PubMed日本語 - PCB-95は、リアノジン受容体依存的な機序で樹状突起の発育を促進する。―QLifePro医療翻訳医療翻訳 QLifePro


PCB-95 promotes dendritic growth via ryanodine receptor-dependent mechanisms.


Published date



Gary A Wayman, Dongren Yang, Diptiman D Bose, Adam Lesiak, Veronica Ledoux, Donald Bruun, Isaac N Pessah, Pamela J Lein


Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USA.


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 (Ca(2+)) channels, which play a central role in regulating the spatiotemporal dynamics of intracellular Ca(2+) signaling. Ca(2+) 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.


背景Aroclor 1254(A1254)は発育過程の齧歯目の脳で正常な樹状突起の発育と可塑性に干渉する、しかし、この効果の媒介となっている機構はまだ確立されていない。


方法と結果:離乳したての動物ラットからのヒッポカンポスのゴルジ分析は、母性ものを経た発達上の暴露がNDL PCB-95(2,2',3,5'6-ペンタクロロビフェニル)、強力なRyR強化剤、フェノコピーにA1254の樹状突起を促進している効果に食物を与えることを確認した。

結論:我々の所見は、NDL PCBの環境的に関連したレベルが樹状突起の樹枝状に対するRyR依存的な効果を経てニューロン連結性を調整することを証明する。

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