Increased {beta}-amyloid levels in the choroid plexus following lead exposure and the involvement of low-density lipoprotein receptor protein-1
- School of Health Sciences, Purdue University, 550 Stadium Mall Drive, Room 1169, West Lafayette, IN 47907 (United States)
The choroid plexus, a barrier between the blood and cerebrospinal fluid (CSF), is known to accumulate lead (Pb) and also possibly function to maintain brain's homeostasis of A{beta}, an important peptide in the etiology of Alzheimer's disease. This study was designed to investigate if Pb exposure altered A{beta} levels at the blood-CSF barrier in the choroid plexus. Rats received ip injection of 27 mg Pb/kg. Twenty-four hours later, a FAM-labeled A{beta} (200 pmol) was infused into the lateral ventricle and the plexus tissues were removed to quantify A{beta} accumulation. Results revealed a significant increase in intracellular A{beta} accumulation in the Pb-exposed animals compared to controls (p < 0.001). When choroidal epithelial Z310 cells were treated with 10 {mu}M Pb for 24 h and 48 h, A{beta} (2 {mu}M in culture medium) accumulation was significantly increased by 1.5 fold (p < 0.05) and 1.8 fold (p < 0.05), respectively. To explore the mechanism, we examined the effect of Pb on low-density lipoprotein receptor protein-1 (LRP1), an intracellular A{beta} transport protein. Following acute Pb exposure with the aforementioned dose regimen, levels of LRP1 mRNA and proteins in the choroid plexus were decreased by 35% (p < 0.05) and 31.8% (p < 0.05), respectively, in comparison to those of controls. In Z310 cells exposed to 10 {mu}M Pb for 24 h and 48 h, a 33.1% and 33.4% decrease in the protein expression of LRP1 was observed (p < 0.05), respectively. Knocking down LRP1 resulted in even more substantial increases of cellular accumulation of A{beta}, from 31% in cells without knockdown to 72% in cells with LRP1 knockdown (p < 0.05). Taken together, these results suggest that the acute exposure to Pb results in an increased accumulation of intracellular A{beta} in the choroid plexus; the effect appears to be mediated, at least in part, via suppression of LRP1 production following Pb exposure.
- OSTI ID:
- 21272686
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 240, Issue 2; Other Information: DOI: 10.1016/j.taap.2009.05.024; PII: S0041-008X(09)00221-X; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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