Regulation of the L1 cell adhesion molecule by thyroid hormone in the developing brain.
Thyroid hormone is essential for brain maturation, regulating neuronal differentiation and migration, myelination, and synaptogenesis. Mutations in the cell adhesion molecule L1 cause severe neurological abnormalities in humans. We studied the effect of thyroid hormone deprivation and administration on L1 expression. Northern and in situ hybridization studies showed that hypothyroidism induces a marked increase in L1 mRNA levels in the caudate putamen, cerebral cortex, amygdala, and some thalamic nuclei. L1 protein was overexpressed in embryonic and newborn hypothyroid rats in the caudate putamen, internal capsule, habenula, and neocortex. Later in development, an abnormally high L1 expression was found in the cortical and cerebellar white matter, corpus callosum, anterior commissure, thalamocortical projections, and striatal fiber tracts of hypothyroid animals. Thyroid hormone administration reversed the upregulation of L1 expression in vivo and in cultured cells. Thus, alterations of L1 expression may contribute to the profound abnormalities caused by hypothyroidism in the developing brain.
Alvarez-Dolado
M
M
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Spain.
Cuadrado
A
A
Navarro-Yubero
C
C
Sonderegger
P
P
Furley
A J
AJ
Bernal
J
J
Muñoz
A
A
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007037:Hypothyroidism / Q000503:physiopathology*; D017403:In Situ Hybridization; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D014284:Triiodothyronine; D013974:Thyroxine