PCB-95 Promotes Dendritic Growth via Ryanodine Receptor-Dependent Mechanisms

Background: Aroclor 1254 (A1254) interferes with normal dendritic growth and plasticity in the developing rodent brain, but the mechanism(s) mediating this effect have yet to be established. Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) enhance the activity of ryanodine receptor (RyR) calci...

Full description

Saved in:
Bibliographic Details
Published in:Environmental health perspectives 2012-07, Vol.120 (7), p.997-1002
Main Authors: Wayman, Gary A., Yang, Dongren, Bose, Diptiman D., Lesiak, Adam, Ledoux, Veronica, Bruun, Donald, Pessah, Isaac N., Lein, Pamela J.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain
Calcium
Cells, Cultured
Congeners
Dendrites - drug effects
Dendritic cells
Environment. Living conditions
Growth promotion
Health aspects
Hippocampus - cytology
Medical sciences
Neurons
Neurons - drug effects
Neurons - metabolism
Physiological aspects
Polychlorinated biphenyls
Polychlorinated Biphenyls - toxicity
Public health. Hygiene
Public health. Hygiene-occupational medicine
Rats
Receptors
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
Small interfering RNA
Toxicology
Vehicles
Weanlings
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: Aroclor 1254 (A1254) interferes with normal dendritic growth and plasticity in the developing rodent brain, but the mechanism(s) mediating this effect have yet to be established. Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) enhance the activity of ryanodine receptor (RyR) calcium ion (Ca²⁺) channels, which play a central role in regulating the spatiotemporal dynamics of intracellular Ca²⁺ signaling. Ca²⁺ signaling is a predominant factor in shaping dendritic arbors, but whether PCB potentiation of RyR activity influences dendritic growth is not known. Objective: We determined whether RyR activity is required for PCB effects on dendritic growth. Methods and Results: Golgi analysis of hippocampi from weanling rats confirmed that developmental exposure via the maternal diet to NDL PCB-95 (2,2',3,5'6-pentachlorobiphenyl), a potent RyR potentiator, phenocopies the dendrite-promoting effects of A1254. Dendritic growth in dissociated cultures of primary hippocampal neurons and in hippocampal slice cultures is similarly enhanced by PCB-95 but not by PCB-66 (2,3,4',4-tetrachlorobiphenyl), a congener with negligible effects on RyR activity. The dendrite-promoting effects of PCB-95 are evident at concentrations as low as 2 pM and are inhibited by either pharmacologie blockade or siRNA knockdown of RyRs. Conclusions: Our findings demonstrate that environmentally relevant levels of NDL PCBs modulate neuronal connectivity via RyR-dependent effects on dendritic arborization. In addition, these findings identify RyR channel dysregulation as a novel mechanism contributing to dysmorphic dendritogenesis associated with heritable and environmentally triggered neurodevelopmental disorders.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.1104832