TitleDevelopmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats.
Publication TypeJournal Article
Year of Publication2009
AuthorsYang D, Kim K H, Phimister A, Bachstetter AD, Ward TR, Stackman RW, Mervis RF, Wisniewski AB, Klein SL, Kodavanti P RS, Anderson KA, Wayman G, Pessah IN, Lein PJ
JournalEnviron Health Perspect
Date Published03/2009
Animals, Animals, Newborn, Body Weight, Chlorodiphenyl (54% Chlorine), Dendrites, Female, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Litter Size, Maze Learning, Memory, Microtubule-Associated Proteins, Neuronal Plasticity, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Rats, Sprague-Dawley, Ryanodine Receptor Calcium Release Channel, Sex Ratio

BACKGROUND: Neurodevelopmental disorders are associated with altered patterns of neuronal connectivity. A critical determinant of neuronal connectivity is the dendritic morphology of individual neurons, which is shaped by experience. The identification of environmental exposures that interfere with dendritic growth and plasticity may, therefore, provide insight into environmental risk factors for neurodevelopmental disorders.

OBJECTIVE: We tested the hypothesis that polychlorinated biphenyls (PCBs) alter dendritic growth and/or plasticity by promoting the activity of ryanodine receptors (RyRs).

METHODS AND RESULTS: The Morris water maze was used to induce experience-dependent neural plasticity in weanling rats exposed to either vehicle or Aroclor 1254 (A1254) in the maternal diet throughout gestation and lactation. Developmental A1254 exposure promoted dendritic growth in cerebellar Purkinje cells and neocortical pyramidal neurons among untrained animals but attenuated or reversed experience-dependent dendritic growth among maze-trained littermates. These structural changes coincided with subtle deficits in spatial learning and memory, increased [3H]-ryanodine binding sites and RyR expression in the cerebellum of untrained animals, and inhibition of training-induced RyR upregulation. A congener with potent RyR activity, PCB95, but not a congener with negligible RyR activity, PCB66, promoted dendritic growth in primary cortical neuron cultures and this effect was blocked by pharmacologic antagonism of RyR activity.

CONCLUSIONS: Developmental exposure to PCBs interferes with normal patterns of dendritic growth and plasticity, and these effects may be linked to changes in RyR expression and function. These findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling.

Alternate JournalEnviron. Health Perspect.
PubMed ID19337518
PubMed Central IDPMC2661913
Grant List1P01ES11269 / ES / NIEHS NIH HHS / United States
GM041292 / GM / NIGMS NIH HHS / United States
HD40936 / HD / NICHD NIH HHS / United States
NS046649 / NS / NINDS NIH HHS / United States
P01 ES011269 / ES / NIEHS NIH HHS / United States
R01 ES014901 / ES / NIEHS NIH HHS / United States
R01 NS046649 / NS / NINDS NIH HHS / United States
R03 HD040936 / HD / NICHD NIH HHS / United States