Dietary selenium protects against selected signs of aging and methylmercury exposure.
Acute or short-term exposure to high doses of methylmercury (MeHg) causes a well-characterized syndrome that includes sensory and motor deficits. The environmental threat from MeHg, however, comes from chronic, low-level exposure, the consequences of which are poorly understood. Selenium (Se), an essential nutrient, both increases deposition of mercury (Hg) in neurons and mitigates some of MeHg's neurotoxicity in the short term, but it is unclear whether this deposition produces long-term adverse consequences. To investigate these issues, adult Long-Evans rats were fed a diet containing 0.06 or 0.6 ppm of Se as sodium selenite. After 100 days on these diets, the subjects began consuming 0.0, 0.5, 5.0, or 15 ppm of Hg as methylmercuric chloride in their drinking water for 16 months. Somatosensory sensitivity, grip strength, hindlimb cross (clasping reflex), flexion, and voluntary wheel-running in overnight sessions were among the measures examined. MeHg caused a dose- and time-dependent impairment in all measures. No effects appeared in rats consuming 0 or 0.5 ppm of Hg. Somatosensory function, grip strength, and flexion were among the earliest signs of exposure. Selenium significantly delayed or blunted MeHg's effects. Selenium also increased running in unexposed animals as they aged, a novel finding that may have important clinical implications. Nerve pathology studies revealed axonal atrophy or mild degeneration in peripheral nerve fibers, which is consistent with abnormal sensorimotor function in chronic MeHg neurotoxicity. Lidocaine challenge reproduced the somatosensory deficits but not hindlimb cross or flexion. Together, these results quantify the neurotoxicity of long-term MeHg exposure, support the safety and efficacy of Se in ameliorating MeHg's neurotoxicity, and demonstrate the potential benefits of Se during aging.
Heath
John C
JC
Experimental Psychology, Auburn University, Auburn, AL 36849, USA. john.heath@tuskegee.edu
Banna
Kelly M
KM
Reed
Miranda N
MN
Pesek
Erin F
EF
Cole
Nathan
N
Li
Jun
J
Newland
M Christopher
MC
D000375:Aging / Q000187:drug effects*; D000818:Animals; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005260:Female; D018737:Hand Strength; D008012:Lidocaine / Q000494:pharmacology; D020262:Mercury Poisoning, Nervous System / Q000178:diet therapy* / Q000401:mortality / Q000473:pathology; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D018036:Selenium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012684:Sensory Thresholds / Q000187:drug effects; D013997:Time Factors
D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D018036:Selenium Compounds; D008012:Lidocaine; C004925:methylmercuric chloride