Thyroid hormone receptor isoforms are sequentially expressed in oligodendrocyte lineage cells during rat cerebral development
✍ Scribed by Jean-Luc Carré; Corinne Demerens; Angeles Rodríguez-Peña; Hervé H. Floch; Guy Vincendon; Louis L. Sarliève
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 259 KB
- Volume
- 54
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
In the mammalian brain, thyroid hormones regulate myelination. Their actions are mediated by interactions with nuclear receptors that function as ligandregulated transcription factors. Two genes, ␣ and , encode different isoforms, of which only the  and ␣1 isoforms are authentic nuclear triiodothyronine (T3)receptors (NT3R). In agreement with the important role of T3 on myelination and oligodendrocyte generation, the presence of NT3Rs has been reported in oligodendrocytes and their precursors. We and others have shown that both progenitors and oligodendrocytes in vitro express the ␣1 and ␣2 isoforms, but the expression of the 1 isoform is confined to differentiated oligodendrocytes, suggesting that they have different functions. To establish if this is the case during development in vivo, we have studied NT3R isoform expression in glial cells isolated by density gradient centrifugation from rat brains of various ages. We report the presence of the ␣1 NT3R and its variant ␣2, but not that of the 1 isoform, in newborn rat glial progenitors. The pattern of expression of 1, both at the level of mRNA and protein, parallels the increase in the number of oligodendrocytes. We found a significant change in the kinetic parameters of [ 125 I]-T3 binding to NT3Rs in these cells during the first month of life, consisting of an increase in the binding capacity that peaks with myelination, and a significative decrease in Kd that coincides with the switch from the ␣ to the 1 isoform. Thus, the expression of NT3R isoforms in the rat oligodendrocyte lineage changes radically from the ␣ to the 1 isoform during the period when oligodendrocytes differentiate from progenitors.