Gestational Hypoxia Induces Sex-Differential Methylation of Crhr1 Linked to Anxiety-like Behavior

Autor: Fan-Sen Meng, Ji-Zeng Du, Xi Wang, Zong-Yun Liu, Xue-Qun Chen, Ke Hao, Jun-Ming Fan
Rok vydání: 2013
Předmět:
DNA (Cytosine-5-)-Methyltransferase 1
Male
endocrine system
medicine.medical_specialty
Corticotropin-Releasing Hormone
Offspring
DNA Mutational Analysis
Neuroscience (miscellaneous)
Anxiety
Biology
Receptors
Corticotropin-Releasing Hormone
Corticotropin-releasing hormone receptor 1
Rats
Sprague-Dawley
Cellular and Molecular Neuroscience
Pregnancy
Internal medicine
medicine
Animals
DNA (Cytosine-5-)-Methyltransferases
RNA
Messenger
Hypoxia
Luciferases
Promoter Regions
Genetic
Demethylation
Sex Characteristics
Behavior
Animal
Gene Expression Regulation
Developmental
Intermittent hypoxia
DNA Methylation
Amygdala
Embryo
Mammalian
Rats
DNA demethylation
Endocrinology
nervous system
Neurology
CpG site
Hypothalamus
DNA methylation
CpG Islands
Female
hormones
hormone substitutes
and hormone antagonists
Paraventricular Hypothalamic Nucleus
Zdroj: Molecular Neurobiology. 48:544-555
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-013-8444-4
Popis: Stress during gestation increases vulnerability to disease and changes behavior in offspring. We previously reported that hypoxia and restraint during pregnancy sensitized the hypothalamic-pituitary-adrenal (HPA) axis and induced anxiety-like behavior in the adult offspring. Here, we report that gestational intermittent hypoxia (GIH) elicited a sex-dependent anxiety-like behavior in male P90 offspring and activation of corticotropin-releasing hormone (CRH) and CRH type-1 receptor (CRHR1) mRNA in the hypothalamic paraventricular nucleus (PVN) and in male E19 hypothalamus. These linked to demethylation at several specific sites of CpG island of Crhr1 promoter in P90 PVN and E19 embryo hypothalamus in GIH groups. Crhr1 DNA demethylation is more crucial in CpG island 1 than island 2 for activation of CRHR1 mRNA. DNMT3b is required for the Crhr1 DNA methylation than DNMT1 and DNMT3a in increased CRHR1 mRNA. We first address a novel hypothesis that GIH-induced male-sex-dependent demethylation at CpG sites of Crhr1 DNA in promoter triggers elevation of CRHR1 mRNA in PVN and anxiety-like behavior in adult offspring.
Databáze: OpenAIRE
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