic growth.
Ontology highlight
ABSTRACT: Background
Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) promote dendritic growth in hippocampal neurons via ryanodine receptor (RyR)-dependent mechanisms; however, downstream signaling events that link enhanced RyR activity to dendritic growth are unknown. Activity-dependent dendritic growth, which is a critical determinant of neuronal connectivity in the developing brain, is mediated by calcium ion (Ca(2+))-dependent activation of Ca(2+)/calmodulin kinase-I (CaMKI), which triggers cAMP response element binding protein (CREB)-dependent Wnt2 transcription. RyRs regulate the spatiotemporal dynamics of intracellular Ca(2+) signals, but whether RyRs promote dendritic growth via modulation of this signaling pathway is not known.Objective
We tested the hypothesis that the CaMKI-CREB-Wnt2 signaling pathway couples NDL PCB-enhanced RyR activity to dendritic arborization.Methods and results
Ca(2+) imaging of dissociated cultures of primary rat hippocampal neurons indicated that PCB-95 (2,2',3,5'6-pentachlorobiphenyl; a potent RyR potentiator), enhanced synchronized Ca(2+) oscillations in somata and dendrites that were blocked by ryanodine. As determined by Western blotting and quantitative polymerase chain reaction, PCB-95 also activated CREB and up-regulated Wnt2. Blocking CaMKK, CaMKI?/?, MEK/ERK, CREB, or Wnt2 prevented PCB-95-induced dendritic growth. Antagonism of ?-aminobutyric acid (GABA) receptors with bicuculline (BIC) phenocopied the dendrite-promoting effects of PCB-95, and pharmacological antagonism or siRNA knockdown of RyR blocked BIC-induced dendritic growth in dissociated and slice cultures of hippocampal neurons.Conclusions
RyR activity contributes to dynamic remodeling of dendritic architecture in response to NDL PCBs via CaMKI-CREB-Wnt2 signaling in rats. Our findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling associated with autism.
SUBMITTER: Wayman GA
PROVIDER: S-EPMC3404671 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
Publications
PCB-95 modulates the calcium-dependent signaling pathway responsible for activity-dependent dendritic growth.
Environmental health perspectives 20120425 7
<h4>Background</h4>Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) promote dendritic growth in hippocampal neurons via ryanodine receptor (RyR)-dependent mechanisms; however, downstream signaling events that link enhanced RyR activity to dendritic growth are unknown. Activity-dependent dendritic growth, which is a critical determinant of neuronal connectivity in the developing brain, is mediated by calcium ion (Ca(2+))-dependent activation of Ca(2+)/calmodulin kinase-I (CaMKI), which trig ...[more]
