Maternal milk as methylmercury source for suckling mice: neurotoxic effects involved with the cerebellar glutamatergic system.
Methylmercury (MeHg) is a highly neurotoxic compound and several studies have reported intoxication signs in children whose mothers were exposed to this environmental toxicant. Although it is well established that the in utero exposure to MeHg causes neurological deficits in animals and humans, there is no evidence of the exclusive contribution of lactational exposure to MeHg as a possible cause of neurotoxicity in the offspring. In this study, we investigated the exclusive contribution of MeHg exposure through maternal milk on biochemical parameters related to the glutamatergic homeostasis (glutamate uptake by slices) and to the oxidative stress (total and nonprotein sulfhydryl groups, nonprotein hydroperoxides, glutathione peroxidase and catalase activities) in the cerebellum of suckling mice (Swiss albino). The same parameters were also evaluated in the cerebellum of mothers. Our results showed, for the first time, that lactational exposure to MeHg caused a high percent of inhibition (50%) on glutamate uptake by cerebellar slices in pups. Contrarily, this effect was not observed in mothers, which were submitted to a direct oral exposure to MeHg (15 mg/l in drinking water). In addition, behavioral/functional changes were observed in the weaning mice exposed to MeHg. It was observed an increase in the levels of nonprotein hydroperoxides in cerebellum, and this increase was negatively correlated to the glutamate uptake by cerebellar slices. This study indicates that (1) the exposure of lactating mice to MeHg causes inhibition of the glutamate uptake by cerebellar slices in the offspring; (2) this inhibitory effect seems to be related to increased levels of hydroperoxide.
Manfroi
C B
CB
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.
Schwalm
F D
FD
Cereser
V
V
Abreu
F
F
Oliveira
A
A
Bizarro
L
L
Rocha
J B T
JB
Frizzo
M E S
ME
Souza
D O
DO
Farina
M
M
D000818:Animals; D000833:Animals, Suckling; D000975:Antioxidants / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008767:Methylmercury Compounds / Q000506:poisoning*; D051379:Mice; D008892:Milk / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000503:physiopathology* / Q000523:psychology; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D008767:Methylmercury Compounds; D009419:Nerve Tissue Proteins; D013438:Sulfhydryl Compounds; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase