Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: The environmental neurotoxicant PCB 95 promotes synaptogenesis via ryanodine receptor-dependent miR132 upregulation.

Authors: Lesiak, Adam; Zhu, Mingyan; Chen, Hao; Appleyard, Suzanne M; Impey, Soren; Lein, Pamela J; Wayman, Gary A

Published In J Neurosci, (2014 Jan 15)

Abstract: Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) are widespread environmental contaminants linked to neuropsychological dysfunction in children. NDL PCBs increase spontaneous Ca(2+) oscillations in neurons by stabilizing ryanodine receptor (RyR) calcium release channels in the open configuration, which results in CREB-dependent dendritic outgrowth. In this study, we address the question of whether activation of CREB by NDL PCBs also triggers dendritic spine formation. Nanomolar concentrations of PCB 95, a NDL congener with potent RyR activity, significantly increased spine density and the frequency of miniature EPSCs in primary dissociated rat hippocampal cultures coincident with upregulation of miR132. Inhibition of RyR, CREB, or miR132 as well as expression of a mutant p250GAP cDNA construct that is not suppressed by miR132 blocked PCB 95 effects on spines and miniature EPSCs. PCB 95 also induced spine formation via RyR- and miR132-dependent mechanisms in hippocampal slice cultures. These data demonstrate a novel mechanism of PCB developmental neurotoxicity whereby RyR sensitization modulates spine formation and synaptogenesis via CREB-mediated miR132 upregulation, which in turn suppresses the translation of p250GAP, a negative regulator of synaptogenesis. In light of recent evidence implicating miR132 dysregulation in Rett syndrome and schizophrenia, these findings identify NDL PCBs as potential environmental risk factors for neurodevelopmental disorders.

PubMed ID: 24431430 Exiting the NIEHS site

MeSH Terms: Animals; Cells, Cultured; Coculture Techniques; Environmental Pollutants/toxicity*; Excitatory Postsynaptic Potentials/drug effects; Excitatory Postsynaptic Potentials/genetics; Excitatory Postsynaptic Potentials/physiology; Female; Hippocampus/drug effects; Hippocampus/metabolism; Hippocampus/physiology; Male; MicroRNAs/biosynthesis*; Neurogenesis/drug effects; Neurogenesis/physiology*; Organ Culture Techniques; Polychlorinated Biphenyls/toxicity*; Rats; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel/physiology*; Spine/drug effects; Spine/physiology; Synapses/drug effects; Synapses/physiology*

Back
to Top