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 bi ochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters P b. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were expos ed to Pb in drinking water at doses of 0, 50, or 250 mu g Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus w as assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF esse ntial metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were de termined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absor ption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revea led 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 concentratio ns of Ca2+, K+, and Na+. Histopathologic examination under the light m icroscope did not show distinct alterations of plexus structure in Pb- treated rats. Since TTR is responsible for transport of thyroid hormon es to the developing brain, we postulate that the depression of choroi d plexus TTR production (and/or secretion) by Pb may impair brain deve lopment in young animals by depriving the CNS of thyroid hormones. (C) 1996 Academic Press, Inc.