Neurodevelopment Flashcards
Day 1 of human embryo
Human zygote consists of a single cell.
Day 2 of human embryo
This cell divides and continues to divide.
Day 15 of human embryo
Emerging embryo is formed by several sheets of cells with a raised area in the middle called an embryonic disc.
Day 21 of human embryo
Primitive neural tissue forms the neural plate.
What is a neural tube
- Cells in the neural tube are thought of as the nursery for the rest of the CNS!
- Cylinder type space in the neural tube remains open;
- Gives rise to the brain’s ventricles and the spinal canal.
Day 49 of human embryo
Embryo resembles a miniature person
Day 100 of human embryo
Brain begins to resemble that of a human.
7 months of human embryo
Formation of gyri and sulci.
9 months of human embryo
Very distinct human brain, although cellular structures is still much different than adult brain.
Neural Stem Cells
- Multipotential cell;
- Lining the neural tube;
- Extensive capacity for self renewal;
- In adults, neural stem cells line the ventricles forming the sub ventricular zone;
- Neural stem cells give rise to progenitor cells (aka precursor cells).
What can Progenitor be divided into
Neuroblasts
Glioblasts
What is Neuroblasts
develop into mature neurons;
What is Glioblasts
develop into mature glia.
How can we ensure stem cells become mature neurons/glia?
Newborn cells use chemical signals & genetic instructions throughout the
developmental process.
1.Prolactin – naturally occurring hormone that helps replace lost neurons in animal models;
2. Gene transcription – turning on the correct genes that dictate a stem cell will become a neuron and not a skin cell, for example;
3. Epigenetic
Neurotrophic Factors
Chemical compounds that act to support growth and differentiation of neurons;
- Keeps adult neurons alive and healthy;
1. Epidermal Growth Factor (EGF) and Basic Fibroblast Growth Factor (bFGF)
What is Basic Fibroblast Growth Factor (bFGF)
stimulates progenitor cells to produce neuroblasts.
What is Epidermal Growth Factor (EGF)
stimulates stem cells to produce progenitor cells;
What are Neuroblasts
Neuroblasts serve as an all-purpose neuron until they are exposed to certain growth factors in other areas.
These chemical messengers will dictate the fate of the neuron.
Neurodevelopmental Stages
- Cell Birth to neurogenesis, gliogenesis;
- Cell Migration to traveling to final destination;
- Cell Differentiation to developing specific tools/skill set;
- Cell Maturation to dendritic development, axonal growth;
- Synaptogenesis to formation of synapses;
- Cell Death to apoptosis/pruning;
- Myelogenesis to formation of myelin sheath.
Neurogenesis
Largely complete by 5 months (prenatally);
During this time, brain is resilient to injuries (i.e. teratogens) and/or trauma;
Note: resilient ≠ resistant.
Cell Migration
Begins just after neurogenesis is complete;
Lasts for ~6 weeks.
Cell Differentiation
Begins during migration, continues after
migration is complete;
More-or-less complete at time of birth.
Cell Maturation
This process occurs for years, well into adulthood; Growth of dendrites and axons;
Synaptogenesis
Each neuron begins forming its own networks; Can synapse with hundreds or thousands of other neurons;
Cell Death
If you don’t use it, you lose it;
Myelogenesis
Neuronal networks become more efficient in their communication;
Sign of neurodevelopmental maturity; Occurs well into adulthood;
Subventricular Zone (SVZ)
- SVZ contains a primitive map of the cerebral cortex;
- Cells formed in certain regions of the SVZ migrate to certain cortical locations.
Radial Glial Cells
- Form a path that extends from the SVZ to the surface of the cortex;
- Undifferentiated progenitor cells follow this path.
Cortical layers form from inside out. The most inner layer (VI) are first to form.
Q: How do neurons know when to stop? (i.e. cortical thickness)
How do cells get to their final destination?
Intercellular signals (i.e. between cells) progressively restrict the choice of traits a cell can express. Therefore, the emergence of a cell type is a combination of genetic instructions, timing and signals from neighboring cells in the local environment.
A maturing neurons needs:
- Dendritestoprovidesurfacearea for synapse formation:
- Branching of dendrites (arborization); - Growth of dendritic spines (μm.day-1). - Axon extending to appropriate target to initiate synapse formation
- Occurs very rapidly (mm.day-1);
- Various molecules attract or repel axon tip, thus guiding it through a very complex terrain.
Growth Cones
Santiago Ramón y Cajal defined growing axons as growth cones.
Filopod
Growth cones extend shoots called filopod (e.g. fingers on a hand);
When filopod reaches an appropriate target, the others follow.
Growth cones are responsive to:
- Cell-adhesion Molecules (CAMs) Secreted from cells or lie on cell surface.
- Tropic Molecules
Secreted from target cells;
Carry “come here” or “go away” message; Netrin (L. to guide) is the only known group.
Synaptic Development
Human brain contains about 1014 synapses;
- The amount and array of synaptic connections is thought to be guided mostly by environmental cues and signals;
- At 7th gestational months, these connections are rather simple;
- At birth, the number of synapses increases dramatically;
- By 2 – 4 months, the number of synapses in the visual cortex doubles, and continues to increase for years.
Synaptic Pruning
The brain uses apoptosis as a method of pruning
- Genetics signals, experience, hormones, stress, etc. are all factors that can initiate apoptosis;
- ~42% of all synapses in human cortex are lost.
Neural Darwinism
- Competition drives neuronal loss;
- Environmental pressure leads to competition amongst neurons.
Nerve Growth Factor (NGF)
is a neurotrophic factor produced by cells that regulate neuronal survival;
- Therefore, neurons that are deprived of NGF will undergo apoptosis;
- Those neurons who make connections early on will be nourished with NGF and other growth factors.
Generally, the cortex continues to thin from ages 5 to 20
The exception to this is in language centers
- Unique role of language processing and nature of language-learning processes makes this area an exception to this rule.
Myelination
Frontal lobe is the last brain region to mature
- Pruning occurs into the 20’s
Process of myelination can be used as an index of neuronal maturity.
Early-myelinating areas control simple movement, while late-myelinating areas control highest mental function.
Experience & Cortical Organization
Donald Hebb (1947)
- Took some laboratory rats home and let them grow up in his kitchen;
- Control group stayed at McGill University;
- The ‘home’ rats had many more experiences then the ‘cage’ rats;
- On subsequent intelligence tests, the home rats outperformed the cage rats;
- Hebb concluded that experience must influence intelligence in some way;
- Hebb’s experiment lead to the development of Sesame Street which aimed to offer enrichment for children.
Experience & Cortical Organization
Stimulation is extremely important during development and cortical organization
- Tactile stimulation has been shown to increase the growth rate of pre-mature babies in an incubator;
- Brushing infant rats for 15 minutes 3 times daily speeds up growth and development;
- Tactile stimulation of infants is important for forming bond with caregiver;
- Experience changes structure of neurons, especially cortical neurons;
- Processing of sensory information increases number of synapses and astrocytes.
Abnormal Experience & Brain Development
Donald Hebb (1951), Sensory Deprivation Studies
- Placed Scottish terrier in the dark with as little stimulation as possible and compared them to ‘normal’ dogs;
- Later in life, deprived dogs didn’t pay attention to other dogs or humans;
- Lost sensation of pain;
- Performed very poorly on intelligence test;
- Depriving young animals of visual input or maternal contact has devastating; consequences on behavioral development (and presumably brain development).
Abnormal Experience & Brain Development
Austin Riesen (1982)
- Extensively studied animals raised in the dark;
- Atrophy of dendrites in visual cortex, which is the opposite of what happened to the enriched rats;
- Eye still worked, but functionally blind.
Harry Harlow (1950’s)
- Monkeys raised with no maternal/paternal contact showed abnormal intellectual and social behaviors in adulthood;
- There are a number of hormonal and neurobiological abnormalities among motherless monkeys.
Romanian Orphans (1970’s)
- Birth control & abortions were outlawed;
- Fed and clothed, but virtually no environmental stimulation;
- Motor and cognitive impairments;
- Age of adoption dictated extent of recovery.
