Parent A S, Pinson A, Woods N, Chatzi C, Vaaga C E, Bensen A, Gérard A, Thome J P, Bourguignon J P, Westbrook G L
Neuroendocrinology Unit, GIGA-N, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium.
Vollum Institute, Portland, OR, USA.
Eur J Neurosci. 2016 Dec;44(12):3001-3010. doi: 10.1111/ejn.13437. Epub 2016 Nov 2.
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.
齿状回中的神经发生对影响海马功能的内源性和外源性因素敏感。因此,持续的神经发生以及这些新神经元在整个生命过程中的整合可能提供环境应激的敏感指标。我们研究了多氯联苯(PCBs)混合物Aroclor 1254(A1254)对新生成的齿状颗粒细胞发育和功能的影响。早期接触A1254与儿童学习障碍有关,提示其对海马和/或皮质回路发育有潜在影响。口服A1254(从妊娠第6天至出生后第21天)在出生后第21天使脑中PCB水平出现预期升高,并在成年期维持在较低水平。A1254不影响未成熟动物新生神经元的增殖或存活,也未引起神经元形态的明显变化。然而,A1254在有丝分裂后第三周阻断了sEPSC频率的正常发育性增加,而未改变平均sEPSC幅度。我们的结果表明,早期接触PCBs可在活跃的突触发生期破坏兴奋性突触功能,从而可能导致接触PCBs儿童出现认知效应。