Which mercury species crosses the blood–brain barrier readily, contributing to CNS effects?

• A. Methylmercury
• B. Inorganic mercury
• C. Ethylmercury
• D. Metallic mercury

Answer: (A)

Crossing the blood–brain barrier depends on lipophilicity and how the compound can ride on transporters that ferry nutrients into the brain. Methylmercury forms a neutral complex with cysteine, so it essentially masquerades as the amino acid methionine. This complex is recognized by the large neutral amino acid transporter at the blood–brain barrier, allowing it to enter the CNS readily. Once inside, methylmercury binds to thiol groups in proteins and to selenoenzymes, disrupting neuronal function and promoting oxidative stress, which underlies the CNS toxicity seen with this form. Inorganic mercury is not very lipophilic and crosses poorly, metallic mercury can enter as vapor but does not accumulate in the brain to the same extent, and ethylmercury, while it can cross, is eliminated more rapidly and causes less persistent CNS exposure. Therefore, methylmercury best explains the readily crossing into the brain and the associated CNS effects.