Document Detail

Altered Cerebellum Development and Dopamine Distribution in a Rat Genetic Model with Congenital Hypothyroidism.
MedLine Citation:
PMID:  24460919     Owner:  NLM     Status:  Publisher    
Thyroid hormones play crucial roles in the development and functional maintenance of the central nervous system. Despite the extensive studies of the neural function of thyroid hormones, little is known about the effects of hypothyroidism on behavioural traits and the mechanisms underlying such effects. Here, we report our study of congenitally hypothyroid mutant rdw rats, revealing a novel function of thyroid hormones in the central nervous system. The rdw rats were subjected to behavioural analyses such as the rotarod test, open field test, and circadian activity measurement. To determine the cause of behavioural disorders, cerebellar morphogenesis was examined by immunohistochemical analysis, and the axonal transport of dopamine in the nigrostriatal pathway was analyzed by HPLC and Western blotting. The effects of thyroxine administration to the rdw rats were examined by behavioural analysis. The rdw rats showed severe impairment of motor coordination and balance. This could be explained by the fact that the rats showed severe retardation of cerebellar morphogenesis, which correlates with the small somata and poor dendritic arborization of Purkinje cells and retarded migration of granule cells particularly during the first two postnatal weeks. Moreover, the rdw rats showed hypoactivity, characterized by decreased circadian locomotor activity. After weaning, thyroxine administration improved the dwarfism in rdw rats but had no effect on cerebellar function. In addition, the rdw rats showed anxiety and depression intrinsically to novel surroundings. Interestingly, the rdw rats showed high levels of dopamine in the substantia nigra and low levels in the striatum, an important center for the coordination of behaviour. Furthermore, low levels of tubulin in the striatum were detected, indicating the aberrant axonal transport of dopamine in the nigrostriatal pathway owing to the reduced delivery of microtubules. These findings indicate an important function of thyroid hormones in cerebellar formation and in the regulation of axonal transport of dopamine. Moreover, rdw rats will be useful for studies of brain function and behavioural disorders in congenital hypothyroidism. This article is protected by copyright. All rights reserved.
Noriaki Shimokawa; Behnaz Yousefi; Shiori Morioka; Sayo Yamaguchi; Asuka Ohsawa; Hideka Hayashi; Anri Azuma; Hiroyuki Mizuno; Masato Kasagi; Hiroko Masuda; Hisaka Jingu; Sen-Ichi Furudate; Asahi Haijima; Yusuke Takatsuru; Toshiharu Iwasaki; Motoaki Umezu; Noriyuki Koibuchi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-26
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  -     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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