Time-course changes in cell proliferation, cell differentiation and cell death in the avian, amphibian and mammalian brains
Date
2019
Authors
Nkomozepi Pilani
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Abstract
This thesis presents a collection of four related studies that were designed to
investigate the occurrence and dynamics of postnatal neurogenesis in animal
species derived from three different vertebrate taxa: mammals, avians and
amphibians. This work was prompted by the observation that non-mammalian
vertebrates are able to regenerate functional neural tissue following injury or
experimental ablation of whole or parts of the brain parts, in striking contrast to
mammals where neural tissue is seldom replaced following injury. The origin of this
the remarkable difference is poorly understood but differences in patterns of neuronal
stem cell proliferation and neurogenesis are thought to be involved. Therefore, this
interclass work was designed to determine neurogenic compartments in the
amphibian, avian, and mammalian brain and to determine time-course (defined as the
increasing chronological age across the different life-history stages of each animal)
changes in neurogenic activity (neuronal stem cell proliferation, differentiation and
neuronal incorporation) in each compartment. The African clawed frog (Xenopus
laevis), Japanese quail (Cortunix cortunix Japonica) and BALB/c mouse (Mus
musculus) were used in this study as representative models for the amphibian, avian
and mammalian vertebrates respectively.
In study 1, a qualitative evaluation of proliferative sites and brains areas that
incorporate new neurons in the Japanese quail brain at post-hatching ages 3 to 12
weeks was carried out using immunohistochemical methods. Proliferating cells were
observed mainly in the olfactory bulb ventricular lining, telencephalic ventricular
zones, and cerebellum. Fewer proliferating cells were also observed in the
hypothalamus, thalamus, and bed nucleus of the stria terminalis. Newly formed
neuroblasts were observed incorporated into the olfactory bulb, telencephalon, and
cerebellum. Furthermore, these neuroblasts were observed throughout all the
regions of the pallium (except for the entopallium and arcopallium); septal nuclei, and
striatum. Fewer neuroblasts were also observed in the hippocampus and bed
nucleus of the stria terminalis. The density of proliferating cells and neuroblasts in all
brain areas declined with post-hatching age.
Since study 1 established that the telencephalon exhibited the highest neurogenic
activity, study 2 was designed to quantitatively analyse how neuronal incorporation in
the Japanese quail telencephalon changes with age and life-history stage. In all the
eight areas of the telencephalon quantified, the numbers of neuroblasts were strongly
negatively correlated with post-hatching age. Furthermore, the numbers of
neuroblasts in the same brain areas were higher at juvenile compared to sub-adult
and adult life-history stages. This study revealed that neuronal incorporation in the
quail telencephalon is widespread but declines with post-hatching age. In addition,
the most dramatic decline in neuronal incorporation in all the telencephalic areas
quantified occurred from the 7th week just after the quails attained sexual maturity.
Study 3 was designed to qualitatively and quantitatively determine how age (1-12
weeks) and life-history stage affects neurogenesis in the male BALB/c mouse brain
using immunohistochemical methods. Proliferating cells were mainly observed in the
olfactory bulb, rostral migratory stream, subventricular zone of the lateral ventricle, and subgranular zones of the dentate gyrus. In addition, fewer proliferating cells
were also observed in the neocortex, cerebellum, and tectum. Newly formed
neuroblasts were found in similar brain regions as the proliferating cells except for the
cerebellum and tectum. The numbers of both proliferating and newly formed cells
sharply decreased with increasing age or progression through life-history stages in
all the neurogenic areas of the BALB/c mouse brain.
The objective of study 4 was to qualitatively and quantitatively determine how
proliferating cells and newly formed neuroblasts in the post-metamorphic African
clawed frog brain change with age and the life-history stage. Proliferating cells were
observed mainly in the ventricular linings of the olfactory bulb, telencephalon, ventral
hypothalamus, preoptic region, and metencephalon adjacent to the cerebellar granule
cell layer. Newly formed cells were observed in the parenchyma of the olfactory bulb,
telencephalon, ventral hypothalamus, and cerebellum. In the telencephalon, newly
formed cells were concentrated mainly in the striatal and septal areas although fewer
cells were also observed in the lateral, medial, and dorsal pallial areas. In all the
quantified areas of the post-metamorphic brain of the African clawed frog, the
numbers of proliferating and newly formed cells were strongly negatively correlated
with age. Furthermore, both these cells were higher in the juvenile frogs compared to
subadult and adult frogs.
In conclusion, this work established that the ventricular lining is the main site of
neuronal birth in all the vertebrate species investigated. In the amphibian brain,
neuronal birth takes place in the ventricular lining of the olfactory bulb, telencephalon,
diencephalon, and rhombencephalon. In the avian brain, neuronal birth is restricted to
the ventricular lining of the olfactory bulb and telencephalon, and cerebellum. In
mammals, however, neuronal birth is restricted to the telencephalon, specifically the
subventricular zone of the lateral ventricles, the rostral migratory stream, and the subgranular zone of the dentate gyrus. This reflects a phylogenetic reduction in the
brain regions exhibiting proliferative activity.
Similarly, neuronal incorporation is more widespread in the amphibian and avian
brains compared to the mammalian brain. In the amphibian brain, new neurons are
incorporated in the olfactory bulb, telencephalon, diencephalon, and cerebellum. ln
the avian brain, neuronal incorporation takes place mainly in different parts of the
telencephalon, and to a lesser extent the olfactory bulb and cerebellum. In mammals,
neuronal incorporation is mainly restricted to the olfactory bulb and the hippocampal
dentate gyrus. It, therefore, appears that as vertebrates evolve, there is a reduction in
the number of brain regions incorporating new neurons.
In addition, this work also revealed that neurogenesis decreases with age in all the
vertebrates studied. In the amphibian and avian brains, the rate of neurogenesis is
relatively stable during the juvenile period and then declines steeply during the
transition from sub-adult to adult life-history stages as the animal attains sexual
maturity. In mammals, however, the decline in neurogenesis is very rapid and steep
from early postnatal life to adulthood. Thus neurogenesis declines at a slower pace in
amphibian and avian brains compared to their mammalian counterparts.
Description
A thesis submitted to the faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the Degree of Doctor of Philosophy