title: Hippocampal gene expression of deiodinases 2 and 3 and effects of 3,5-diiodo-L-thyronine T2 in mouse depression paradigms.
abstract: Central thyroid hormone signaling is important in brain function/dysfunction, including affective disorders and depression. In contrast to 3,3',5-triiodo-L-thyronine (T3), the role of 3,5-diiodo-L-thyronine (T2), which until recently was considered an inactive metabolite of T3, has not been studied in these pathologies. However, both T3 and T2 stimulate mitochondrial respiration, a factor counteracting the pathogenesis of depressive disorder, but the cellular origins in the CNS, mechanisms, and kinetics of the cellular action for these two hormones are distinct and independent of each other. Here, Illumina and RT PCR assays showed that hippocampal gene expression of deiodinases 2 and 3, enzymes involved in thyroid hormone regulation, is increased in resilience to stress-induced depressive syndrome and after antidepressant treatment in mice that might suggest elevated T2 and T3 turnover in these phenotypes. In a separate experiment, bolus administration of T2 at the doses 750 and 1,500 mcg/kg but not 250 mcg/kg in naive mice reduced immobility in a two-day tail suspension test in various settings without changing locomotion or anxiety. This demonstrates an antidepressant-like effect of T2 that could be exploited clinically. In a wider context, the current study suggests important central functions of T2, whose biological role only lately is becoming to be elucidated.
authors.affiliation: Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnii proesd 1, Chernogolovka, Moscow Region 142432, Russia.
authors.forename: Natalyia
authors.initials: N
authors.lastname: Markova
authors.affiliation: Timantti AB, Sundbyberg 104, 174 07 Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Chernopiatko
authors.affiliation: Department of Preventive Medicine, Maastricht Medical Center in Annadal, Becanusstraat 17 A0, 6216 BX Maastricht, The Netherlands.
authors.forename: Careen A
authors.initials: CA
authors.lastname: Schroeter
authors.affiliation: Carbone Cancer Center, University of Wisconsin, WIMR 3016, 1111 Highland Avenue, Madison, WI 53705, USA ; Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaia 8, Moscow 125315, Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Malin
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaia 8, Moscow 125315, Russia.
authors.forename: Aslan
authors.initials: A
authors.lastname: Kubatiev
authors.affiliation: Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnii proesd 1, Chernogolovka, Moscow Region 142432, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Bachurin
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229 ER Maastricht, The Netherlands ; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Rua da Junqueira 96, 1349-008 Lisbon, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Costa-Nunes
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229 ER Maastricht, The Netherlands.
authors.forename: Harry M W
authors.initials: HM
authors.lastname: Steinbusch
authors.affiliation: Department of Preventive Medicine, Maastricht Medical Center in Annadal, Becanusstraat 17 A0, 6216 BX Maastricht, The Netherlands ; Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229 ER Maastricht, The Netherlands ; Institute for Hygiene and Tropical Medicine, New University of Lisbon, Rua da Junqueira 96, 1349-008 Lisbon, Portugal.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Strekalova
mesh_terms: D000818:Animals; D003866:Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D004104:Diiodothyronines / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007453:Iodide Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014284:Triiodothyronine / Q000235:genetics / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D004104:Diiodothyronines; D007453:Iodide Peroxidase; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C030103:3,5-diiodothyronine; C117274:iodothyronine deiodinase type III