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Adult neural stem cell cycling in vivo requires thyroid hormone and its alpha receptor
Author(s) -
Lemkine G. F.,
Raji A.,
Alfama G.,
Turque N.,
Hassani Z.,
Alegria-Prévot O.,
Samarut J.,
Levi G.,
Demeneix B. A.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2916fje
Subject(s) - neurogenesis , subventricular zone , neural stem cell , biology , thyroid hormone receptor , neuroblast , stem cell , microbiology and biotechnology , progenitor cell , endocrinology , thyroid
ABSTRACT Thyroid hormones (TH) are essential for brain development. However, information on if and how this key endocrine factor affects adult neurogenesis is fragmentary. We thus investigated the effects of TH on proliferation and apoptosis of stem cells in the subventricular zone (SVZ), as well as on migration of transgene‐tagged neuroblasts out of the stem cell niche. Hypothyroidism significantly reduced all three of these processes, inhibiting generation of new cells. To determine the mechanisms relaying TH action in the SVZ, we analyzed which receptor was implicated and whether the effects were played out directly at the level of the stem cell population. The α TH receptor (TRα), but not TRβ, was found to be expressed in nestin positive progenitor cells of the SVZ. Further, use of TRα mutant mice showed TRα to be required to maintain full proliferative activity. Finally, a direct TH transcriptional effect, not mediated through other cell populations, was revealed by targeted gene transfer to stem cells in vivo. Indeed, TH directly modulated transcription from the c‐myc promoter reporter construct containing a functional TH response element containing TRE but not from a mutated TRE sequence. We conclude that liganded‐TRα is critical for neurogenesis in the adult mammalian brain.