title: Early exposure to Aroclor 1254 in vivo disrupts the functional synaptic development of newborn hippocampal granule cells.
abstract: Neurogenesis in the dentate gyrus is sensitive to endogenous and exogenous factors that influence hippocampal function. Ongoing neurogenesis and the integration of these new neurons throughout life thus may provide a sensitive indicator of environmental stress. We examined the effects of Aroclor 1254 (A1254), a mixture of polychlorinated biphenyls (PCBs), on the development and function of newly generated dentate granule cells. Early exposure to A1254 has been associated with learning impairment in children, suggesting potential impact on the development of hippocampus and/or cortical circuits. Oral A1254 (from the 6th day of gestation to postnatal day 21) produced the expected increase in PCB levels in brain at postnatal day 21, which persisted at lower levels into adulthood. A1254 did not affect the proliferation or survival of newborn neurons in immature animals nor did it cause overt changes in neuronal morphology. However, A1254 occluded the normal developmental increase in sEPSC frequency in the third post-mitotic week without altering the average sEPSC amplitude. Our results suggest that early exposure to PCBs can disrupt excitatory synaptic function during a period of active synaptogenesis, and thus could contribute to the cognitive effects noted in children exposed to PCBs.
authors.affiliation: Neuroendocrinology Unit, GIGA-N, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium.
authors.forename: A S
authors.initials: AS
authors.lastname: Parent
authors.affiliation: Neuroendocrinology Unit, GIGA-N, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Pinson
authors.affiliation: Vollum Institute, Portland, OR, USA.
authors.forename: N
authors.initials: N
authors.lastname: Woods
authors.affiliation: Vollum Institute, Portland, OR, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chatzi
authors.affiliation: Vollum Institute, Portland, OR, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Vaaga
authors.affiliation: Vollum Institute, Portland, OR, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bensen
authors.affiliation: Neuroendocrinology Unit, GIGA-N, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Gérard
authors.affiliation: Laboratory of Animal Ecology and Ecotoxicology, University of Liège, Liège, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Thome
authors.affiliation: Neuroendocrinology Unit, GIGA-N, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Bourguignon
authors.affiliation: Vollum Institute, Portland, OR, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Westbrook
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D013963:Thyroid Hormones; D020111:Chlorodiphenyl (54% Chlorine)
keywords: PCBs; critical period; hippocampus; neurogenesis; synapse formation