1. ¹Laboratoire de Pharmacologie, Université René Descartes, Paris, France
2. ²U488 Inserm, Le Kremlin-Bicêtre cedex, France

Correspondence: Dr F Courtin, U488 Inserm, 80 rue du Gl Leclerc, 94276 Le Kremlin-Bicêtre cedex, France. E-mail: courtin@kb.inserm.fr

³These two authors contributed equally to this work.

⁴Current address: INSERM E 00-18, Laboratoire de Biochimie et Biologie Moléculaire, 4 rue Larrey, 49033 Angers, France.

⁵Current address: School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Manchester M13-9PT, UK.

⁶Current address: Sirbu Building, Division of Neurosciences, Beckman Research Institute and City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.

Received 15 June 2004; Revised 30 September 2004; Accepted 21 October 2004; Published online 26 January 2005.

Abstract

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.