الفهرس 
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Abstract
The last decade of the twentieth century was named the decade of the brain by the international scientific community, and the beginning of the twenty-first century is regarded as the days of neuroscience. Thus it has become especially important to study the effects of environment on brain function. The wide exposure to fluoride makes studies of its effects on different organs very important. Many of the biological effects of fluoride have been extensively studied but the brain injury produced by this substance has received less attention.
The aim of this work is to study the histological, ultrastructural changes that might occur in the prenatal and postnatal development of the cerebellar cortex in the albino rat after oral intake of sodium fluoride.
Fifty adult albino rats, ranged between 200 — 250 gm were used as forty females and ten males. The female rats were divided into two groups. Prenatal and postnatal groups and each one subdivided into control, sham and experimental groups. Control subgroup was ten pregnant rats, were lift till the time of the experiment without any administered drugs. The control sham subgroup was 10 pregnant rats, received 1 ml distilled water. Treated groups were 20 pregnant rats, received sodium fluoride orally (dissolved in distilled water) at a dose of 50mg/ kg/ day. Both groups were given the dose by gastric tube from the 10th day of pregnancy and throughout the lactating period, weaning time for 2 weeks. Samples from cerebella were taken and processed for light and electron microscopic investigation.
In the control group, the cerebellar cortex atl 8 days prenatally, 20 days prenatally and at birth was consisted of three layers; the external
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germinal layer, the molecular layer and the Purkinje cell layer. The external
germinal layer increased in the thickness from 18 days prenatally till the age
of 14 days where it reached its maximum thickness. It began to decrease in
thickness in the 14 days to completely disappear on postnatal day 21.The
molecular layer appeared at birth as a hazy area containing migratory cells
and increased in the thickness till the 28 days due to accumulation of nerve
fibers, which became more prominent with age. The Purkinje cells were
noticed at birth as large rounded cells, larger than the surrounding cells,
arranged in multicellular rows and formed the most cellular element in the
cortex of the newly born rats. At 7 days, they were oval or fusiform in shape
arranged in a more or less monocellular row between the molecular and the
internal granular layer. At 14 days, the Purkinje cells attained their adult form
with flask-shape appearance and many branched dendrites. At 28 days and 60
days, the cell body took the smooth elongated piriform shape, and the cells
completed their neurogenesis. The internal granular layer was significantly
increased in thickness from postnatal day 7 till 60 days; at first the cells were
sparsely arranged, but at the age of 15 days, the main bulk of cells were
formed, they were collected in groups leaving clear spaces among these
groups of cells were (cerebellar glomeruli) with appearance of Golgi cells.
The cells were more densely packed together especially at 60 days after total
disappearance of the external germinal layer with well defined cerebellar
glomeruli among them.
In electron microscopic observations of all ages: The granule cells of
internal granular layer were appeared with smooth outline, heterochromatic
nucleus. The myelinated axons had regular outline of the myelin sheath
contained healthy mitochondria with apparent cristae. There were
unmyelinated axons with intact mitochondria. The Purkinje cells were seen
with intact nuclei mitochondria, and the rough endoplasmic reticulum.
In fluoride treated groups, there were a delayed foliation and fissure formation in the pups at all ages. The external germinal layer showed a significant thinning in thickness at 18 days, 20 days prenatally and at birth. This significant decrease in thickness progressed till the 14 days. At 21 days, normally the external germinal layer starts to disappear. At all ages, external germinal layer contained some of degenerated cells with vacuolations. The molecular layer manifested a decrease in thickness till the age of 60 days. It contained fewer cells and showed areas of matrix vacuolations. The pathological changes in the Purkinje cells were the most obvious changes induced by exposure to sodium fluoride. There were Purkinje cells at all ages. At 7 days and 14 days, there was a delayed alignment of the Purkinje cells, and this was the first sign of immaturity. At 21 days, there was a smaller cell body with many degenerated cells in the single row of Purkinje cells. At 28 days and 60 days, there were more degenerated cells of the Purkinje cell layer with astrocytic proliferation near the degenerated Purkinje cells with areas of focal loss and vacuolations. The internal granular layer had fewer cells at all ages. However, they appeared clumped on each other with disappearance of the regular cerebellar glomeruli among them. Many cells of the internal granular layer showed areas of vacuolations.
In electron microscopic observations of all ages of fluoride treated groups: There was shrunken Purkinje cell with heterochromatic nucleus, irregular outline of nuclear envelope, vacuolations throughout, dilated rough endoplasmic reticulum, dilated Golgi apparatus, destructed mitochondria. The unmyelinated axons were noticed with vacuolations and the myelinated axons had indentation of its myelin sheath. There were degenerated granule cells with heterochromatic nucleus, astrocytic cells were noticed with large pale nucleus.
from this study, we conclude that the ingested fluoride produced structural and ultrastructural changes in the different layers of cerebellar cortex. Therefore, we recommend a restricted fluoride dose in water supply
and in medical prescriptions.