Development of the CNS Flashcards
When does human brain development begin?
In the third post conception week
What does the information carried in genes determine once it is decoded?
Correct sequence and evolution of brain development
Development of dendritic and axonal interconnections
Development of synapses, receptors and neurotransmitters
What determines the intrauterine environment?
Maternal health and disease (ie maternal PKU)
Insults (i.e alcohol exposure, cytomegalovirus)
Placental function and foetal nutrition
What determines the extrauterine environment?
Physical factors = nutrition, environmental toxins
Emotional and social factors = neglect
Exposure to drugs, alcohol and other related substances
When is the embryonic period?
Conception to week 9
When does foetal development occur?
From week 9 until week 40/42
What are the different phases of development?
Embryonic period, foetal development, postnatal development, adolescent brain
What is the embryo like structurally in the embryonic period?
2 layered embryo, epiblast and hypoblast, primitive streak and primitive node
What occurs during the embryonic period?
Migration of cells through the primitive streak then rostral-caudal migration = determined by nodal signalling
What does gastrulation result in?
The development of a three layered embryo = ectoderm, mesoderm, endoderm
What does the ectoderm go on to form?
Skin. nails, hair, neural tissue
What does the mesoderm form?
Muscle, tone, cartilage and the vascular system
What systems in the body are formed from the endoderm?
The gut (GI) and respiratory systems
What is the first well-defined neural structure to form?
The neural tube = occurs at day 20-27
What do neural progenitor cells form in the neural tube?
The neural plate = line the inside of the neural tube
What is the ventricular zone?
The inside of the neural tube that is lines with neural progenitor cells
What does the hollow centre of the neural tube go on to form?
The ventricular system and central channel of the spinal cord
What does the brain form from in a foetus?
The anterior/rostral tube of the neural tube
What does the caudal tube of the neural tube go on to form?
The spinal cord
When does neural patterning begin?
During the embryonic period = sets the stage for later development
Is neural patterning an ongoing process?
Yes = undergoes continual and complex refinement
What does the mature neocortex have?
Distinct functional and structural areas
What are the signalling molecules present in the neocortex?
Emx2 and Pax6
What does a high concentration of Pax6 with a low concentration of Emx2 in the neocortex cause?
Induces progenitor cells to differentiate into motor neurons
What causes the induction of visual cortical neurons?
Low concentrations of Pax6 with high concentrations of Emx2 in the neocortex
What is the initial appearance of the brain at the beginning of the foetal period?
Smooth in contour (lissencephalic) = gradually develops folded appearance (sulcal and gyral pattern)
When do primary sulci form?
From week 8 to week 26
What are some examples of primary sulci of the brain?
Longitudinal fissure, sylvian sulci, cingulate sulci, parieto-occipital and calcarine sulci, temporal sulci
When do the secondary sulci form?
From week 30 until week 35
When do the tertiary sulci form?
From week 36 and into the postnatal period
Why is the development of sulci and gyri required?
To accommodate the proliferating neuronal populations
How do neuronal progenitor cells in the ventricular zone divide initially during the foetal period?
Symmetrically = two identical progenitor cells arise following division
What follows symmetrical neuronal progenitor cell division in the foetal period?
Asymmetrical neuronal progenitor cell division = produces one progenitor cell and one neuron
Where do progenitor cells remain?
In the ventricular zone = continue to divide and produce more cells
Where do neurons produced by progenitor cells in the ventricular zone migrate to?
The developing neocortex
What are some way that neurons migrate from the ventricular zone to the neocortex?
Somal translocation, using radial glial guides, tangential migration, signalling pathways
What does the migration of neurons from the ventricular zone to the neocortex result in?
An orderly six-layered structure with an inside-out arrangement of migrated neurons
What happens to neurons once they reach their target cortical regions?
They develop processes which allow them to communicate and transit information between neurons
What are the functions of axons?
Transmit signals from neurons
Form synapses when connected with another neuron
What determines the path of axons?
Guidance molecules
What is the function of dendrites?
Gather information and transmit it to neurons
What do multiple dendrites form around neurons
Arbors
Is programmed neuronal death normal?
Yes = part of normal brain development, 50% neurons die mostly prenatally, 50% of neuronal connections will be eliminated (postnatally and throughout life)
Is postnatal neuronal proliferation from the ventricular zone widespread or limited?
It is limited
Where are some areas that neuronal cells proliferate to postnatally?
Olfactory bulb
Dentate gyrus of hippocampus
Glial progenitors
What cells do glial progenitors produce?
Oligodendrocytes and astrocytes
What processes of brain development occur postnatally?
Postnatal proliferation and migration
Myelination
How are myelin sheaths formed?
Oligodendrocyte progenitor cells develop processes which wrap around axons
What is the benefit of having mulit-layered myelin sheaths?
Increases axonal conduction dramatically
What do myelin sheaths help to maintain?
Axonal integrity, neuronal size and axonal diameter
How does myelination occur?
Ina sequential manner from bottom to top and from the back to the front of the brain
When does myelination occur?
Mainly in the first two years of life but is ongoing into twenties
When are the core components of the CNS established?
In the prenatal period
What is required to develop the mature organisation of the brain?
Diverse inputs postnatally
What are the early experiences of the postnatal brain essential for?
The emergence of normal neocortical patterns
What happens when postnatal input to the brain is lacking?
Brain areas develop differently = specific patterns of development reflect the kinds of input the infant and child receive
What are the developmental tasks of adolescence?
Establish nurturing and intimate relationships
Development of identity, future perspectives, independence, self-confidence, social skills and self-control
Why is there a greater risk to health (ie from trauma or substance abuse) during adolescence?
Seen as time to take risks = important in development for teens to push boundaries and experiment
What occurs in the brain during adolescence?
Many synapses are eliminated, increase in white matter volume, changes in neurotransmitter systems
What is the state of brain development shortly after birth?
Almost fully grown = maturation of grey matter is on-going
How does maturation of the brain occur?
Occurs with synaptic priming and is experientially driven
What happens to white matter volume as the brain develops?
Concomitant increase = back to front process (sensorimotor cortex before frontal and prefrontal brain structures)
What do frontal and prefrontal cortex structures aid in brain development?
Higher cognitive functions, behavioural control, planning and assessing risk of decisions
What is anatomical rearrangement of the brain associated with?
Profound emotional and cognitive change
What do rising gonadal hormone concentrations during body cause in the body?
Physical maturations
How are pubertal hormones able to influence the brain?
Brain has many steroid hormone receptors
What effect do pubertal hormones have on the brain?
Affect brain restructuring by causing permanent reorganisation
What are the different effects that pubertal hormones have on the HPA axis in girls compared to boys?
Oestrogen makes girls more prone to stress
Androgens make boys more resilient to stress
What effect does monocular visual deprivation in early postnatal life have?
Substantially alters patterns of organisation within the primary visual cortex
What happens when both eyes are stimulated equally postnatally?
Pathways known as ocular dominance columns develop equally
What happens if one eye is blocked postnatally?
The columns representing the deprived eye shrink to thin stripes and the inputs form the active eye invade and subsume territory in the PVC normally occupied by the blocked eye
What are some conditions caused by abnormalities in neural tube formation?
Anencephaly, spina bifida, holoprosencephaly, double cortex
What is holoprosencephaly?
Failure of the brain vesicles to form
What are some disorders of myelination?
Hypomyelination, dysmyelination, demyelination
What does the PLP1 gene encode for?
A transmembrane proteolipid (myelin protein present in CNS)
What is the transmembrane proteolipid that PLP1 codes for responsible for?
Compaction, stabilisation and maintenance of myelin sheaths, oligodendrocyte development and axonal survival
Where is the PLP1 gene located?
On the x chromosome
What do mutations in the PLP1 gene cause?
A spectrum of disorders = most severe is Pelizaeus-Merzbacher disease
What does Pelizaeus-Merzbacher disease present with?
Presents in childhood with nystagmus, hypotonia and cognitive impairment
What does Pelizaeus-Merzbacher disease progress to over time?
Severe spasticity and ataxia = lifespan is shortened
What is another condition associated with PLP1 gene mutations?
Spastic paraparesis 2 = spastic paraparesis with or without CNS involvement, lifespan usually normal
What effect does malnutrition have on the brain?
Impact on brain growth and volume, and on myelination
What does the lack of energy and deprivation caused by malnutrition lead to?
Lack of postnatal stimulation and experiences = leads to disease and debilitation
Can the brain recover from the damage caused by malnutrition?
Yes, to some extent = some recovery is possible but there is a lasting impact on cognitive outcome and attainment
