Abstract
Methylmercury (MeHg) is a highly neurotoxic form of mercury (Hg) present in seafood. Here, we recorded and compared proteomic and transcriptomic changes in hippocampus of male BALB/c mice exposed to two doses of MeHg. Mice were fed diets spiked with 0.28 mg MeHg kg–1, 5 mg MeHg kg–1, or an unspiked control diet for 77 days. Total mercury content was significantly (P < 0.05) increased in brain tissue of both MeHg-exposed groups (18 ± 2 mg Hg kg–1 and 0.56 ± 0.06 mg Hg kg–1). Hippocampal protein and ribonucleic acid (RNA) expression levels were significantly altered both in tissues from mice receiving a low dose MeHg (20 proteins/294 RNA transcripts) and a high dose MeHg (61 proteins/876 RNA transcripts). The majority but not all the differentially expressed features in hippocampus were dose dependent. The combined use of transcriptomic and proteomic profiling data provided insight on the influence of MeHg on neurotoxicity, energy metabolism, and oxidative stress through several regulated features and pathways, including RXR function and superoxide radical degradation.
Highlights
The organic methylmercury (MeHg) originates from both natural and anthropogenic sources and is abundantly spread in the atmosphere and biosphere.[1,2,3,4] The compound biomagnifies along the aquatic food chain,[5] and the main exposure route of MeHg for humans is through seafood consumption.[6]
To explore how dietary MeHg influences protein and ribonucleic acid (RNA) expression in hippocampus, we sub-chronically exposed BALB/c mice to a low dose MeHg (LD; 0.28 mg Hg kg–1 feed, corresponding to ∼0.04 mg MeHg kg–1 bw–1 day–1), a high dose MeHg (HD; 5 mg Hg kg–1 feed corresponding to ∼0.67 mg MeHg kg–1 bw–1 day–1), or an unspiked control feed (Ctr)
In this study, using transcriptomic and proteomic analyses of hippocampus from BALB/c mice, we demonstrate that known effects of MeHg, such as differentially expressed genes and proteins indicative of inflammation, metabolism, and neurotoxicity, are present at both low dose of MeHg (0.28 mg Hg kg–1 feed) and high dose of MeHg exposure (5 mg Hg kg–1 feed)
Summary
The organic methylmercury (MeHg) originates from both natural and anthropogenic sources and is abundantly spread in the atmosphere and biosphere.[1,2,3,4] The compound biomagnifies along the aquatic food chain,[5] and the main exposure route of MeHg for humans is through seafood consumption.[6]. Japan and Iraq where levels of exposure to MeHg were high[12,13,14,15,16,17]; the levels of MeHg in most consumed commercial fish species are often relatively low.[11] Further, MeHg exposure exerts a non-monotonic dose response rather than a linear dose response.[18,19] effects reported at low exposure doses in animal trials are not necessarily observed at high doses of MeHg exposure.[18,19] The European Food Safety Authority (EFSA) did in their latest evaluation of MeHg establish a tolerable weekly intake level for MeHg at 1.3 μg kg–1 bw (EFSA 2012). Since recent studies discuss the validity of such a threshold dose, research on low dose effect of MeHg is required
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