uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Locomotor deficiencies and aberrant development of subtype-specific GABAergic interneuros caused by a unlignded thyroid hormopne receptor alpha-1
Show others and affiliations
2008 (English)In: Journal of Neuroscience, ISSN 0270-6474, Vol. 28, no 8, 1904-1915 p.Article in journal (Refereed) Published
Abstract [en]

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 alpha 1 (TR alpha 1) 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 TR alpha 1 as the receptor isoform mediating these effects.

Place, publisher, year, edition, pages
2008. Vol. 28, no 8, 1904-1915 p.
Keyword [en]
thyroid hormone receptor, parvalbumin, calretinin, GABA, hypothyroid, interneuron, locomotion
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-17621DOI: 10.1523/JNEUROSCI.5163-07.2008ISI: 000253426800014OAI: oai:DiVA.org:uu-17621DiVA: diva2:45392
Available from: 2008-07-29 Created: 2008-07-29Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Larsson, Lars
By organisation
Department of Neuroscience
In the same journal
Journal of Neuroscience
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 156 hits
ReferencesLink to record
Permanent link

Direct link