Effect of maternal thyroxine treatment on the offspring's brain development with fetal alcohol effects in the rats / 소아과

PURPOSE: This study aimed to investigate whether exogenous thyroxine(T4) treatment to alcohol-fed dams would ameliorate the detrimental effects of alcohol on the postnatal development of neuropeptide-Y(NPY)-containing neurons of the cerebral cortex and hippocampus of the offspring. METHODS: Time-pregnant rats were divided into three groups. An alcohol-fed group A received 35 calories of liquid alcohol diet daily from gestation day 6; control group B was fed a liquid diet in which dextrin replaced alcohol isocalorically; and alcohol+T4 group C received 35 calories of liquid alcohol diet and exogenous thyroxine subcutaneously. The features of the growth and maturation of rat brain tissue were observed at 0, 7, 14, 21 and 28 postnatal days via immunohistochemistry. RESULTS: Group C showed prominent NPY immunoreactivity in the cerebral cortex compared to group A and B at P7. In group C, NPY-containing neurons were widely distributed in the all layers of cerebral cortex after P14. Also, numerical decreases of NPY-containing neuron were not found according to increasing age in group C. A decrease of NPY-containing neurons, however, was clearly observed in group A compared to group C at P28. In the hippocampus, similar patterns appeared in groups B and C after P7. Especially, in groups B and C, NPY-containing fibers formed plexus in the cerebral cortex and hippocampus at P14. CONCLUSION: These results suggest that the increase of NPY synthesis caused by maternal administration of exogenous thyroxine may convalesce fetal alcohol effects, one of the effects of the dysthyroid state following maternal alcohol abuse.

Effect of Exogenous Thyroxine on the Postnatal Development of Serotonin-containing Neuron in Fetal Alcohol Effects in the Rat Raphe Nuclei / 체질인류학회지

Serotonin (5-hydroxytryptamine, 5-HT) has been concerned in the pathophysiology of various neuropsychiatric disorders. It is known to modulate emotion, cognition, endocrine activity, motor function, and pain. In the present study, the effects of exogenous thyroxine (T4) on the postnatal development of serotonin-containing neuron in the rat raphe nuclei with fetal alcohol effects were investigated using immunohistochemistry. These experimental animals were divided into three groups : the alcohol-fed group received 35 calories liquid ethanol diet; the control pair-fed group was fed a liquid diet in dextrin replaced alcohol isocalorically; alcohol+T4 group received alcohol diet and exogenous thyroxine subcutaneously. After the pups were born, the pups of each were fostered by surragate mother. An average of four pups, one from each litter, were killed at days 0, 7, 14, 21, and 28 for each of the above three groups. As a result, in alcohol group, serotonin-immunoreactivity was weakly stained at all postnatal ages compared to control pair-fed and alcohol+T4 group. The intensity of serotonin immunoreactivity was more prominent in alcohlol+T4 group than in control pair-fed group at P0. Mature patterns of serotonin-containing neurons were observed in control pair-fed and alcohol+T4 group at P7. A similar developmental pattern of serotonin-containing neuron was observed on and after P7 in control pair-fed and alcohol+T4 group. These results suggest that the increase of serotonin synthesis during early postnatal life caused by maternal administration of exogenous thyroxine may ameliorate fetal alcohol effects, one of the ill effects as a result of the dysthyroid state following maternal alcohol abuse.

Effect of Maternal Thyroxine Treatment on the Postnatal Development of Brain-derived Neurotrophic Factor-containing Purkinje Cell in Fetal Alcohol Effects in the Rat Cerebellum / 체질인류학회지

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 with malnutrition. Especially, continuous alcohol consumption during critical period of brain development is very likely to produce fetal alcohol effects. The aims of this study are to investigate whether exogenous thyroxine treatment to alcohol -fed dams may ameliorate the detrimental effects of alcohol on the postnatal development of BDNF -containing Purkinje cell of the cerebellar cortex of the offspring. The morphological features of the growth and maturation were observed at 0, 7, 14, 21, 28 postnatal days via immunohistochemistry. In addition, electron microscopic finding of BDNF -containing Purkinje cell at P14 was also examined. Time -pregnant rats were divided into three groups. Alcohol -fed group received 35 calories of liquid alcohol diet daily from gestation day 6; control pair -fed group was fed a liquid diet in which dextrin replaced alcohol isocalorically; alcohol +/-T4 group received 35 calories liquid alcohol diet and exogenous thyroxine subcutaneously. As a result, a similar developmental pattern of BDNF -immunoreactive Purkinje cells was observed in control pair - fed and alcohol+/-T4 group on and after P14. These cells of alcohol -fed group showed immature features. Single -layer arrangement of these cells in alcohol -fed group was not completely achieved throughout postnatal life. Electron microscopic observations of BDNF -immunoreactive Purkinje cells at P14 revealed large nucleus, small cytoplasm, small amount of ribosomal collection and rudimentary cytoplasmic organelles in alcohol -fed group. The morphology of BDNF -immunoreactive Purkinje cell in alcohol +/-T4 group was similar to that in control pair -fed group. It was characterized by numerous short segments of rough endoplasmic reticulum, many of which showed a tendency of parallel alignment that suggested an attempt at Nissl body configuration. The cytology of Golgi complexes was also found within the cytoplasm in perinuclear location. Those observed differences of postnatal maturation patterns between alcohol -fed and alcohol +/-T4 group may indicate the beneficial effects on the postnatal development of BDNF -containing Purkinje cells in cerebellar cortex in the pups of thyroxine -treated alcohol -exposed dams. These results suggest that the increase of BDNF synthesis during early postnatal life caused by maternal administration of exogenous thyroxine may ameliorate fetal alcohol effects as a result of the dysthyroid state following maternal alcohol abuse.