25/05/24, 18:07 Promoter-specific regulation of the brain-derived neurotropic factor gene by thyroid hormone in the developing rat cerebellum - …

An official website of the United States government

Here's how you know

full text links

Endocrinology. 1999 Sep;140(9):3955-61. doi: 10.1210/endo.140.9.6997.

Promoter-specific regulation of the brain-derived

neurotropic factor gene by thyroid hormone in the
developing rat cerebellum
N Koibuchi 1 , H Fukuda, W W Chin

Affiliations
PMID: 10465264 DOI: 10.1210/endo.140.9.6997

Abstract
Thyroid hormone (TH) plays a critical role in normal cerebellar development. However, the molecular
mechanisms of TH action in the developing cerebellum are not fully understood. This action could be
exerted in part through brain-derived neurotropic factor (BDNF), as cerebellar BDNF messenger RNA
(mRNA) expression is lower, and replacement of BDNF partially reverses the abnormal neurogenesis in
the hypothyroid rat. The rat BDNF gene consists of four noncoding exons (exons I-IV), each of which is
linked to a different promoter, and a protein-coding exon (exon V). To study promoter-specific
regulation of the BDNF gene by TH, ribonuclease protection assay of each exon mRNA was performed
using total developing rat cerebellar RNA. During cerebellar development, all exon mRNAs were
detected, but with different expression patterns; among noncoding exon mRNAs, exon II mRNA was
the most abundant. Daily TH replacement induced a 3-fold increase in exon II mRNA on postnatal day
(P) 15. On P30, exon II mRNA was still much greater in the TH-replaced animal. Exon I mRNA was
detected on P2 and P7. However, in contrast to exon II mRNA, TH treatment suppressed the
expression of exon I mRNA on P2. Exon III and IV mRNAs were not detected on P2 and P7, but small
amounts were observed starting on P15 in TH-replaced animals. They were not detected by P30 in
hypothyroid animals. In contrast, in the cerebral cortex, although all exons are differentially regulated
during development, the expression of each mRNA was not significantly altered by TH. These results
indicate that TH regulates BDNF gene expression in a promoter-, developmental stage-, and brain
region-specific manner, which may play an important role in region- and stage-specific regulation of
brain development by TH.

PubMed Disclaimer

Related information
MedGen
PubChem Compound (MeSH Keyword)

LinkOut - more resources

Full Text Sources
Ovid Technologies, Inc.
Silverchair Information Systems
Medical
MedlinePlus Health Information

https://pubmed.ncbi.nlm.nih.gov/10465264/ 1/1