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Effect of methylmercury administration on choroid plexus function in rats

  • Inorganic Compounds
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Abstract

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 (Qalb), 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 Qalb 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, Qalb 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.

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Abbreviations

BBB:

blood–brain barrier

BCSFB:

blood–CSF barrier

CNS:

central nervous system

CP:

choroid plexus

CSF:

cerebrospinal fluid

Ct:

threshold cycles

GFAP:

glial fibrillary acidic protein

MeHg:

methylmercury

MUSTag:

Multiple Simultaneous Tag

Qalb :

CSF/plasma concentration quotient

RT-PCR:

reverse transcriptase-polymerase chain reaction

SELDI-TOF–MS:

surface-enhanced laser desorption ionization-time-of-flight-mass spectrometry

TTR:

transthyretin

TUNEL:

terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

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Acknowledgments

The authors thank Ms. N. Tabata, Ms. M. Ogata, and Ms. A. Onitsuka for their technical assistance in various analyses. The experimental protocol was approved by the Ethics Committee for Research on Animals at the National Institute for Minamata Disease.

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Authors and Affiliations

  1. Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, Minamata, 867-0008, Japan

    Masaaki Nakamura

  2. Department of Basic Medical Sciences, National Institute for Minamata Disease, 4058-18 Hama, Minamata, 867-0008, Japan

    Akira Yasutake, Masatake Fujimura & Masumi Marumoto

  3. Department of International Affairs and Environmental Sciences, National Institute for Minamata Disease, 4058-18 Hama, Minamata, 867-0008, Japan

    Noriyuki Hachiya

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  1. Masaaki Nakamura
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  2. Akira Yasutake
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  3. Masatake Fujimura
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  4. Noriyuki Hachiya
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  5. Masumi Marumoto
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Correspondence to Masaaki Nakamura.

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Nakamura, M., Yasutake, A., Fujimura, M. et al. Effect of methylmercury administration on choroid plexus function in rats. Arch Toxicol 85, 911–918 (2011). https://doi.org/10.1007/s00204-010-0623-8

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  • DOI: https://doi.org/10.1007/s00204-010-0623-8

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