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Cerebellar parameters in developing 15 day old rat pups treated with propylthiouracil in comparison with 5 and 24 day
1Department of Veterinary Anatomy, University of Nairobi, Kenya.
Insights
Hypothyroidism in developing rat pups significantly alters cerebellar structure, reducing neuron numbers and increasing glial cells. Maintaining thyroid hormone levels is crucial for normal cerebellar development.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- The cerebellum plays a critical role in motor control and cognitive functions.
- Thyroid hormones are essential for normal brain development, particularly during prenatal and early postnatal stages.
- Hypothyroidism during development can lead to significant structural and functional abnormalities in the brain.
Purpose of the Study:
- To investigate and quantify the structural changes in the developing cerebellum of rat pups exposed to hypothyroidism during pre- and postnatal stages.
- To compare these structural parameters in 15-day-old pups with 5-day-old and 24-day-old pups.
Main Methods:
- Propylthiouracil (PTU) was administered to dams and pups to induce hypothyroidism (hypothyroxinemia).
- Histological and stereological methods (Cavalieri Principle, disector method) were used to analyze cerebellar structure.
- Quantitative analyses included total cerebellar volume, cellular numerical densities, and cell numbers (neurons, Purkinje cells, glial cells).
Main Results:
- PTU-induced hypothyroidism led to significant reductions in cerebellar volume, internal granular layer, molecular layer, and cerebellar cortex in 15-day-old pups.
- While neuron and Purkinje cell numbers were comparable between groups, there was a significant increase in glial cells and a decrease in the neuron/neuroglia ratio.
- Significant reductions in granule cell numbers and granule/Purkinje cell ratios were observed in the treated group.
Conclusions:
- PTU-induced hypothyroidism causes significant quantitative structural variations in the developing cerebellum.
- These disruptions negatively impact progressive cellular developmental processes in the cerebellum.
- Maintaining normal thyroid hormone (T4 and T3) levels is essential for proper cerebellar growth and maturation.
Objective:
To investigate and quantify structural parameters in the developing cerebellum during hypothyroidism in pre and postnatal stages in 15 day old rat pups in comparison with 5 and 24 day old.
Methods:
Propylthiouracil (PTU) was fed to rat dams during mating, pregnancy and nursing and their pups in drinking water. Consequently hypothyroxinemia was induced in the dams and the developing foeti during prenatal period and maintained in the dams and pups. The number of treated and control dams was five in each group. The treated and control pups were eight and eleven respectively. The whole cerebellum was dissected out and routinely processed for histological and morphometric analysis. Structural changes in cerebellum were estimated using "design based" stereological methods. The total volume of cerebellum, intracerebellar nuclei and cerebellar compartments were estimated using Cavalieri Principle. Numerical density of cells was estimated using the disector method and the total cell number was then calculated.
Results:
In the 15 day pups there was significant reduction (P<0.05) in the mean volumes of cerebellum, internal granular layer, molecular layer, cerebellar cortex, mean ratio of the total volume of intracerebellar nuclei to the cerebellar volume and increased mean volume of external granular layer in treated pup group compared with control. The mean volumes of intracerebellar nuclei and white matter and the mean numerical densities and total numbers of neurons and Purkinje cells in intracerebellar nuclei and cerebellum respectively were nearly equal in control and treated groups. Significant increase (P<0.05) in the mean numerical density and total number of glial cells in treated pups compared with control was observed. There was significant decrease (P<0.05) in the mean neuron/neuroglia ratio in the intracerebellar nuclei, mean numerical density and mean total number of granule cells and reduction in the mean ratio of total number of granule/Purkinje cells in the treated group compared with control. The linear regression comparison for the total volume of the intracerebellar nuclei to total volume of the cerebellum in 5, 15 and 24 day control and treated pups and for the total number of glial cells on the total volume of intracerebellar nuclei in the same were significantly different (P<0.05). Total numbers of neurons and glial cells in the intracerebellar nuclei showed peak values in 15 day pups.
Conclusion:
Thus PTU-induced hypothyroidism causes variation in quantitative structural parameters in developing cerebellum and disrupts progressive cellular developmental processes. Maintenance of normal T4 and T3 levels during growth and maturation of cerebellum is absolutely essential.