Congenital Diseases Associated With Central Nervous System Flashcards

1
Q

How is the neural plate converted to the neural tube?

A

Neural plates elevate to form neural folds along the neural groove.

Neural plates fuse together

Morphogenesis occurs and the plates close to form a tube

There are two openings at the end of the tube
- anterior = ancephaly
- posterior = spina bifida

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2
Q

Where are the closures of the cranial and caudal neuropores located on a embryo?

A

Closure 1: between hindbrain and spinal cord

Closure 2: between forebrain and midbrain

Closure 3: most postural (anterior) portion of forebrain

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3
Q

What are the 2 modes of neural tube closure?

A

Primary neurulation and secondary neurulation

Both become continuous

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4
Q

What happens in primary neurulation?

A

Rolling up of the tube

Closure is by fold apposition then “zipping-up”

Finally, at cranial and caudal neuropores

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5
Q

What happens in secondary neurulation?

A

Tunnelling or hollowing of tail bud

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6
Q

What are the cellular and molecular mechanisms during primary neurulation?

A
  1. Shaping of the neural plate occurs by convergence/extension.
  2. Tubing requires bending at hinge points
  3. Cell wedging at hinge points: microtubules and actin filaments
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7
Q

Describe the process of convergence-extension

A

A process of lengthening by narrowing, which requires cells to become polarised, in the plane of cell layer.

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8
Q

What occurs in the Wnt-PCP pathway?

A
  1. Wnt (signalling molecule) is a ligand that binds to Frizzles (receptor transmembrane protein)
  2. frizzles change conformation to trigger a response inside the cell
  3. The reaction that occurs inside the cell involves bangles and celsr (co receptors necessary for signal transduction)
  4. Also involved are Dvl-3: which are cytoplasmic proteins activated by the Wnt binding
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9
Q

What happens when there are mutants in components of the Wnt-PCP pathway?

A

Using mice

The neural plate is abnormally broad with a non-bending region between neural folds - leading to chraniorachischsis.

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10
Q

Describe the process of cell wedging and apical constriction.

A

The neural plate folds and the notochord forms.

Then the neural crests are elevated

In apical constriction the remodelling of cytoskeleton at the apical cortex of the cell - by the Wnt-PCP pathway localising actomyosin to the apical surface, in a media lateral polarised way.

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11
Q

What is meant by cells in epithelium having apical-basal polarity?

A

specialised apical membrane facing the outside of the body or lumen of internal cavities, and a specialised basolateral membrane localised at the opposite side, away from the lumen.

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12
Q

What are the 3 most common defects in human neural tube?

A

Craniorachischisis: faliure closure 1

Anencephaly: cranial neuropores failure

Spina bifida: caudal neuropore failure

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13
Q

What environmental factors effect NTDs (Neuro tubule defects)?

A

Maternal diet
- vitamin deficiency/malnutrition
- high levels of sugar
- alcohol

Maternal obesity

Diabetes

Hypothermia

Tetratigenic agents
- valproic acid (VPA)

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14
Q

How can folic acid/folate deficiency cause NTDs?

A

Supplements recommended for pregnant mothers but sometimes it’s not enough.

The deficiency alone is not enough to cause NTDs, usually there is a predisposing mutation (these genes can be involved in folate metabolism or transport OR important for NT closure)

Folate mechanism that lead to NTD unclear

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15
Q

What are some mutations that can occur in folate related genes?

A

Transport molecules such as FLOR1, SLC46A1

Metabolising enzymes such as GLDC, MTHFD1

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16
Q

What is the function of folate or folic acid?

A

A essential nutrient involved in:

  • Neulotide synthesis
  • Serine-glycine inter conversion
  • Mitochondrial tRNA modification
  • methyl group biogenesis (proliferation, respiration, epigenetic modifications)
17
Q

What are some examples of genes that are important for NT closure?

A

Pax3,

ciliogenesis genes

18
Q

What is the function of inositol?

A

Essential building block of phosphoinositides
- structural components of the plasma membrane
- Key mediator of proliferation, cell motility, cell polarity, endocytosis

Involved in glucose metabolism and modulation of insulin levels

19
Q

How can inositol prevent NTDs in folate resistant experimental models?

A

Spina bifida NTD frequency is reduced in curly tail mouse mutants by inositol supplementation

Mechanism of action unclear