모체 Thyroxine 투여가 태아알코올효과를 가진 흰쥐 대뇌겉질 및 해마의 생후 발달에 따른 BDNF함유 신경세포와 BDNF 단백질 양에 미치는 영향

Abstract

Maternal alcohol abuse is thought to be the common cause of mental retardation. Even moderate maternal alcohol consumption may produce fetal alcohol effects with behavioral and learning difficulties, if the drinking is associated malnutrition. Especially, continuous maternal alcohol consumption during critical period of brain development may induce fetal alcohol effects . In this study, the author investigated not only the effects of maternal alcohol drinking on the postnatal changes of BDNF protein contents and patterns of BDNF-containing neuron but also the influence of maternal thyroxine treatment on the postnatal development of BDNF expression in cerebral cortex and hippocampus of pups of alcohol abused mother. Time-pregnant rats were divided into three groups. Alcohol-fed group A(n = 4) received 35 calories of liquid alcohol diet daily from gestation day 6; control pair-fed group B(n = 4) was fed a liquid diet in dextrin replaced alcohol isocalorically; alcohol + T_(4) group C(n = 4) received 35 calories liquid alcohol diet and exogenous thyroxine (5㎍/kg/day) subcutaneously. After the pups were born, the pups of each were fostered by surrogate mother. The amount of BDNF was significantly higher in the alcohol + T_(4) group as compared to the alcohol-fed group at P7, P14 and P21. Especially, alcohol + T_(4)-exposed pups showed a significant increase of BDNF amount at P7. In alcohol + T_(4) group, the amount of BDNF was higher than control pair-fed group, in addition, the decrease of BDNF amount was found in alcohol-fed group compared to control pair-fed group at all ages. Alcohol + T_(4) group showed mature pattern and numerical increase of BDNF-containing cell in cerebral cortex at P7. In hippocampus, the number and immunoreactivity of BDNF-containing cell in alcohol + T_(4) group increased at P7, and began to decrease at P14. However, in alcohol + T_(4) group, the BDNF immunoreactivity in hippocampus continued to show prominent configuration until P28. This study clearly showed the increase of the BDNF-containing neurons and BDNF amount in pups of thyroxine-supplemented alcohol-exposed dams compared to alcohol-exposed pups at P7. These results suggest that maternal thyroxine treatment may induced the early stimulatory effect of BDNF synthesis during the postnatal development of cerebral cortex and hippocampus in fetal alcohol effects.