Early lead exposure increases the leakage of the blood-cerebrospinal fluid barrier, in vitro.
The cell type constructing the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCB) is entirely different, ie, endothelia in BBB and epithelia in BCB. Nonetheless, both barriers share a common character--the tight junctions (TJ) between adjacent cells. This study investigated the consequence of lead (Pb) exposure on the tightness of BCB. In an in vitro BCB transwell model, using immortalized choroidal epithelial Z310 cells, we found that early exposure to Pb (prior to the formation of tight barrier) at 5 and 10 microM, significantly reduced the tightness of BCB, as evidenced by a 20% reduction in transepithelial electrical resistance (TEER) values (P <0.05), and >20% increase in the paracellular permeability of [(14)C]sucrose (P <0.05). Exposure to Pb after the formation of tight barrier, however, did not cause any detectable barrier dysfunction. RT-PCR and Western blot analyses on typical TJ proteins revealed that Pb exposure decreased both the mRNA and protein levels of claudin-1, with the membrane-bound claudin-1 more profoundly affected than cytosolic claudin-1. Pb exposure, however, had no significant effect on ZO1 and occludin. These data suggest that Pb exposure selectively alters the cellular level of claudin-1, which, in turn, reduces the tightness and augments the permeability of tight blood-CSF barrier. The immature barrier appears to be more vulnerable to Pb toxicity than the mature, well-developed, brain barrier, the fact possibly contributing to Pb-induced neurotoxicity among young children.
Shi
Lewis Zhichang
LZ
School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Zheng
Wei
W
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002555:Cerebrospinal Fluid / Q000502:physiology*; D002831:Choroid Plexus / Q000166:cytology; D062445:Claudin-1; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D007854:Lead / Q000633:toxicity*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D010539:Permeability / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013395:Sucrose / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology; D062826:Zonula Occludens-1 Protein
D062445:Claudin-1; C568114:Cldn1 protein, rat; D004785:Environmental Pollutants; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D007854:Lead; D013395:Sucrose