Mehg-exposure through seafood consumption: Cholinergic muscarinic receptor as a target of toxicity and potential biomarker of CNS effects

Teresa Coccini, Elisa Roda, Anna F. Castoldi, Luigi Manzo

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Methylmercury (MeHg) highly bioaccumulates in marine and freshwater fish, biomagnifying in aquatic food webs. The dietary pathway, through the consumption of contaminated fish is the main source of human exposure. MeHg is efficiently absorbed and distributed throughout the body, including the CNS. Pervasive chronic low level Hg exposure, primarily through the widespread consumption of fish, is of concern because there is evidence that low-levels produce subtle neurodevelopmental disabilities. Cerebral cholinergic muscarinic receptors (MRs) are one of the sensitive biochemical CNS endpoints altered by MeHg-exposure. In vivo and in vitro experimental studies, aim at providing mechanistic insights involved in MeHg-induced neurotoxicity and pointing out potential biomarkers of CNS changes, investigated the effects of different doses and timing of MeHg exposure on brain and lymphocytes MRs in mature and immature rats. Cerebral data: (i) 1 mg MeHg/kg/day, gestational day(GD)7-post natal(PD)7, enhanced MRs more in dams (87% and 60% in cerebellum and cerebral cortex, respectively) than in PD21 pups (0-50%) in accordance with the higher Hg levels detected in the adult brain (7-9 μg/g) than in offspring's brain (1. 5-2. 8 μg/g); (ii) 0. 5 mg/kg/day (GD7- PD21) MeHg affected total MRs and M1, M2, and M3 subtypes of the mature and immature rats, in a brain-area-, gender- and time-dependent fashion, also causing reactive gliosis in the cerebellum. Lymphocyte data: 1 mg MeHg/kg/day (GD7-PD7) enhanced MR density in both mature and immature rats, with a more pronounced effect in mothers (Bmax - [density] increase of 139% over control) than in offspring (49-73%) as compared with their respective controls in accordance with the higher Hg levels detected in the adult blood (11. 3±2. 2 μg/mL) than in pups (1. 3±0. 4 μg/mL). In summary, the lymphocytes data mirrored those found in brain MRs confirming our previous results in non-pregnant adult rats that supported the predictive value of these peripheral receptors as surrogate markers of CNS changes. In vitro studies showed that MeHg was an almost equipotent inhibitor of the specific muscarinic50 range: 4. 1-5. 2 μM). Notably, IC50 values for MeHg to lymphocyte MRs were comparable to the Hg levels reached in blood (5-50 μM) of the PD21 rats exposed to MeHg. These findings show that MRs are a sensitive target of CNS in response to MeHg-exposure. The effect of MeHg in peripheral blood cells is in accordance with the data in brain, supporting the use of this peripheral endpoint as a potential biomarker of MeHg-induced cerebral muscarinic alterations. Furthermore, the similarity of MeHg IC50 binding data in human and animal peripheral tissues suggests the possible application of such biomarker to humans exposed to this environmental toxicant.

Original languageEnglish
Title of host publicationMethylmercury: Formation, Sources and Health Effects
PublisherNova Science Publishers, Inc.
Pages167-190
Number of pages24
ISBN (Print)9781617618383
Publication statusPublished - Feb 2011

ASJC Scopus subject areas

  • Environmental Science(all)

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