Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Locomotor deficiencies and aberrant development of subtype-specific GABAergic interneurons caused by an unliganded thyroid hormone receptor α1. / Wallis, Karin; Sjögren, Maria; Van Hogerlinden, Max; Silberberg, Gilad; Fisahn, André; Nordström, Kristina; Larsson, Lars; Westerblad, Håkan; De Escobar, Gabriela Morreale; Shupliakov, Oleg; Vennström, Björn.
в: Journal of Neuroscience, Том 28, № 8, 20.02.2008, стр. 1904-1915.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Locomotor deficiencies and aberrant development of subtype-specific GABAergic interneurons caused by an unliganded thyroid hormone receptor α1
AU - Wallis, Karin
AU - Sjögren, Maria
AU - Van Hogerlinden, Max
AU - Silberberg, Gilad
AU - Fisahn, André
AU - Nordström, Kristina
AU - Larsson, Lars
AU - Westerblad, Håkan
AU - De Escobar, Gabriela Morreale
AU - Shupliakov, Oleg
AU - Vennström, Björn
PY - 2008/2/20
Y1 - 2008/2/20
N2 - Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor α1 (TRα1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TRα1 as the receptor isoform mediating these effects.
AB - Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor α1 (TRα1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TRα1 as the receptor isoform mediating these effects.
KW - Calretinin
KW - GABA
KW - Hypothyroid
KW - Interneuron
KW - Locomotion
KW - Parvalbumin
KW - Thyroid hormone receptor
UR - http://www.scopus.com/inward/record.url?scp=39749171735&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5163-07.2008
DO - 10.1523/JNEUROSCI.5163-07.2008
M3 - Article
C2 - 18287507
AN - SCOPUS:39749171735
VL - 28
SP - 1904
EP - 1915
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 8
ER -
ID: 40831703