Moderate perinatal arsenic exposure alters neuroendocrine markers associated with depression and increases depressive-like behaviors in adult mouse offspring.
Arsenic is one of the most common heavy metal contaminants found in the environment, particularly in water. We examined the impact of perinatal exposure to relatively low levels of arsenic (50 parts per billion, ppb) on neuroendocrine markers associated with depression and depressive-like behaviors in affected adult C57BL/6J mouse offspring. Whereas most biomedical research on arsenic has focused on its carcinogenic potential, a few studies suggest that arsenic can adversely affect brain development and neural function. Compared to controls, offspring exposed to 50 parts per billion arsenic during the perinatal period had significantly elevated serum corticosterone levels, reduced whole hippocampal CRFR 1 protein level and elevated dorsal hippocampal serotonin 5HT 1A receptor binding and receptor-effector coupling. 5HT 1A receptor binding and receptor-effector coupling were not different in the ventral hippocampal formation, entorhinal or parietal cortices, or inferior colliculus. Perinatal arsenic exposure also significantly increased learned helplessness and measures of immobility in a forced swim task. Taken together, these results suggest that perinatal arsenic exposure may disrupt the regulatory interactions between the hypothalamic-pituitary-adrenal axis and the serotonergic system in the dorsal hippocampal formation in a manner that predisposes affected offspring to depressive-like behavior. These results are the first to demonstrate that relatively low levels of arsenic exposure during development can have long-lasting adverse effects on behavior and neurobiological markers associated with these behavioral changes.
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States.
Ebany J
EJ
Martinez
Bethany L
BL
Kolb
Angela
A
Bell
Daniel D
DD
Savage
Andrea M
AM
Allan
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001151:Arsenic / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D003863:Depression / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006380:Helplessness, Learned; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011485:Protein Binding / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D013550:Swimming; D014280:Triglycerides / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D014280:Triglycerides; D014316:Tritium; D044282:Receptor, Serotonin, 5-HT1A; D005680:gamma-Aminobutyric Acid; D000099052:CRF Receptor, Type 1; C057077:1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol; D001151:Arsenic; D003345:Corticosterone