title: Hypoxic preconditioning increases triiodothyronine (T3) level in the developing rat brain.
abstract: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the major causes of neurodegeneration and mortality in the neonatal period. Although hypoxic preconditioning (HPC) provided strong neuroprotection against HIE in an animal model, the mechanism underlying this effect is not fully understood especially in the immature brain. Here, we investigated whether thyroid hormones (THs), especially triiodothyronine (T3), which are essential during normal brain development, contribute to the neuroprotective mechanisms of HPC by using an established model of HPC in neonatal rats. HPC treatment (8% O2 for 2.5h at 37°C) was performed in immature rats at postnatal day 6 (P6). Subsequently, we investigated the levels of THs, TH receptors (TRs) and type 2 and 3 deiodinase (D2 and D3) mRNA, and glutamate transporter 1 (GLT1) at 24h after HPC treatment, and myelin basic protein (MBP) at 6, 12 and 24h after HPC treatment. The HIE procedure was performed at 24h after HPC, and the neuroprotective effect of HPC was assessed via microtubule-associated protein 2 (MAP2) and MBP immunohistochemical staining at 14 days after HIE (P21). HPC treatment afforded marked neuroprotection at 14 days after HIE. The local level of T3 was upregulated 24h after HPC treatment in the developing rat brain, probably via the upregulation of D2. In addition, the expression of MBP and GLT1, which are the downstream protein of T3, were significantly increased 24h after HPC treatment. The present study indicates that thyroid hormones and their associated molecules may be involved in neuroprotective mechanisms of HPC during the developmental period.
authors: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kenji
authors: K
authors: Minato
authors: Takuji
authors: T
authors: Tomimatsu
authors: Kazuya
authors: K
authors: Mimura
authors: Otgonbaatar
authors: O
authors: Jugder
authors: Aiko
authors: A
authors: Kakigano
authors: Tomoko
authors: T
authors: Kanayama
authors: Satoko
authors: S
authors: Fujita
authors: Yukiko
authors: Y
authors: Taniguchi
authors: Takeshi
authors: T
authors: Kanagawa
authors: Masayuki
authors: M
authors: Endo
authors: Tadashi
authors: T
authors: Kimura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D013974:Thyroxine