Stereological analysis of the cerebellum of 24-day old rats with propylthiouracil-induced hypothyroidism

Objective: To investigate the structural parameters of the developing cereb ellum in propylthiouracil (PTU)-induced hypothyroidism during pre and postn atal stages in 24 day old rat pups. Method: Hypothyroidism was induced by feeding the breeding dams with BTU in water before and during copulation, pregnancy and lactation and the pups t hrough the dams and ingestion in water. The number of control and treated d ams and pups was five for each dam group and twelve and thirteen for pups r espectively. The whole cerebellum was dissected out from the pups and proce ssed routinely for histological examination and morphometric analysis. The total volumes of cerebellum, intracerebellar nuclei and cerebellar compartm ents were estimated by Cavalieri method. The mean numerical densities of ne urones and neuroglia in the intracerebellar nuclei and Purkinje, granule an d combined stellate and basket cells in cerebellar cortex were estimated us ing optical disector and the total numbers calculated as the product of the respective numerical densities and reference volumes. Results: The treated dams and pups Rad relatively lower mean body weights a nd etraiodothyronine (T-4) serum concentrations. The serum Triiodothyronine (T-3) was normal and lower in the treated dams and pups respectively. The differences in the respective body weights and dam T-4 concentration in tre ated dams and pups were significant (p<0.05) compared to the control. Morph ometric results showed that the mean volumes of cerebellum, intracerebellar nuclei, white matter, internal granular layer, molecular layer and the cer ebellar cortex were lower and the differences between the values for each p arameter were significant (p<0.05) in the treated pups compared to the cont rol. The mean numerical densities of neurones and neuroglia in the intracer ebellar nuclei (Nvne; Nvgl) and the combined stellate and basket cells (Nvs b) in the cerebellar cortex were relatively higher and the mean values for the respective numerical densitys of Purkinje and granule cells (Nvpu; Nvgr ) were relatively lower in the treated pups compared to the control. On the other hand the treated pups had relatively lower values for the respective total numbers of neurons (Nne), neuroglia (Ngl), Purkinje (Npu), granule ( Ngr) and the combined stellate and basket (Nsb) cells compared to the contr ol. The differences between the respective values for Nvne, Nvsb, Npu,and N gs, were significant (p<0.05). Conclusion: These results show that rat pups with PTU-induced hypothyroidis m have relatively Bower mean values for the structural parameters in the ce rebellum when compared to control pups, This confirms that growth and matur ation of the cerebellum is dependent on the maintenance of normal T-4 and T -3 Bevels, underscores the magnitude of the deviations from the normal and sheds light on possible structural limitations in the cerebellum in cretins .