Quality and quantitative morphological changes in the brain of adult mice used as an animal model of fetal alcohol syndrome
Date
2017
Authors
Olateju, Oladiran Ibukunolu
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Abstract
We examined the effect of chronic prenatal alcohol exposure on the qualitative and
quantitative changes in the brain of C57BL/6J mice once they had reached early adulthood
(56 days post-natal). Pregnant mice, and their in utero litters, were exposed to alcohol,
through oral gavage, on gestational days 7 – 16, with recorded blood alcohol concentrations
averaging 1.84 mg/ml (chronic alcohol, or CA, group). Two control groups, an oral gavage
sucrose control group (chronic alcohol control, or CAc, group) and a non-treated control
group (NTc group), were also examined. Using appropriate antibodies specific for the neurons
or nuclei of interest, the present study compared morphologically and quantified (I) the
neuronal cell proliferation and the appearance of immature neurons in the hippocampal adult
neurogenesis, (II) the changes in the PMBSF barrel sizes in the somatosensory cortex, (III)
the cortical organization, cell number and cell sizes of cerebellar interneurons in the vermal
cerebellum, and (IV) the nuclear organization, cell number and cell sizes of four specific
clusters of nuclei for the control and regulation of sleep-wake cycle in the brains of all the
experimental groups. The stained neurons and nuclei of interest were consistent in all the
three experimental groups. The quantitative analyses showed that alcohol, in comparison with
the two controls, had (I) no strong effect on the proliferative process but significantly reduced
the numbers of immature neurons in the hippocampus, (II) no effect on the barrel sizes from
the different measured parameters, despite a reduced barrel size in the alcohol group, but there
was significant size reductions in barrel rows D and E, (III) no effect on the cell densities of
Nissl and PV+ stained neurons in the molecular layer and the cell sizes of Purkinje cells
immunolabelled with CB antibody, and (IV) no effect on the numbers of ChAT+ neurons,
TH+ neurons, OxA+ neurons, however there were significantly larger OxA+ neurons and
significantly smaller ChAT+ neurons while the TH+ neuron size was not significantly
different. Some of these results are consistent with other studies that utilized FAS rodent
models thus suggesting the suitability of this mouse model for FAS studies. The significant
findings could help explain the reasons for the neurodevelopmental and behavioural problems
that are common to FAS subjects. The neuroanatomical evidence presented in this study could
open avenues for interventions to improve the quality of life of FAS and FASD children.
Description
A Thesis submitted to the Faculty of Health Sciences, University of the
Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree
of
Doctor of Philosophy
Johannesburg, 2017