Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice

• Published in: Toxicology and applied pharmacology 2009-09, Vol.239 (2), p.169-177
• Main Authors: Bardullas, U., Limón-Pacheco, J.H., Giordano, M., Carrizales, L., Mendoza-Trejo, M.S., Rodríguez, V.M.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; ANTIOXIDANTS; ARSENIC; Arsenites - toxicity; Biological and medical sciences; BRAIN; Brain - drug effects; Brain - enzymology; Brain - metabolism; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Chemical and industrial products toxicology. Toxic occupational diseases; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Cytosol - enzymology; Cytosol - metabolism; DOPAMINE; Dopamine - metabolism; Dose-Response Relationship, Drug; DOSES; Down-Regulation; DRINKING WATER; Environmental Pollutants - toxicity; Female; FEMALES; HUMAN POPULATIONS; HYDROXYLASES; Hypothalamus - drug effects; Hypothalamus - metabolism; Male; MALES; Medical sciences; Metals and various inorganic compounds; MICE; Mice, Inbred C57BL; Motor Activity - drug effects; NEOPLASMS; Nucleus accumbens; OXIDATION; Sex Factors; SKIN; Sodium Compounds - toxicity; Stereotypy; Striatum; Thioredoxins - biosynthesis; Time Factors; TOXICITY; Toxicology; Tumors; TYROSINE; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2008.12.004

Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.