Effect of methylmercury administration on choroid plexus function in rats.
Methylmercury (MeHg) is a well-known environmental neurotoxin. The choroid plexus (CP), the main component of the blood-cerebrospinal fluid (CSF) barrier (BCSFB), protects the brain from xenobiotics, similar to the blood-brain barrier. Because CP is considered a critical target site of MeHg-induced neurotoxic damage, functional alterations in CP may be caused in relation to the extent of MeHg-induced brain injury. To test this hypothesis, we examined time-dependent pathological alterations in rats administered subtoxic (asymptomatic group) or toxic (symptomatic group) MeHg doses for 3 weeks after the cessation of MeHg administration. We primarily assessed (1) mercury concentrations in the brain, CSF, and plasma; (2) histopathological changes in the brain; (3) albumin CSF/plasma concentration quotient (Q(alb)), an index of BCSFB dysfunction; and (4) concentration of CSF transthyretin (TTR), which is primarily produced in CP. Mercury concentrations in the brain, CSF, and plasma decreased, and Q(alb) and CSF TTR concentrations did not change significantly in the asymptomatic group. In the symptomatic group, brain and CSF mercury concentrations did not decrease for 2 weeks after the cessation of MeHg administration, but no pathological alteration occurred in the brain during this period. Pathological changes in the cerebellum became evident 3 weeks after the cessation of MeHg administration. Furthermore, Q(alb) continued to increase after the cessation of MeHg administration, whereas no decrease in CSF TTR concentration was observed, indicating selective impairment of CP function. These findings suggest that MeHg at toxic doses causes selective functional alteration of CP before leading to pathological alterations in the brain.
Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, Minamata 867-0008, Japan. nakamura@nimd.go.jp
Masaaki
M
Nakamura
Akira
A
Yasutake
Masatake
M
Fujimura
Noriyuki
N
Hachiya
Masumi
M
Marumoto
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution
D008767:Methylmercury Compounds; C004925:methylmercuric chloride