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CEREBELLAR PARAMETERS IN DEVELOPING 15 DAY OLD RAT PUPS TREATED WITH PROPYLTHIOIJRACIL IN COMPARISON WITH 5 AND 24 DAY OLD
Abstract
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 hgpothyrovinemia 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 n~lmber of glial cells in treated pups compared with control was
observed. There was signilicant decrease (P<0.05) in the mean neuronlneuroglia 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 granulefful-kinje cells in the treated group
compared with control. The linear regression compariscm 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.
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 hgpothyrovinemia 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 n~lmber of glial cells in treated pups compared with control was
observed. There was signilicant decrease (P<0.05) in the mean neuronlneuroglia 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 granulefful-kinje cells in the treated group
compared with control. The linear regression compariscm 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.
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