Maternal alcohol abuse is one of the most prominent causes of mental retardation among children in China.Thyroid hormones exert an important role in the development of the central nervous system.This study investigated whether exogenous thyroxine treatment to offspring of fetal alcohol effects may mitigate the detrimental effects of alcohol on the postnatal development of brain-derived neurotrophic factor-immunoreactive Purkinje cells in the cerebellar cortex.Timed-pregnant rats on the 6th day of gestation were divided into six groups: control,alcohol,alcohol + low-dose thyroxine,alcohol + medium-dose thyroxine,alcohol + high-dose thyroxine,and surrogate.Rats in the alcohol,alcohol + low-dose thyroxine,alcohol + medium-dose thyroxine,alcohol + high-dose thyroxine groups received 35 calories of liquid alcohol in their diet daily.The control group rats were fed with a liquid diet in which equal calories of milk (containing 8% sugar) replaced the alcohol.The surrogate group rats were fed normally.Within 6 hours after birth of the last pup,the pups of all groups except the surrogate group were fostered by the surrogate group mothers,and the pups in groups receiving thyroxine received exogenous thyroxine (2.5,5,and 7.5 ug/kg Per day) subcutaneously.The growth and maturation features of rat cerebellar cortex tissue were observed at 0,7,14,21,28,and 60 postnatal days by immunohistochemistry.The results suggested that the blood alcohol concentration was significantly higher in the alcohol and alcohol + low-dose thyroxine groups than in the control group.Thyroxine concentration was significantly decreased in the alcohol group dams compared with the control group.A similar developmental pattern of brain-derived neurotrophic factor-immunoreactive Purkinje cells was observed on and after postnatal day 14 in the control,alcohol + medium-dose thyroxine,and alcohol + high-dose thyroxine groups.In contrast,the Purkinje cells of the alcohol and alcohol + low-dose thyroxine groups showed immature features.The characteristic single-layer arrangement of these Purkinje cells in the alcohol group was never completely achieved throughout postnatal life.In addition,the number of Purkinje cells in the alcohol group were decreased at postnatal day 28 day compared with those in the control and alcohol + thyroxine groups.When dams were exposed to alcohol during gestation,not only was their blood thyroxine concentration significantly decreased,but synthesis of brain-derived neurotrophic factor in the cerebellar cortex and growth of brain-derived neurotrophic factor-immunoreactive Purkinje cells were impaired in the offspring.Exogenous thyroxine treatment may ameliorate these effects of fetal alcohol because of the dysthyroid state induced by maternal alcohol abuse.