To immunohistochemically localize Bax proteins in pyramidal cells of cerebral cortex in hypothyroid neonates and to observe the effect of melatonin on these cells.

In the current study, we reported the beneficial effects of melatonin in preventing neonatal neuronal apoptosis induced by maternal hypothyroidism. During the gestation and early lactation stages, the mother rats were given propylthiouracil (PTU) to inhibit their thyroid gland activity which resulted in the increased serum TSH and reduced T4 levels. This maternal hypothyroidism caused neuronal apoptosis of their pups, particularly in the CA3 area of hippocampus. Melatonin administration preserved function of thyroid gland and significantly reduced the apoptosis. Further studies have uncovered the potentially protective mechanisms of melatonin, that is, as a mitochondrial targeted antioxidant, melatonin preserves the mitochondrial outer membrane, inhibits the release of cytochrome C from mitochondria to cytoplasm and down regulates the gene expressions of Bax, along with caspases 3 and 9. Thus, melatonin breaks the mitochondria related apoptotic pathway to suppress the neuronal apoptosis induced by the maternal hypothyroidism.  Considering the limited remedies to effectively treat hypothyroidism associated neonatal brain damage, melatonin may provide an alternative method for this disorder.

No abstract