CoChat
Sign Up
Cited by 136Toxic Organic Pollutants ImpactNeuroscience and Neuropharmacology ResearchEffects and risks of endocrine disrupting chemicals

The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.

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

Open access
Wayman, Gary A., Yang, Dongren, Bose, Diptiman D., Lesiak, Adam, Ledoux, Veronica, Bruun, Donald, Pessah, Isaac N., Lein, Pamela J.·2012·Environmental Health Perspectives
DOI 10.1289/ehp.1104832PMC PMC3404670
Open this paper in CoChat — free account

Abstract

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 pharmacologic 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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1289/ehp.1104832

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 PCBs enhance dendritic growth in vivo. (A) Representative camera lucida images and (B) Sholl analyses of the basilar dendritic arbor of Golgi-stained CA1 pyramidal neurons from PD31 weanling rats exposed throughout gestation and lactation to vehicle or A1254 in the maternal diet (n = 45 neurons per group). (C) Sholl analyses of the basilar dendritic arbor of Golgi-stained pyramidal neurons from PD38 weanling rats exposed throughout gestation and lactation to vehicle or PCB-95 in the maternal diet (n = 60 neurons per group). *p < 0.05 relative to vehicle control.
Figure 1 PCBs enhance dendritic growth in vivo. (A) Representative camera lucida images and (B) Sholl analyses of the basilar dendritic arbor of Golgi-stained CA1 pyramidal neurons from PD31 weanling rats exposed throughout gestation and lactation to vehicle or A1254 in the maternal diet (n = 45 neurons per group). (C) Sholl analyses of the basilar dendritic arbor of Golgi-stained pyramidal neurons from PD38 weanling rats exposed throughout gestation and lactation to vehicle or PCB-95 in the maternal diet (n = 60 neurons per group). *p < 0.05 relative to vehicle control.CC0 · PubMed Central
Figure 2 RyR expression in cultured hippocampal neurons. (A) Representative blots and densitometric analyses of membrane fractions from rat hippocampal cultures harvested at 2, 7, and 12 DIV, and probed with RyR1- or RyR2-selective monoclonal antibodies and a monoclonal antibody for α-tubulin. Densitometric data are presented as the pixel intensity of the RyR-immunoreactive band normalized to the pixel intensity of the α-tubulin immunoreactive band in the same sample. Expression of RyR1 and RyR2 at 7 and 12 DIV was verified in cultures derived from two separate dissections. “Brain” indicates membranes prepared from adult (2- to 4-month-old) mouse hippocampi. (B) Fluorescent photomicrograph illustrating subcellular localization of RyR immunoreactivity (red) and phalloidin reactivity (green) in a 21-DIV mouse hippocampal neuron. Bar = 5 μM.
Figure 2 RyR expression in cultured hippocampal neurons. (A) Representative blots and densitometric analyses of membrane fractions from rat hippocampal cultures harvested at 2, 7, and 12 DIV, and probed with RyR1- or RyR2-selective monoclonal antibodies and a monoclonal antibody for α-tubulin. Densitometric data are presented as the pixel intensity of the RyR-immunoreactive band normalized to the pixel intensity of the α-tubulin immunoreactive band in the same sample. Expression of RyR1 and RyR2 at 7 and 12 DIV was verified in cultures derived from two separate dissections. “Brain” indicates membranes prepared from adult (2- to 4-month-old) mouse hippocampi. (B) Fluorescent photomicrograph illustrating subcellular localization of RyR immunoreactivity (red) and phalloidin reactivity (green) in a 21-DIV mouse hippocampal neuron. Bar = 5 μM.CC0 · PubMed Central
Figure 3 PCB-95 enhances dendritic growth in cultured hippocampal neurons. (A) Representative photomicrographs of 9-DIV hippocampal neurons expressing MAP2B-EGFP after 48-hr exposure to vehicle (control) or PCB-95 (2 nM). (B) Concentration-dependent effect of PCB-95 on dendritic length and branching (determined as the number of dendritic termini per neuron) in GFP+ neurons. Data presented as mean ± SE (n = 30 neurons from three to four independent cultures per group). #p < 0.001 relative to vehicle control.
Figure 3 PCB-95 enhances dendritic growth in cultured hippocampal neurons. (A) Representative photomicrographs of 9-DIV hippocampal neurons expressing MAP2B-EGFP after 48-hr exposure to vehicle (control) or PCB-95 (2 nM). (B) Concentration-dependent effect of PCB-95 on dendritic length and branching (determined as the number of dendritic termini per neuron) in GFP+ neurons. Data presented as mean ± SE (n = 30 neurons from three to four independent cultures per group). #p < 0.001 relative to vehicle control.CC0 · PubMed Central
Figure 4 In vitro PCB-induced dendritic growth requires RyR activity. PCB-95 (200 nM), but not PCB-66 (200 nM), increased dendritic length (A) and branching (B) in primary cultures of dissociated hippocampal neurons (9 DIV), and this effect was blocked by the RyR antagonist FLA365 (10 µM) (–, without, +, with FLA365). (C) PCB-95, but not PCB-66, significantly enhanced dendritic arborization of TFP+ neurons in hippocampal slice cultures, and this effect was blocked by FLA365. Data presented as mean ± SE (n = 35–50 neurons from three to four independent cultures per group). *p < 0.05, **p < 0.01, and #p < 0.001 relative to vehicle control. †p < 0.01 relative to PCB-95 in the absence of FLA365.
Figure 4 In vitro PCB-induced dendritic growth requires RyR activity. PCB-95 (200 nM), but not PCB-66 (200 nM), increased dendritic length (A) and branching (B) in primary cultures of dissociated hippocampal neurons (9 DIV), and this effect was blocked by the RyR antagonist FLA365 (10 µM) (–, without, +, with FLA365). (C) PCB-95, but not PCB-66, significantly enhanced dendritic arborization of TFP+ neurons in hippocampal slice cultures, and this effect was blocked by FLA365. Data presented as mean ± SE (n = 35–50 neurons from three to four independent cultures per group). *p < 0.05, **p < 0.01, and #p < 0.001 relative to vehicle control. †p < 0.01 relative to PCB-95 in the absence of FLA365.CC0 · PubMed Central
Figure 5 RyR-specific siRNA blocks PCB-induced dendritic growth in vitro. (A) Representative photomicrographs of 9-DIV hippocampal neurons transfected with MAP2B-EGFP alone or in combination with RyR siRNA before 48-hr treatment with vehicle or PCB-95 (200 nM). Expression of RyR1- or RyR2-specific siRNA, but not scrambled siRNA, blocked PCB-95 effects on dendritic length (B) and branching (C). Data presented as mean ± SE (n = 30 neurons from three independent cultures per group). **p < 0.01 relative to vehicle control. ‡p < 0.001 relative to untransfected (control) PCB-95–treated hippocampal neurons.
Figure 5 RyR-specific siRNA blocks PCB-induced dendritic growth in vitro. (A) Representative photomicrographs of 9-DIV hippocampal neurons transfected with MAP2B-EGFP alone or in combination with RyR siRNA before 48-hr treatment with vehicle or PCB-95 (200 nM). Expression of RyR1- or RyR2-specific siRNA, but not scrambled siRNA, blocked PCB-95 effects on dendritic length (B) and branching (C). Data presented as mean ± SE (n = 30 neurons from three independent cultures per group). **p < 0.01 relative to vehicle control. ‡p < 0.001 relative to untransfected (control) PCB-95–treated hippocampal neurons.CC0 · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 59 references

Cited by

Sorted by citations

Items 101–136 of 136

Related

See all

Metadata

Authors
Wayman, G. A., Yang, D., Bose, D. D., Lesiak, A., Ledoux, V., Bruun, D., Pessah, I. N., & Lein, P. J.
Affiliations
  • Washington State University (US)
  • University of California, Davis (US)
  • Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USA
  • Oregon Health & Science University (US)
Corresponding author
Lein, Pamela J.
ORCID
Venue
Environmental Health Perspectives
Publisher
American Chemical Society (ACS)
Published
2012-04-25
Volume
120
Issue
7
Pages
997-1002
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
DOI
10.1289/ehp.1104832
PMC
PMC3404670
OpenAlex
W2057153652
Cited by
136
References
59
Citations by year
2026: 7 · 2025: 2 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 6 · 2020: 12 · 2019: 14 · 2018: 12 · 2017: 12 · 2016: 8 · 2015: 3 · 2014: 12 · 2013: 15 · 2012: 5
FWCI
7.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • U.S. Environmental Protection Agency (R-829388, R-833292, R01 ES014901, ES011269)
  • Hope for Depression Research Foundation
  • National Institutes of Health (ES04699, ES014901, ES011269)
  • National Institute of Mental Health (R01MH086032)
  • National Institute of Environmental Health Sciences (P42-ES-04699, P42ES004699, R01ES017425, P01ES011269, R01ES014901, T32ES007060)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords
PCB 95, non-dioxin-like polychlorinated biphenyls, ryanodine receptor, dendritic growth, dendritic branching, calcium signaling, Aroclor 1254, hippocampal neurons, neurodevelopmental disorders, developmental neurotoxicity, PCB congeners, maternal dietary exposure
MeSH terms
Animals, Cells, Cultured, Dendrites, Hippocampus, Neurons, Polychlorinated Biphenyls, Ryanodine Receptor Calcium Release Channel, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review