title: DNA Methylation of the EphA5 Promoter Is Associated with Rat Congenital Hypothyroidism.
abstract: Thyroid hormones (THs) are essential for normal development of the mammalian central nervous system through regulation of TH-responsive genes. EphA5, an important TH-responsive gene encoding the tyrosine kinase receptor EphA5, regulates synaptogenesis initiation and synaptic remodeling during brain development. Abnormal EphA5 expression is involved in the development of congenital hypothyroidism (CH). To show the regulatory mechanism of EphA5 expression in CH rats, we analyzed the correlation between methylation of the EphA5 promoter and its expression in the hypothyroid hippocampus and hippocampal neurons. Demethylation treatment using 5'-azadeoxycytidine upregulated EphA5 expression and rescued the effects of hypermethylation, suggesting a novel regulatory mechanism of EphA5 expression in CH rats. Our results suggest a potentially new approach for the development of drugs to restore neurocognitive impairments associated with CH.
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
authors.forename: Honghua
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
authors.forename: Baolan
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong, 226001, Jiangsu Province, China. kevinliu2013@yahoo.com.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D000077209:Decitabine; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D036123:Receptor, EphA5 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000077209:Decitabine; D036123:Receptor, EphA5; D001374:Azacitidine
keywords: Congenital hypothyroidism; EphA5; Hippocampus; Methylation; Neuron