The present findings demonstrate that an individual PCB congener known to widely contaminate human populations can alter the course of neural differentiation in primary NHNP cells.
NHNP cells, which have the ability to differentiate into the three major cell types of the human brain--neurons, astrocytes, and oligodendrocytes (Figure 2)--formed the basis of this model.
Two important features of our in vitro model support their use in studies of chemical exposure on neurodevelopment: their xenobiotic metabolic capacity and their TH signal transduction machinery, mRNA analyses reveal that NHNP cells express a variety of phase 1 and phase 2 enzymes (Figure 3), which indicates that the cell may be capable of xenobiotic metabolism.
2], as well as all RAR and RXR isoforms, with exception of RARg, were present in NHNP cells.
In the present study, we found that the mono-ortho-substituted PCB-118, as well as TH, leads to an increased formation of oligodendrocytes in NHNP cells.
In another approach to investigate whether PCB-118 acts through the TR complex, we cotreated NHNP cells with RA.
However, the observed effect is congener specific because PCB-126 did not increase oligodendrocytes in NHNP cells.
We identified the mono-ortho-substituted PCB-118 as a TH disrupter on human neural development because it induced oligodendrocyte formation in NHNP cells.