Induction of type 2 iodothyronine deiodinase in astrocytes after transient focal cerebral ischemia in the rat.
This study investigated the expression of deiodinases of thyroid hormones in the rat brain after transient occlusion of the middle cerebral artery. The activity of type 2 deiodinase (D2), which catalyzes the deiodination of thyroxine into the more active thyroid hormone 3,5,3'-triiodothyronine, was strongly increased by cerebral ischemia at 6 and 24 hours in the striatum and at 24 hours in the cerebral cortex. The activity of type 3 deiodinase, which catalyzes the inactivation of thyroid hormones, was not affected by ischemia. In situ hybridization showed, as soon as 6 hours, an upregulation of the expression of D2 mRNA in the ipsilateral striatum, which disappeared at 24 hours. In the ipsilateral cortex, the induction of D2 mRNA started at 6 hours, was increased at 24 hours and finally declined at 72 hours. These results were confirmed by reverse transcription-PCR for D2 mRNA in the striatum and cerebral cortex. The upregulation of D2 mRNA after ischemia was mainly localized in astrocytic cell bodies. These results show that D2 is rapidly induced in astrocytes after ischemic stroke. Future work will include the exploration of the role of the upregulation of this enzyme, responsible for local 3,5,3'-triiodothyronine production as a neuroprotective mechanism in the brain.
Margaill
Isabelle
I
Laboratoire de Pharmacologie, Université René Descartes, Paris, France.
Royer
Julien
J
Lerouet
Dominique
D
Ramaugé
Martine
M
Le Goascogne
Claude
C
Li
Wen Wu
WW
Plotkine
Michel
M
Pierre
Michel
M
Courtin
Françoise
F
D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D004790:Enzyme Induction / Q000502:physiology; D017403:In Situ Hybridization; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D008297:Male; D017072:Neostriatum / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097564:Iodothyronine Deiodinase Type II
D007453:Iodide Peroxidase; D012333:RNA, Messenger; D000097564:Iodothyronine Deiodinase Type II; C117274:iodothyronine deiodinase type III