Development of the Neural System and Clinical Paediatric Correlations

Question 1

When does human brain development begin?

Answer 1

In the 3rd week post-conception and continues well into adolescence and beyond

Question 2

What do genes determine in relation to the brain?

Answer 2

1. Correct sequence and evolution of the brain from conception to neuronal proliferation, migration and reorganisation
2. Development of dendritic and axonal interconnections
3. Development of synapses, receptors and neurotransmitters

Question 3

Factors in the intra-uterine environment that affect brain development?

Answer 3

Maternal health and disease (maternal PKU)

Insults which may be continuous/episodic throughout pregnancy, e.g: alcohol exposure

Placental function and foetal nutrition

Question 4

Factors in the extra-uterine environment that affect brain development?

Answer 4

Physical factors, e.g: nutrition, environmental toxins

Emotional and social factors, e.g: neglect and lack of stimulation

Question 5

Progression of brain development?

Answer 5

1. Embryonic period (conception to gestational week 8)
2. Foetal development (week 9 to 40/42)
3. Post-natal development

Question 6

Structure of the embryo at the beginning of the embryonic period?

Answer 6

2 layered embryo consists of epiblast (goes onto form the child) and hypoblast (forms placenta, etc)

There is primitive streak and primitive node

Question 7

Describe migration of cells during the embryonic period?

Answer 7

Migration of cells through streak and then rostral-caudal signalling; this is determined by nodal signalling

Question 8

What occurs during gastrulation?

Answer 8

Results in development of a 3-layered embryo:
• Ectoderm forms the skin, nails, hair and neural issue
• Mesoderm forms the muscle, bone, cartilage and vascular system
• Endoderm forms the gut and respiratory system

Question 9

What is the neural tube?

Answer 9

1st well-defined neural structure to form (at around days 20-27)

Neural progenitor cells forms the neural plate with a groove and then there folding and neural tube formation

Question 10

What is the ventricular zone?

Answer 10

Neural progenitors line the inside of the neural tube

Question 11

Which part of the neural tube becomes the central channel of the spinal cord?

Answer 11

Hollow centre of the tube becomes the ventricular system and central channel of the spinal cord

Question 12

Which part of the neural tube becomes the brain?

Answer 12

Anterior/rostral tube

Question 13

Which part of the neural tube becomes the spinal cord?

Answer 13

Caudal tube

Question 14

What sets the in the embryonic period for later development?

Answer 14

Neural patterning emerging in the embryonic period

There is complex and continuous refinement, e.g: the neocortex

Question 15

Signalling molecules in the mature neocortex?

Answer 15

Emx2 and Pax6:
• High conc. of Pax6 with low conc. of Emx2 induces progenitor to differentiate into motor neurons
• Low conc. of Pax6 and high conc. of Emx2 induces visual cortical neurons

Question 16

When does the foetal period take place?

Answer 16

Week 9 to term

Question 17

Changes of the brain during the foetal period?

Answer 17

Brain is initially smooth in contour and gradually develops its characteristic folded appearance (sulcal and gyral pattern); this is required to accomodate proliferating neuronal populations

Question 18

Sequence in which the sulci develop?`

Answer 18

Weeks 8-26:
• Primary sulci

Weeks 30-35:
• Secondary sulci

Weeks 36 and into the post-natal period and early infancy:
• Tertiary sulci

Question 19

When do neurons develop processes?

Answer 19

i.e: axons and dendrites - this occurs once neurones reach their target cortical regions

Question 20

Function of axons?

Answer 20

Transmit signals from neurons

Question 21

Function of dendrities?

Answer 21

Gather information and transmit to neurons

Question 22

Occurrence of programmed neuronal cell death?

Answer 22

Part of normal brain development, e.g: 50% of neurons will die (apoptosis), mostly pre-natally, and 50% of connections will be eliminated, post-natally and throughout life

Question 23

Events that occur as part of post-natal brain development?

Answer 23

1. Post-natal proliferation and migration

2. Myelination - increase axonal conduction rates

Question 24

What are OPCs?

Answer 24

Oligodendrocyte progenitor cells - develop processes that wrap around axons, i.e: myelin sheaths

Question 25

Why is early experience of the post-natal brain essential?

Answer 25

E.g: enrichement, as opposed to deprivation

For the emergence of normal neocortical patterns; when input is lacking, brain areas develop differently

Question 26

Describe what happens when there is monocular visual deprivation in early post-natal life

Answer 26

Alters patterns of recognition within the primary visual cortex; when both eyes are stimulated, pathways known as ocular dominance columns develop equally

Question 27

Consequences in the 1st few of life?

Answer 27

Usually not compatible with life

Question 28

Consequences of the neural tube not closing?

Answer 28

Anencephaly

Spina bifida

Question 29

Consequences of failure of brain vesicle formation?

Answer 29

Holoprosencephaly - forebrain of the embryo fails to develop into two hemispheres; it varies in severity, i.e: lobar, semi-lobar and alobar

Question 30

3 types of disorders of myelination?

Answer 30

1. Hypomyelination
2. Dysmyelination
3. Demyelination

Question 31

What is Pelizaeus-Merzbacher disease?

Answer 31

Most severe form that occurs with PLP1 gene (located on the X-chromosome) disorders that affects the growth of myelin sheaths

Question 32

Consequences of Pelizaeus-Merzbacher disease?

Answer 32

Progresses to severe spasticity and ataxia and a shortened lifespan

Question 33

Consequences of malnutrition?

Answer 33

Impact on:
• Brain growth and volume
• Myelination

There is a lack of energy, so there is also a lack of post-natal stimulation and experiences

Question 34

Development that occurs in adolescence?

Answer 34

Develop relations, identity, independence, self-confidence and self-control

But there is also profound emotional development, so it is a “risk-taking” period