Brain Development Flashcards

1
Q

Researchers have demonstrated that ______________ methylation of the agouti gene in mice will lead to ________________.

  • Decreasing; cognitive delays
  • Increasing; obesity and other health issues
  • Decreasing; obesity and other health issues
  • Increasing; cognitive delays
A

Decreasing; obesity and other health issues

(The correct answer is ‘decreasing; obesity and other health issues’ - when the agouti gene is methylated/silenced, we see typical development in mice, but when it is expressed (not methylated) we see obesity.)

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2
Q

You are studying cell differentiation in an in vitro model of the developing brain. You show that the same gene expression occurs in the cells you are studying, regardless of the environment in which the cells are placed. What can you conclude caused this differentiation?

  • A neurotrophic factor
  • An inducer
  • A morphogen
  • An intrinsic factor
A

An intrinsic factor

(The correct answer is ‘an intrinsic factor’ - all other choices are signals sent from other cells in the environment that can affect the cell in question. If a cell shows the same pattern of gene expression regardless of environment, this must be because of an intrinsic factor in the cell.)

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3
Q

If you blindfold a newborn kitten for a few weeks, the kitten will be blind. This occurs because neurotrophic factors are not being released by neurons functioning in early visual processing pathways which results in

  • failed migration of cells that would normally process visual information
  • apoptosis of cells that would normally process visual information
  • inactivation of cells that would normally process visual information
  • failed differentiation of cells that would normally process visual information
A

Apoptosis of cells that would normally process visual information

(The correct answer is ‘apoptosis of cells that would normally process visual information’ - during the sensitive period for visual processing, you must have proper communication between neurons in the visual processing pathway, otherwise they will undergo apoptosis.)

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4
Q

During a period of normal cell death, developing neurons survive if their target cells are releasing __________________.

  • Anti-apoptotic factors
  • Glucose
  • Cell adhesion molecules
  • Neurotrophic factors
A

Neurotrophic factors

(The correct answer is ‘neurotrophic factors’ - these are released when cells talk to each other, and help promote cell survival by working to suppress (often indirectly) the caspase cascade that would lead to apoptosis)

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5
Q

Both prenatally and throughout life, the process of methylation will ___________ the likelihood that a gene will be expressed.

  • Decrease
  • Increase
  • Decrease or increase, depending on the normal functioning of the gene
  • Have no effect on
A

Decrease

(The correct answer is ‘decrease’ - methylation effectively ‘silences’ genes because they cannot be transcribed after methylation has occurred.)

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6
Q

You experimentally deplete the concentration of noggin and chordin at the neural plate of the ectoderm. Doing so will cause:

  • Cells to migrate towards the neural tube
  • Cells to differentiate into skin cells
  • Cells to differentiate into neural cells
  • Cells to migrate to deep layers of cortex
A

Cells to differentiate into skin cells

(The correct answer is ‘cells to differentiate into skin cells’ - in your explanation, you must talk about the normal functioning of BMPs, which bind to transmembrane proteins and cause signaling cascades that tell a cell to differentiate into a skin cell. BMPs will preferentially bind to noggin and chordin, so when there is a high concentration of these at the neural plate, BMPs don’t bind to the transmembrane proteins and cells differentiate into neurons. Decreasing this concentration will increase the likelihood that BMPs bind to the transmembrane protein and lead to differentiation into skin cells.)

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7
Q

Neuron A left the ventricular zone after Neuron B. Which of the following is true?

  • Neuron A will form more connections than Neuron B
  • Neuron A is in a deeper layer of cortex than Neuron B
  • Neuron B will form more connections than Neuron A
  • Neuron B is in a deeper layer of cortex than Neuron A
A

Neuron B is in a deeper layer of cortex than Neuron A

(The correct answer is ‘Neuron B is in a deeper layer of cortex than Neuron A’ - the cortical layer a neuron migrates to is determined by its birthdate. The earlier a neuron is both, the deeper the layer - the cortex builds from the inside out.)

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8
Q

What is neurogenesis?

A

The proliferation of neurons

(Begins 42 days post conception.
Ends ~20 weeks)

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9
Q

Development of the central nervous system depends on

A
  • cell division (mitosis)
  • cell migration
  • cell differentiation
  • cell connections (synaptogenesis)
  • cell death (apoptosis)
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10
Q

Cells proliferate in the _______.

A

ventricular zone

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11
Q

How do cells migrate?

A

By using the radial glia and intercellular signaling

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12
Q

What determines a cell’s location?

A

Focusing on the cortex, birth date of cell is what matters for final location

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13
Q

What determines a cell’s identity?

A

Instrinsic and inducing factors

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14
Q

Cell type is dependent based on what?

A

Based on what genes a cell expresses

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15
Q

What are intrinsic factors?

A

cell-autonomous

genes in cell direct expression

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16
Q

What are inducing factors?

A

Signaling molecules from other cells

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17
Q

What two components make up inducing factors?

A
  • Inducer

- Morphogen

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18
Q

What is an inducer?

A

A substance causing differentiation

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19
Q

What is a morphogen?

A

A substance that can cause cells to differentiate into different types, based on its concentration.

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20
Q

In the CNS, most neuronal differentiation is based on ______.

A

local cell-cell interactions

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21
Q

If BMPs act –> ____

If BMPs inhibited –> _____

A

If BMPs act –> skin

If BMPs inhibited –> neurons

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22
Q

How do neurons develop and maintain synaptic connections?

A

Once a cell has made it to its final location, it can extend its axon

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23
Q

What components make up a growth cone?

A
  • Central core
  • Filopodia and Lamellipodia

(Filopodia can use structural support to guide growth.)

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24
Q

What determines the cues a particular growth cone is getting?

A
  • Cell-Cell interactions

- Molecular matching between target cells and growing axons (modified through activity)

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25
Q

Sperry argued this was evidence that

A
  • Axons have differential markers that correspond to markers on a target cell
  • Axonal growth is directed by markers to establish specific connections
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26
Q

After axons reach appropriate targets, ______ begin to form.

A

synapse

Completes ‘hard wiring’ of CNS

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27
Q

Whether connections get strengthened depends on _______.

A

intercellular interactions

28
Q

Elimination of synapses AND of neurons occurs as part of the __________ process.

A

developmental

29
Q

What causes some connections and neurons to survive, but not others?

A

Neurotrophic factors

(If neurons are in communication with each other, you are protecting them from dying.
Neurotropic factors are released when neurons communicate from the postsynaptic neuron to the presynaptic neuron. They inhibit the caspase family.)

30
Q

What are the functions of neurotrophic factors?

A
  • Prevent apoptosis –> survival of presynaptic neuron
  • Can facilitate synapse rearrangement

(important of experience!)

31
Q

Lack of neurotrophic factors leads to ______.

A

cell death

32
Q

What is apoptosis?

A

Natural cell death

Clears out neurons that are not important. The environment drives this decision.

33
Q

What are the steps of apoptosis?

A
  • Blebbing
  • Cell shrinkage
  • Condensation of chromatin
  • Phagocytosis of cellular remains
34
Q

There are many pathways to get to apoptosis, but all have something to do with…

A
  • Mitochondria

- Ca2+ concentration

35
Q

What are the pro-apoptotic factors?

A
  • cytochrome c
  • apoptosis inducing factor (AIF)
  • procaspase-9
  • Smac/DIABLO
  • endonuclease G

(If released, they cause apoptosis.)

36
Q

Each pro-apoptotic factors work in a different way, but generally activate _______.

A

caspases

Caspases are protein dissolving enzymes

37
Q

Cascade of events destroys ______ and _____ and cell cannot survive.

A

proteins and DNA

38
Q

What are the scientific steps of apoptosis?

A
  1. Apoptotic signals
  2. Mitochondrial Ca2+ overload
  3. Fragmentation of mitochondrial network
  4. Release of proapoptotic factors
  5. Apoptosis
39
Q

What are protective factors?

A

Substances that can inhibit influx of Ca2+ into mitochondria

(Substances that can inhibit caspases often indirectly.
Prevents apoptosis from occurring.)

40
Q

When do epigenetic influences occur?

A
  • During prenatal development
  • Across the lifespan

(Influenced by experience - what you eat, what you are exposed to, whether you exercise, etc)

41
Q

How do genes get turned on/off?

A

By the process of methylation.

Methylated genes cannot be expressed.

42
Q

What is methylation?

A

The process by which methyl groups get added to DNA.

43
Q

What determines whether the agouti gene is methylated?

A

Maternal diet

When the agouti gene is expressed, it leads to obesity.

44
Q

What is BPA (bisphenol A)?

A

It is used to make polycarbonate plastic and reduces the methylation of agouti genes.

45
Q

How does the hypothalamic-pituitary-adrenal (HPA) axis work?

A
  1. Stress initiates endocrine cascade in hypothalamus.
    (Hypothalamus 4 F’s)
  2. Pituitary releases ACTH
    (Adrenal corticotrophic hormone)
  3. Adrenal gland releases GCs (glucocorticoids)
  4. GCs act as a negative feedback
46
Q

What occurs when there are small levels of stress?

A

Cortisol is broken down before it reaches the fetus.

47
Q

What occurs when there are large stressors or consistent low-level stressors?

A

It impacts fetal development.

Infant will be born with an HPA axis that is not functioning properly. Impacts more in the 2nd and 3rd trimester.

48
Q

What does the hypermethylation of NR3C1 encode for?

A

glucocorticoid receptor (GR) production

(Important for negative feedback loop)
(If it is over-methylated, there is not enough production of GR and this will lead to a hyperactive HPA axis.)

49
Q

What is the hyperactivity of the HPA axis associated with?

A

Abnormal cortisol functioning which is detrimental pre- and postnatally

(Less effective negative feedback loop because it is associated with stress regulation.)

50
Q

In rats, maternal care can affect ______.

A

Methylation

This is desirable because when the agouti gene is silenced, it leads to a thin, healthy individual.

51
Q

What can pup licking and grooming do?

A

Decrease methylation of GR gene in hippocampus

52
Q

Describe the Bucharest Early Intervention Project?

A

A randomized clinical trial of 136 children.

  • Foster homes
  • Remain institutionalized
  • Control group: children reared in biological families

The goal of the experiment was to track brain development. Researchers wanted to see the extent to which the hazards children encountered due to psychosocial deprivation could be ameliorated by placement in a better environment.

(Those without proper maternal care had more methylation of the SLC6A4 gene and developed poorly.)

53
Q

What does the SLC6A4 gene encode for?

A

The 5-HT (serotonin) transporter

54
Q

Genetic and stress-related alterations in the SLC6A4 gene associated with?

A

Early life adversity and long-term health outcomes

55
Q

Adverse environment can lead to decreased methylation of the SLC6A4 gene. What can this lead to?

A

Dysregulation in 5HT signaling

56
Q

What are the 3 components to an early visual experience?

A
  1. Sensitive period
  2. Binocular deprivation
  3. Monocular deprivation
57
Q

What occurs when deprived during the sensitive period?

A

Blindness

Example of binocular deprivation

58
Q

What is monocular deprivation?

A

The deprived eye will not respond to input

59
Q

Neurons that _____ together, ____ together

A

fire; wire

60
Q

How do blind individuals ‘see’?

A
  • Braille reading
  • Passively feeling Braille
  • Activation in visual cortex
61
Q

Do our brains treat information learned through our own actions differently than information learned through observation of another person’s actions?

A

Yes. The type of input we get shapes the connections and neural activity in our brains.

62
Q

How do we process information and engage with the environment?

A

Through the compartmentalization of the brain

63
Q

DIABLO inhibits ____.

A

IAP

(This is an inhibitor of apoptosis protein. Normally the IAP are making sure that the caspase cascade cannot occur. DIABLO makes it so IAP cannot inhibit the caspase and the cascade occurs in the inner membrane space.)

64
Q

What does the Bcl-2 protein family do?

A

It is able to regulate calcium influx.

Bcl-2 protein family helps with the release of Ca2+ in the ER

65
Q

What is epigenetics?

A

It is modifying the expression of a gene without modifying the genome.