These are the summaries of the lectures of the course “The Developing Brain” of the
course “Brain and Mind” at the VU. Even though quality is tried to be ensured, mistakes
might have slipped in. Therefore, always use your own brain while studying and never
solely depend on one person to get through your exam. Also, I am not a native speaker,
but this course was in English, so my excuses for any mistakes.
There are some practise multiple choice (26) and open (3) questions at the end to help
you studying. Good luck �
,Content
A.The prenatal brain and its development..............................................................................................3
B.Teratogens...........................................................................................................................................6
C.Neurodevelopmental disorders...........................................................................................................8
D.Autism: sensory processing...............................................................................................................10
E.Autism...............................................................................................................................................11
F.Postnatal brain development.............................................................................................................12
G.Neurobiology of gender identity and sexual orientation...................................................................14
H.Drug abuse........................................................................................................................................17
I.Gender dysphoria...............................................................................................................................19
J.Schizophrenia.....................................................................................................................................20
K.Cognitive decline...............................................................................................................................22
L.Parkinson’s disease............................................................................................................................24
M.Clinical approaches for Alzheimer’s disease.....................................................................................26
N.Neurodegenerative disease...............................................................................................................27
O.Multiple choice questions.................................................................................................................29
P.Open questions..................................................................................................................................34
Q.Answers............................................................................................................................................35
, A. The prenatal brain and its development
Prenatal development
One example of a neurological development disorder is spina bifida. This means that a
baby is born with an open back, which will cause problems with the strength in the legs
and problems with the bladder.
In the development of the central nervous system, there are different stages: neural
induction, early patterning, cell differentiation, cell migration, and axon outgrowth.
Neural induction
During the neural induction, several processes take place. The neural induction is the
first process in the development of a child. The first process is the gastriculation, which
is the formation of three germ layers. The cell layers are called the mesoderm,
endoderm, and the ectoderm layer. Only the ectoderm layer will result in the nervous
system, although the skin comes from this layer as well.
The second process in neural induction is the neurulation, which is the formation of a
neural tube. In the ectoderm, a neural plate is formed. After this is folded, it ends in a
neural tube, which will rise into the central nervous system, namely the brain and the
spinal cord. The neural tube consists of stem cells. The proliferation of neural stem cells
causes the growing of the neural tube. Because these stem cells grow, the neural tube
will grow as well, in both the superior and anterior regions of the body: the head and the
tail of the spinal cord.
Early patterning
In the formation of the nervous system, cells are sorted to certain regions. This is a
process called the early patterning. A complex network of different signals causes the
patterning. Some signals are inductive, coming from other cells. These are also called
morphogens. The inductive signals are in interaction with the cells in the neural tube.
This leads to transcription factors. The factors can bind to DNA and therefore influence
the creation of certain proteins and alter gene expression.
One example of an inductive signal is the Sonic hedgehog (Shh). This signal is released
by the notochord, a structure posterior to the neural tube. The notochord is placed in
the mesoderm, which becomes the vertebral column. After the closing of the neural tube,
it defines the ventral region, which contains the motor regions. Other signals released
from the notochord are Noggin and Chordin. These signals will make sure that some cells
develop into neurons and do not develop into skin cells. Those signals are part of the
ventral-dorsal patterning.
Other ways of patterning are anterior-posterior patterning. Most of the knowledge comes
from the fruit fly. The transcription factors important for this patterning are the same for
the body of the fruit fly and for the formation of the neural tube. These factors are called
hox genes. Each segment of both the body of the fruit fly and the neural tube have a
different combination of these so called hox genes. The regulation of the hox genes is
regulated by retinoic acid (RA), which is an inductive signal. A small node of cells
releases RA: Hensen’s node. This node is formed during gastriculation. In the
beginning, Hensen’s node is located anterior in the ectoderm, but it travels via the
ectoderm to the posterior side, while releasing retinoic acid. The more anterior Hensen’s
node is located, the less RA is released.
Coming back to spina bifida: spina bifida is caused by problems with closure of the neural
tube. Potential causes are a lack in retinoic acid, which can be caused by a deficiency of
vitamin A or folic acid. An overdose of vitamin A can act as a teratogen, which can
cause malformations in embryos, mostly in the brain.
, Cell differentiation
After the first, basic layout of the central nervous system, different brain regions need to
be formed. The first step in this process is cell differentiation. Stem cells can
differentiate into neurons or into glial cells. There are two types of glial cells. The
oligodendrocytes create myelin, while the astrocytes form the blood-brain barrier.
Neural stem cells can form neuroblasts, which cannot split and develop into neurons.
Other stem cells can form new stem cells. These are called glioblast cells. This process
happens mostly in the ventricular zone (VZ), which exist alongside the ventricles in the
brain. This zone is only active during prenatal development. In the postnatal brain, there
are almost no zones where neurogenesis, the development of new stem cells and the
cell differentiation, takes place. In the subgranular zone (SZ), interneurons are formed,
which will migrate to the hippocampus. The hippocampus is one of the brain areas where
neurogenesis will take place after the prenatal phase. The neurogenesis is needed in the
hippocampus to form new memories and learn from experiences. In the subgranular
zone, projections are formed as well.
Dopaminergic cells are formed because of cell differentiation. Inductive signals trigger
transcription factors, which will define the fate of a certain subtype of dopamine neurons.
The loss of dopaminergic cells contributes to Parkinson’s disease.
Cell migration
When cells are differentiated, they must migrate to the appropriate are in the brain.
When someone is suffering from lissencephaly, there is an enlarged ventricle, no sulci
and gyri in the cortex and no white matter. Some treatment is possible, but the life
expectancy is only about twenty years.
Neuroblast cells move to their destination. Radial glial cells help with this process. The
cortex consists of six layers and each of these layers consists of different neurons. So,
the destination of the neuroblast cells depends on the nature of the cells. The deepest
layers are formed before the more superficial layers.
Several mutations in genes are know that can lead to problems in the migration of the
neuroblast cells. Genes needed in this process are either cell-adhesion molecules, which
interact with radial glial cells and are located on the cell surface. Other cells are
microtubule binding proteins, which forms the neuroblast cell morphology. If these cells
are mutated, problems can occur, such as microcephaly, which leads to a small brain,
or an ongoing migration, where not all layers of the cortex are filled. This is called
lissencephaly, as discussed above. Sometimes an inverted cortical layer is created, or a
double cortex. Life expectancy is about three years for most disorders.
Axon outgrowth
Much of what is known about axon outgrowth comes from studies with frogs. Neurons
are highly specialized and form axon and dendrites. If the neuron is still a neuroblast cell,
it will develop neurites. Only one, in most cases, of these neurites, will develop into an
axon. The other neurites will become dendrites. The axon consists of microtubules,
which are important for extension for the action. The growth cone is important for the
direction of the action and is highly dynamic. The direction is based on the interaction
with the environment. The first code discussed is contact repulsion. When the neurons
contact ephrins, the growth cone will move into a different direction. Contact
attraction, based on laminins, will lead to a movement into the direction of the cell.
Other factors are chemorepulsion and chemoattraction. These molecules, which are
not located on cells, will either repulse or attract a growth cone. All these factors lead the
growth of axons. On one point, all the axons will cross the midline. The midline in the
brain is the corpus callosum.
