Hypothyroidism alters the development of radial glial cells in the term fetal and postnatal neocortex of the rat.
Alterations of thyroid function during human development are known to produce extensive damage to the central nervous system including severe mental retardation. Using immunohistochemistry to identify the intermediate filament nestin, we have studied the possible influence of fetal and neonatal hypothyroidism on neocortical neuronal migration by arresting the normal development of the radial glial scaffold. By embryonic day 21 (E21), hypothyroid animals had a significant decrease in the number of nestin immunoreactive processes in the presumptive visual cortex. By postnatal day 5 (P5), hypothyroid animals showed a significant increase in the number of glial processes in relation with controls, although only in the upper layers of the visual cortex. Moreover, by P10, there was a marked increase in the number of radial glial processes in hypothyroid animals in superficial and deep zones of the visual cortex with respect to control animals. Our data indicate an important delay in the formation of the radial glial scaffold during the embryonic stage in hypothyroid animals that was interestingly accompanied by the later presence of abundant nestin immunoreactive fibers at P10. This impairment in the evolution of radial glia during development might be affecting the normal neuronal migratory pattern in the neocortex of hypothyroid rats.
Facultad de Medicina and Centro Regional de Investigación Biomédica, Universidad de Castilla-La Mancha, Avenida de Almansa s/n, 02071 Albacete, Spain. JuanRamon.Martinez@ulcm.es
Juan Ramon
JR
Martinez-Galan
Francisco
F
Escobar del Rey
Gabriela
G
Morreale de Escobar
Maria
M
Santacana
Antonio
A
Ruiz-Marcos
D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000494:pharmacology; D002465:Cell Movement; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D007037:Hypothyroidism / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D019579:Neocortex / Q000196:embryology* / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000502:physiology*; D011247:Pregnancy; D051381:Rats
D013956:Antithyroid Agents; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D008713:Methimazole