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Role of type 3 deiodinase (D3) in depression induced by social isolation

Abstract

Major depression (MO) is a neuropshychological disorder that results from interplay of genetic and environmental factors and is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. 30-40% of patients with MO are resistant to current antidepressant therapy an adjunct therapy has been searched. Euthyroid patients have been treated with T3 to improve the beneficial effect of antidepressant drugs. Thyroid hormone signaling in the brain depends on plasma T4 and T3, membrane transporters, and the expression of 02 and 03, which provides a means to localized control of thyroid hormone action. 03 is largely expressed in the brain and it could be involved in the mechanism underlying the influence of thyroid hormone in the outcome of MO treatment since inactivates T4 to rT3. Adult rats exposed to alcohol during the pre-natal period showed increased depressive behavior and offspring of alcohol-consuming dams exhibit an increase in 03 protein levels in the frontal cortex and a decrease in hippocampus. We hypothesized that an increase in 03 expression could be implicated in MO. Our hypothesis is based in previous findings that Astro 02-KO mice present anxiety and depression due to a decrease in T3 signaling in the brain. To test our hypothesis we will knockdown 03 in the brain of depressed mice using a tamoxiphen-inducible neuron-specific Cre recombinase. Specifically, Oi03flox+/+ Arc-Cre/ERT2+/+ will be isolated after weaning for 3 months to cause depression and subsequently receive injection of Tamoxifen to […] (AU)