Aberrant maturation of astrocytes in thyroid hormone receptor alpha 1 knockout mice reveals an interplay between thyroid hormone receptor isoforms.
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 T(3) receptor protein (TR)alpha1-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 TR beta is detrimental to astroglial cell differentiation in the absence of TR alpha 1. To test this hypothesis, hypothyroid mice were treated from birth until P11 with the TR beta-selective ligand GC-1. This treatment was devastating in the TR alpha 1(-/-) 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.
Morte
Beatriz
B
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas y Universidad Autónoma da Madrd, 28029 Madrid, Spain.
Manzano
Jimena
J
Scanlan
Thomas S
TS
Vennström
Björn
B
Bernal
Juan
J
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007536:Isomerism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D064231:Nestin; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta