Week: 8 Lecture: 1 Brain Development

Things you should already know?

Prenatal development happens in 3 distinct stages – Germinal period, embryonic period (3-8 weeks - most vulnerable), rest is the Fetal Period  The neural tube, which will become the brain/spinal code, closes at 3 weeks (Germinal period) gestation. Systems that are undergoing rapid change are susceptible to disruption --- teratogens

What are Teratogen ?

Any agent that can produce a birth defect or increase the incident of a defect in a population Teratogenicity depends on

• Critical periods of development (timing)

• Dose of the drug/chemical

• Duration of exposure

• Early exposure to teratogens means the fetus may not be viable, but if exposed between 3-8 weeks are particularly sensitive and have an impact throughout the system – major congenital anomalies. Compared to 8 weeks and later

Describe Thalidomide as a teratogen?

Thalidomide → Impacted babies from day 21 -26 period - correlated what kind of development difficulties babies developed. (rat effect not equal to human effect) → now used for cancer treatments.

What are examples of teratogens and their impact on brain development?

Drugs → Alcohol - Fetal Alcohol Syndrome- where there is growth restriction, Facial Dysmorphology, microcephaly (reduced opportunity to engage and learn) and learning impairment. Can also be Fetal Alcohol Spectrum Disorder, wherein not all clinical criteria are met, but could have some symptoms suspected

Chemicals → Methylmercury - occurs in mothers whose diet primarily consists of fish → causes microcephaly, seizures and cognitive delays, movement related delays

Congenital ‘Minamata’ disease – a type of disease due to toxic dumping of mercury in water systems, essentially methylmercury poisoning Infection - mosquito born

Zika virus from infected mothers → causes microcephaly, eye damage, improper brain development which causes developmental delays.

How do you build a brain?

1. Neurulation - in which a neural tube is created

2. Neurogenesis (proliferation) - in which new neurons are spread

3. Migration - in which neurons move to their final destination

4. Circuit Formation -synaptogenesis (wherein neurons form new synapses ) , pruning

5. Myelination - building the fatty covering on the axon.

Describe Neurulation and its disruptions?

Wherein the neural tube closes from the middle outward - this happens in the 3rd week after conception. – tube develops from a plate Defects in this process result in Anencephaly (without brain) or Spina Bifida (wherein part of a spinal grows outside the body) It is prevented using folic acid – perinatal vitamins

Describe Neurogenesis and their disruptions?

Neurons develop about the 5th week, with neurogenesis peaking at 3-4 prenatal months. Other supporting cells are born each minute – gila Defects in the process - occur as a disruption of the cell proliferation process - e.g microcephaly - Rubella, Methylmercury, or Macrocephaly - congenital disorders, with genes that regulate proliferations that do not turn off.

Describe Migration and their disruption?

Neurons move from the proliferation zone to the location where they will reside inside the brain (between 6-24 weeks), sliding out the glial fibers. We don’t quite know how neurons know where they are supposed to stop. (jumping off the bus)

Defects in this process result in Lissencephaly (smooth brain) and

Agenesis of the Corpus Callosum (wherein nerve fibers connecting the left and right hemispheres (the corpus callosum) are partially or completely missing)

Describe Circuit formation and their disruptions?

Wherein circuits are formed – that is, axons and dendrites increase in number ‘synaptogenesis’ - this process is more rapid during the pre and early postnatal period. Synaptic Pruning also occurs in order to control this growth via experience throughout an infant's life. (this process occurs across the developmental period)

Defects in synaptic pruning can result in disorders like Williams syndrome - failures in pruning wherein synaptic density remains at infant levels, people have indiscriminate friendliness, high verbal and cognitive delays - normally occurs in elfin appearance. Failure in pruning and synaptic density remains

Describe Myelination and their Disruption?

Myelin is a lipid/protein substance produced by supporting cells → Myelins insulate axons so that signals can travel faster. Myelination describes the process by which cells get ‘myelined’ - bottom to top. Start of birth the process begins and by adolescence does the prefrontal cortex this happens DTi - identified myelinated fiber - (white = myelinated, grey = unmyelinated) Defects in myelination - does not really impact during the perinatal brain - but can be impacted by experiences.

Experience is important for long term change.