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Low‐Dose Thyroxine Attenuates Autism‐Associated Adverse Effects of Fetal Alcohol in Male Offspring's Social Behavior and Hippocampal Gene Expression
Author(s) -
TuncOzcan Elif,
Ullmann Timothy M.,
Shukla Pradeep K.,
Redei Eva E.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12183
Subject(s) - psychology , autism , psychiatry , offspring , pregnancy , genetics , biology
Background Fetal alcohol spectrum disorder ( FASD ) is characterized by neurodevelopmental anomalies manifesting in cognitive and behavioral deficits in the offspring with diverse severities. Social behavior is affected in FASD , and these deficits overlap with those of autism spectrum disorder ( ASD ). Identifying some of the molecular characteristics related to ASD in an animal model of FASD could ultimately provide details on the underlying molecular mechanisms of both disorders that could lead to novel treatments. Methods Pregnant S prague– D awley rats received the following diets: control ( C ; ad libitum standard laboratory chow), nutritional control pair‐fed ( PF ), ethanol ( E t OH ), or an E t OH diet supplemented with 0.3, 1.5, or 7.5 mg thyroxine ( T 4)/l in the diet. Social behavior and memory were tested in the adult offspring. Plasma total T 4, free T 3 (fT3), and thyroid‐stimulating hormone (TSH) levels were measured. Hippocampal expression of Gabrb3 , Ube3a , Nr2b , Rasgrf1 , and Dio3 were measured by RT ‐q PCR and protein levels of M ecp2 and S lc25a12 by W estern blotting. Results Adult male offspring of E t OH dams showed elevated f T 3 and low TSH levels. Adult male, but not female, offspring of E t OH dams exhibited social behavior and memory deficits. Expression of autism candidates, Gabrb3 , Ube3a , M ecp2, and S lc25a12, was significantly increased in the hippocampus of male offspring of E t OH dams. Hippocampal Nr2b and Dio3 were also increased, while Rasgrf1 was decreased in the same population. Peripheral thyroid function, social behavioral deficits, and altered expression of the above genes were normalized by simultaneous administration of 0.3 mg/l T 4 in the E t OH diet. Conclusions Our data suggest that social interaction deficits of FASD share molecular mechanism with ASD by showing altered hippocampal expression of several ASD candidate genes. Social interaction deficits as well as the gene expression changes in the offspring of E t OH ‐consuming dams can be reversed by low dose of thyroid hormone supplementation to the mothers.