PCB-95 Promotes Dendritic Growth via Ryanodine Receptor–Dependent Mechanisms
| العنوان: | PCB-95 Promotes Dendritic Growth via Ryanodine Receptor–Dependent Mechanisms |
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| المؤلفون: | Adam Lesiak, Dongren Yang, Donald A. Bruun, Pamela J. Lein, Diptiman D. Bose, Isaac N. Pessah, Gary A. Wayman, Veronica Ledoux |
| المصدر: | Environmental Health Perspectives |
| بيانات النشر: | National Institute of Environmental Health Sciences, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | medicine.medical_specialty, dendrites, Health, Toxicology and Mutagenesis, hippocampal neurons, Hippocampus, Biology, neuronal connectivity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, ryanodine receptor, Animals, Cells, Cultured, 030304 developmental biology, Developmental neurotoxicity, Neurons, 0303 health sciences, Extramural, Ryanodine receptor, Mechanism (biology), Research, Public Health, Environmental and Occupational Health, Ryanodine Receptor Calcium Release Channel, Polychlorinated Biphenyls, Cell biology, Rats, Endocrinology, developmental neurotoxicity, non-dioxin-like PCBs, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1552-9924 0091-6765 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::848da53d0f11efd81cdfe5c3aa8aefaa http://europepmc.org/articles/PMC3404670 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....848da53d0f11efd81cdfe5c3aa8aefaa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15529924 00916765 |
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