Title: Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism.
Authors: Tyler, Christina R; Solomon, Benjamin R; Ulibarri, Adam L; Allan, Andrea M
Published In Neurotoxicology, (2014 Sep)
Abstract: Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism.
PubMed ID: 24952232
MeSH Terms: Animals; Antidepressive Agents, Second-Generation/therapeutic use*; Arsenic/toxicity*; Depression/chemically induced*; Depression/drug therapy*; Female; Fluoxetine/administration & dosage; Fluoxetine/therapeutic use*; Helplessness, Learned; Hippocampus/drug effects; Hippocampus/metabolism; Hippocampus/physiology; Male; Mice; Mice, Inbred C57BL; Motor Activity/drug effects; Neurogenesis/drug effects; Pregnancy; Prenatal Exposure Delayed Effects; Serotonin Uptake Inhibitors/therapeutic use*; Stress, Psychological/drug therapy