Chronic lead exposure alters transthyretin concentration in rat cerebrospinal fluid: the role of the choroid plexus.
The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones.
Zheng
W
W
Division of Environmental Health Sciences, School of Public Health, New York, New York, USA.
Shen
H
H
Blaner
W S
WS
Zhao
Q
Q
Ren
X
X
Graziano
J H
JH
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002413:Cations, Divalent / Q000134:cerebrospinal fluid / Q000378:metabolism; D002414:Cations, Monovalent / Q000134:cerebrospinal fluid / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008670:Metals / Q000134:cerebrospinal fluid; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011228:Prealbumin / Q000032:analysis / Q000134:cerebrospinal fluid*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002413:Cations, Divalent; D002414:Cations, Monovalent; D008670:Metals; D009942:Organometallic Compounds; D011228:Prealbumin; D007854:Lead; C008261:lead acetate