TY - JOUR
T1 - Aberrant Maturation of Astrocytes in Thyroid Hormone Receptor α1 Knockout Mice Reveals an Interplay between Thyroid Hormone Receptor Isoforms
AU - Morte, Beatriz
AU - Manzano, Jimena
AU - Scanlan, Thomas S.
AU - Vennström, Björn
AU - Bernal, Juan
PY - 2004/3
Y1 - 2004/3
N2 - Although the effects of thyroid hormones on the development of neurons and oligodendrocytes are well documented, less is known about the hormonal effects on astrocytes. Our analyses of cerebellar slices from 2-month-old T3 receptor protein (TR)α1-deficient mice show that mature astrocytes, Golgi epithelial cells, and their Bergmann processes had strongly reduced glial fibrillary acidic protein (GFAP) and nestin immunoreactivity, in contrast to wild-type mice. Furthermore, the Bergmann processes exhibited an irregular GFAP staining. A similar expression of nestin and GFAP was observed in 11-d-old (P11) mutant pups. Surprisingly, however, hypothyroidism normalized the appearance of these markers in the P11 mutants, suggesting that liganded TRβ is detrimental to astroglial cell differentiation in the absence of TRα1. To test this hypothesis, hypothyroid mice were treated from birth until P11 with the TRβ-selective ligand GC-1. This treatment was devastating in the TRα1-/- mice, causing little if any nestin or GFAP immunoreactivity, whereas the wild-type mice were normal. The results thus indicate an important interplay between thyroid hormone receptor isoforms in astroglial cell maturation.
AB - Although the effects of thyroid hormones on the development of neurons and oligodendrocytes are well documented, less is known about the hormonal effects on astrocytes. Our analyses of cerebellar slices from 2-month-old T3 receptor protein (TR)α1-deficient mice show that mature astrocytes, Golgi epithelial cells, and their Bergmann processes had strongly reduced glial fibrillary acidic protein (GFAP) and nestin immunoreactivity, in contrast to wild-type mice. Furthermore, the Bergmann processes exhibited an irregular GFAP staining. A similar expression of nestin and GFAP was observed in 11-d-old (P11) mutant pups. Surprisingly, however, hypothyroidism normalized the appearance of these markers in the P11 mutants, suggesting that liganded TRβ is detrimental to astroglial cell differentiation in the absence of TRα1. To test this hypothesis, hypothyroid mice were treated from birth until P11 with the TRβ-selective ligand GC-1. This treatment was devastating in the TRα1-/- mice, causing little if any nestin or GFAP immunoreactivity, whereas the wild-type mice were normal. The results thus indicate an important interplay between thyroid hormone receptor isoforms in astroglial cell maturation.
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U2 - 10.1210/en.2003-1123
DO - 10.1210/en.2003-1123
M3 - Article
C2 - 14630717
AN - SCOPUS:1442323643
SN - 0013-7227
VL - 145
SP - 1386
EP - 1391
JO - Endocrinology
JF - Endocrinology
IS - 3
ER -