Effect of propylthiouracil induced hypothyroidism in developing rat cerebellum: comparison of cerebellar parameters in five day old normal and treated rat pups

Abstract

The effect of pre and postnatal hypothyroid environment on the development of cerebellum in the rat pups was determined. Four groups of rat dams, namely control, Group I, II and III were treated with propylthiouracil (PTU) in water for different length of time during pregnancy and nursing periods. The pups born from these dam groups were subsequently named after the corresponding dam group, namely control, Group I, II and III. General quantitative results showed that pups from the treated dams had significantly lower (p < 0.05) body weights compared to control pups. Cerebella from five day old pups were taken and structural changes estimated using unbiased "design based" stereological methods, which have made it possible to investigate specific qualities in the organ. The total volumes of cerebellum and intracerebellar nuclei were estimated using Cavalieri Principle. The mean total volume of cerebellum and the mean total volume of intracerebellar nuclei were significantly lower (p < 0.05) in all the pup groups (I, II, III) from the treated dams compared to control pups from the control dams. The cerebellar volume decreased in relation to the duration of treatment. The mean ratio of the total volume of intracerebellar nuclei to volume of cerebellum was significantly increased (p < 0.05) in Group III pups compared to control and Group I pups. The mean numerical density of neurones in the intracerebellar nuclei was nearly equal in all the pup groups except in Group III pups whereby it was increased. The mean total number of neurones in Groups I and II pups was reduced, but did not reach statistical significance. The mean numerical density of neuroglia in the intracerebellar nuclei was nearly the same in all the pup groups, the mean total number of glial cells was significantly reduced (p < 0.05) in Groups I and II pups compared to control and the mean neuron/glial ratio was increased in Group III pups compared to control and other treated groups. Thus, the neuroglia appear to be more sensitive to hypothyroidism than neurons. The above results show that PTU-induced hypothyroidism causes reduction in structural parameters in developing cerebellum and confirm that growth and maturation of the foetal cerebellum is dependent on the maintenance of normal T4 and T3 levels in the pregnant dam and developing pups during pre and postnatal stages of development.