Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development

Barez-Lopez, Soledad; Jesus Obregon, Maria; Bernal, Juan; Guadano-Ferraz, Ana

Abstract

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis

Más información

Título según WOS: ID WOS:000431890800018 Not found in local WOS DB
Título de la Revista: CEREBRAL CORTEX
Volumen: 28
Número: 5
Editorial: OXFORD UNIV PRESS INC
Fecha de publicación: 2018
Página de inicio: 1783
Página final: 1793
DOI:

10.1093/cercor/bhx088

Notas: ISI