Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In\r\ncontrast to 3,3??,5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive\r\nmetabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a\r\nfactor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the\r\ncellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that\r\nhippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience\r\nto stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover\r\nin these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1500 mcg/kg but not 250mcg/kg in\r\nnaive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This\r\ndemonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests\r\nimportant central functions of T2, whose biological role only lately is becoming to be elucidated.
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