Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat.
Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic ((i)As) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of (i)As (0.05, 0.5 mg (i)As/L) and to a high dose (50 mg (i)As/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50 mg (i)As/L. Exposure to 0.5 and 50 mg (i)As/L increased the total brain content of As. Furthermore, (i)As exposure produced a dose-dependent up-regulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D₂ mRNA levels in the nucleus accumbens. DAR-D₁ and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50 mg (i)As/L. Trx-1 mRNA levels were up-regulated in the cortex in an (i)As dose-dependent manner, while DAR-D₁ mRNA expression was increased in striatum in the 0.5 mg (i)As/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50 mg (i)As/L.
Rodríguez
Verónica Mireya
VM
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Querétaro, Querétaro 76230, México. vermire@yahoo.com
Limón-Pacheco
Jorge Humberto
JH
Carrizales
Leticia
L
Mendoza-Trejo
María Soledad
MS
Giordano
Magda
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D018053:Arsenites / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000235:genetics; D017670:Sodium Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000235:genetics; D013879:Thioredoxins / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity*
D000975:Antioxidants; D018053:Arsenites; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D011954:Receptors, Dopamine; D017670:Sodium Compounds; C495697:Txn1 protein, rat; D014874:Water Pollutants, Chemical; D012701:Serotonin; C017947:sodium arsenite; D013879:Thioredoxins; D012313:RNA; D013482:Superoxide Dismutase