| dc.description.abstract | ABSTRACT
The quantitative changes in the structural components of
the developing cerebellum in normal and hypothyroid rats
are riot, well known. The morphometric studies which have
been carried out on the rat cerebellum and even on other
animal species have been subject to sampling and analytical
bias. The present study was intended to provide
quantitative information on the developmental cha nqes of
the cerebellum during early postnatal life caused by
hypothyroidism using the rat as the animal model.
Propylthiouracil a drug used in treatment of thyrotoxicoses
in humans was used to induce hypothyroidism in the pregnant and nursing rat dams.
The structural changes in developing cerebellum, in
propylthiouracil induced hypothyroidism in rat dams and
pups during pre and postnatal stages were estimated in 5,
15, and 24 day old pups using unbiased "design based"
stereological methods. The total volume (V) of cerebellum,
intracerebellar nuclei and cerebellar compartments was
estimated using the Cavalieri Principle, the numerical
density of cells (Nv) using the disector method and the
total cell number (N) was calculated from the product of
cerebellar volume and numerical density.
The general experimental results showed that the treated
dams had significantly lower (P<0.05) body weights,
tetraidothyronine ('1'4) and reduced Triiodothyroniue (T3)
serum-concentrations, while the! pups had significantly
Lower (P<O. 05) body weiqhts , and decreased T4 arid T3
concentrations in serum.
Norphometric results showed that" the mean volume of
intracerebellar nuclei was reduced and significantly lower
(P<O. 05) in 5 and 24 day old PTU-P (pups treated through
the dams only) pups. The mean volume of cerebellum was
reduced in all the treated pups and was significantly lower
(P<O. 05) in all the three age groups of pups in PTU- P
groups.
Further investigation into the volume of the
compartments in 15 and 24 day old pups showed the volume of
white matter (WM) was reduced in 15 and 24 day old treated
pups. The reduction was significant (P<0.05) in 24 day old
PTU- P pups .
The mean volume of internal granular Layer (lGL),
molecular layer (t-1L) and the cortex (IGL+WM) were lower in
treated pups and significantly reduced (P<0.05) in PTU-P
pups except in PTU-injected (PTU-IN) pups where the mean
volume of IGL was hiqher than in CONTROL.
The mean ratio of the total volume of intracerebellar
nuclei La volume of cerebellum in 5 day old pups was
reduced in the PTU-10F group, significantly increased
(P~O.05) in PTU-20F and 15 day PTU-P pups, increased in 24
day the PTU-P group and reduced in the PTU-IN group.
The mean numerical density (Nv) of neurons in the
intracerebellar nuclei was reduced in 5 and 15 day old PTU-P
pups and 24 day old PTU-IN pups, but in other 5 day old
pup groups (PTU-I0F and PTU-20F which were treated for
shorter periods) and 24 day old PTU-P pups the values were
increased. This increase was significant. (P<O.05) in 24 day
old PTU-P pups.
The mean total number of neurons was reduced in all the
treated groups except PTU-20F group in 5 day old pups. The
reduction was significant (P<O.05) in PTU-IN pups.
The mean numerical density of glial cells in
intracerebellar nuclei was reduced in PTU-P and PTU-10F in
5 day old pups and PTU-P pups in 24 day old pups, while in PTU-
20F in 5 day old pups, PTU-P in 15 day old pups and PTU-IN
in 24 day old pups were increased. In 15 day old PTU-P pups
the mean nurnerical density was significantly increased
(P<O.05) .
The mean total number of glial cells was reduced in all
created groups in 5 and 24 day old pups, while in 15 day
old pups, it was significantly increased (P<O.05). The mean
total number at glial cells was significantly reduced
(P<O.05) in PTU-P and PTU-I0F pup in 5 day old groups.
The mean neuron/glia ratio in 5 day old pups was
increased in PTU-20F pups, significantly decreased (P<O.05)
in 15 day old PTU -P pups and decreased in 24 day old
treated pups.
The mean numerical density of Purkinje cells was
increased in 15 day old PTU-P pups while in 24 day old pups
it was reduced in treated groups. The mean total number of
Purkinje cells in 15 and 24 day old pups was reduced in all
treated groups. The reduction in 24 day treated puvs was
significant: (P<O.05).
The mean numerical density of granule cells was reduced
in PTU-P groups in 15 and 24 day old pups. The reduction
was significant (P<O.05) in 15 day old pups. The mean total
number of granule cells was significantly reduced (P<O.05)
in PTU-P groups in 15 and 24 day old pups. The mean total
granule cell number was increased in the PTU- IN group.
The mean numerical density of stellate and basket cell
in 24 day PTU-P pups was a significantly higher (P<O.05)
than CONTROL:The mean total stellate and basket cell
number was reduced in all treated group in 24 day old pups.
The reduction was significant: (P<O.05) in 24 day PTU-P
pups.
The mean ratio of total number at cells calculated from the
mean total numbers of granule/Purkinje (N(GR)/N (PU)), stellate
and basket/purkinje (N(SB)/N(PU)) was increased in the PTU-P
group, while granule/stellate and basket (N(GR)/N(SB)) ratio
was increased in the PTU-IN group.
Simple linear regression comparison of total volume of
intracerebellar nuclei on total volume of cerebellum showed a
significant difference (P<O.05) between the regression lines
in CONTROL and PTU-P pups. Similarly the linear regression
comparison of total number of glial cells on total volume of
intracerebellar nuclei,showed significant difference between
the regression lines in CONTROL and PTU-P pups.
The above results confirm that PTU-induced hypothyroidism
causes a reduction in structural parameters in developing
cerebellum. This investigation also confirms that growth and
maturation of the foetal cerebellum is dependent on the
maintenance of normal T4 and T3 levels and activity in the
pre and post-natal development of the cerebellum in order to
enhance normal cell proliferation, differentiation, migration
and development of the neuropil. These results underscore the
magnitude of the deviations from the normal showing that the
developmental processes in the normal and treated pups,
significantly deviate from each other. These observations shed
light on possible implications of the limitations in functional capacity of the cerebellum in cretins. | en |
