![]() Polychlorinated biphenyls (PCBs) are known human developmental neurotoxicants ( Carpenter 2006 Korrick and Sagiv 2008 Schantz et al. Abnormalities in dendritic shape are the most consistent pathologic correlate of behavioral deficits in heritable and environmentally triggered neurodevelopmental disorders ( Bourgeron 2009 Fukuda et al. In addition, these findings identify RyR channel dysregulation as a novel mechanism contributing to dysmorphic dendritogenesis associated with heritable and environmentally triggered neurodevelopmental disorders.ĭendritic architecture is a critical determinant of neuronal connectivity ( Libersat and Duch 2004 Scott and Luo 2001). 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.Ĭonclusions: Our findings demonstrate that environmentally relevant levels of NDL PCBs modulate neuronal connectivity via RyR-dependent effects on dendritic arborization. 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. 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♆-pentachlorobiphenyl), a potent RyR potentiator, phenocopies the dendrite-promoting effects of A1254. Objective: We determined whether RyR activity is required for PCB effects on dendritic growth. Ca 2+ signaling is a predominant factor in shaping dendritic arbors, but whether PCB potentiation of RyR activity influences dendritic growth is not known. 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. 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.
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