title: PCB-95 promotes dendritic growth via ryanodine receptor-dependent mechanisms.
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 (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.
  
  
  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.
authors.affiliation: Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Wayman
authors.forename: Dongren
authors.initials: D
authors.lastname: Yang
authors.forename: Diptiman D
authors.initials: DD
authors.lastname: Bose
authors.forename: Adam
authors.initials: A
authors.lastname: Lesiak
authors.forename: Veronica
authors.initials: V
authors.lastname: Ledoux
authors.forename: Donald
authors.initials: D
authors.lastname: Bruun
authors.forename: Isaac N
authors.initials: IN
authors.lastname: Pessah
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; C032904:2,2',3,5',6-pentachlorobiphenyl; D011078:Polychlorinated Biphenyls