Thyroxine treatment and recovery of hypothyroidism-induced pyramidal cell damage

We have previously shown that changes occur in pyramids of area 17 of the rat visual cortex both after thyroidectomy (T) at 10 and at 40 days of age. To assess the effects of thyroxine treatment, instituted at different ages after T, two series of experiments were performed. A : rats were T at 10 days of age and either left untreated, or injected once daily with 1.5 micrograms thyroxine (T4)/100 g body weight. Treatment was started at 12, 15, 20, 30 or 40 days of age. Groups of untreated and T4-treated T rats and of age-paired intact controls were killed at different ages, ranging from 40 to 80 days. B : rats were T at 40 days of age, a group being treated with the same T4 dose starting 30 days after T. These animals, solvent-treated T rats and intact age-paired controls were killed at 90 days of age. The number and distribution of spines along the shaft of Golgi-stained pyramidal cells of the visual cortex were measured and fitted by a mathematical model developed previously. Body weights, pituitary growth hormone contents, plasma thyrotropic hormone, thyroxine and triiodothyronine levels were measured to assess the degree of hypothyroidism. It was found that treatment with T4 of rats T at 10 days of age prevented the alterations of pyramidal cells, provided treatment was started by 12 days of age and euthyroidism was maintained. In rats T at 40 days of age, treatment with T4 had an ameliorating effect despite a delay in onset of treatment of 30 days after T. Whatever the mechanisms which are involved, the present results stress once more the importance of very early treatment of hypothyroid newborns, if permanent cortical brain damage is to be prevented.