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Brain PD > Week 4 part 1 > Flashcards

Week 4 part 1 Flashcards

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1
Q

When does brain development start?

A

4th week of gestation after formation of neural tube

Neural plate fold over and creates the basic fore-, mid- and hind-brain

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2
Q

When is the male brain weight heavier than female (~10%)?

A

From 2 years onwards

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3
Q

How old is the brain when the child is born?

A

8 months

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4
Q

What is the brain growth and differentiation controlled mainly by?

A

Genes

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5
Q

What is key to getting the best of the brain?

A

The best prenatal environment possible

In the early weeks of development, that means having a mother who is stress-free, eats well and stays away from cigarettes, alcohol and other toxins

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6
Q

What happens towards the end of the brain-building process, when the fetus becomes able to hear and remember?

A

Sounds and sensation also begin to shape the brain

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7
Q

When does the brain get smaller?

A

20 years old

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8
Q

What is neurulation?

A

Formation of neural tube

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9
Q

What is the process of neurulation?

A
  1. Neural plate is formed from the thickening of the dorsal ectoderm
  2. Nueral groove with neural fold either side occur at midline of neural plate along notochord
  3. Neural plate fold to form the neural tube
  4. Neurulation proceed bidirectionally from mid portion to cranial and caudal ends
  5. Thickening of the neural tube wall forms the brain and spinal cord. the lumen of the tube forms the ventral and central canal
  6. Neuroepithelial cells forming neural tube wall give rise to neurons and macroglia (astrocytes, oligodendrocytes, ependymal cells)
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10
Q

When does the formation of nervous system begin?

A

During third week of gestation

When the neural plate develops from thickening of embryonic ectoderm

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11
Q

What can Glia be classified as?

A

Different subsets, based on their morphology, function and location in the nervous system

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12
Q

What are the 2 main glial subset in CNS?

A
  1. Microglia
  2. Including astrocytes and oligodendrocytes
  3. macroglia
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13
Q

What does glia have?

A
  1. ‘yolk sac’ macrophage based source, from where they colonize the brain during prenatal development
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14
Q

Where are microglia derived from?

A

Neural lineage

Produced after initial neuronal birth wave o

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15
Q

What are oligodendrogenesis?

A

process that is regulated by extrinsic and intrinsic factors. The main external stimuli are morphogens, growth factors and extracellular matrix elements, while the internal stimuli important for oligodendrocyte formation are transcription factors and epigenetic regulators.

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16
Q

What are all from the neural stem cells?

A
  1. Neurons
  2. Astrocytes
  3. Oligodendrocytes
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17
Q

What can neural stem cells split into?

A
  1. Neuronal progenitor (becomes neurons)

2. Glial progenitor (which becomes astrocytes/oligo’s)

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18
Q

What does neuron give rise to?

A

Majority of the brain cells

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19
Q

Where is blood supply from?

A

Mesoderm formation

Has Hemangioblasts

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20
Q

What are hemangioblast?

A

Multipotent precursor cells that can differentiate into both hematopoietic and endothelial cells

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21
Q

What is hematopoietic cells surrounded by?

A

Endothelial cells

Part of blood vessels and they form capillary plexus in terms of orientation

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22
Q

What 3 systems are happening simultaneously?

A
  1. Neural stem cells
  2. Hemangioblasts
  3. Microglial progenitors
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23
Q

what does microglial progenitors generate?

A

Microglial cells

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24
Q

What is the first key process that starts?

A

Neurogenesis

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25
Q

What does the mammalian cortex comprise?

A

6 layers, or laminae, each containing neurons with similar morphology, functional properties, connections and time and place of origin

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26
Q

What is a remarkable feature of the neocortex?

A

Inside-out arrangement of projection neurons

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27
Q

What is the inside-out arrangement of projection neurons?

A

The oldest neurons closest and youngest neurons farthest from their birth place near the ventricle 2,3,4,5,6

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28
Q

The layers of the neocortex are what?

A

conventionally numbers from the top

  1. layers II/III contain the youngest neurons
  2. layer VI the oldest
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29
Q

What does the inside-out layering mean?

A

each neuronal precursor has to migrate outward from the ventricle, pass beyond its predecessors and then stop, undergo terminal differentiation and establish its synaptic connections

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30
Q

What is the region where migration stops and is defined by a layer of specialised pioneer neurons called?

A
  1. Cajal-Retzius (CR) cells
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31
Q

What is the first-migrating layer of neurons called?

A

Subplate (SP)

whereas the next layers (VI, V, IV, etc. in order from bottom to top) stack up on top of them

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32
Q

Key human brain development timeline

A

Medulla, pons & spinal cord at 3 weeks gestation
• Cerebellum, hypothalamus & midbrain at 4 weeks gestation
• Cortex & hippocampus at ~7 weeks gestation

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33
Q

What does Reelin act as?

A

‘detach and stop’ signal for neurons

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34
Q

How do many neuronal precursors migrate by?

A

Locomotion

Crawling along the processes of cells known as radial glia, which span the cortical walls

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35
Q

What does radial glia serve as ?

A

Dual purpose as progenitor cells and as guide for locomotion of neuronal precursors

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36
Q

What does radial glia have?

A

Long processes that extend from cell body near the ventricles to the basement membrane at the pial surface of brain

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37
Q

What occurs in the detach and stop model?

A

Reelin induces detachment which causes neurons to stop migrating, thus explaining inside-out cortical layering

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38
Q

What does the mature brain have?

A

6 cortical layers

the embryonic structures disappear

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39
Q

What underlies the directional flow of information transfer in the central nervous system?

A

The ability of neurons to form a single axon and multiple dendrites

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40
Q

What are dendrites and axons?

A

molecularly and functionally distinct domains

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41
Q

What does dendrite integrate?

A
  1. synaptic input
  2. Triggering the generation of action potentials at the level of soma
  3. Action potential then propagate along axon which makes presynaptic contact onto target cell
42
Q

What can neurons do?

A

Polarise to form a single axon, multiple dendrites and later establish functional synaptic contact in reductionist in vitro conditions

43
Q

What is the process of axon-dendrite polarity?

A
  1. Radial cells connect to pial surface and ventricle
  2. Neuronal precursors attach onto radial cells
  3. Multiple neurite formation
  4. One major neurite becomes the leading process (LP) leaving behind a trailing process (TP)
  5. Radial translocation and axon elongate tangentially
  6. Cell body continues to translocate and axon continues to elongate
  7. LP becomes the apical dendrite and form local branching and axon continues to elongate to another neuron or effector cell
44
Q

What are neurons?

A
  1. Highly polarised

2. Spatial differences in shape, structure, and function within a cell

45
Q

What does astrocytes have?

A

Most form of glial cells

46
Q

What are astrocytes?

A

Subset of glia which are the most abundant cells in the mammalian CNS and plays numerous roles in the developing CNS

47
Q

What are the functions of Astrocytes

A
  1. Neuronal survival
  2. Programmed cell death
  3. Axonal + synaptic pruning
  4. Neuro/gliogenesis
  5. Postnatal angiogenesis and barriergenesis
  6. axonal guidance
  7. Postnatal synaptogenesis
48
Q

Neuronal survival

A
  1. Clearance of extracellular glutamate and ROS

2. Secretion of various neurotrophic molecules

49
Q

Programmed cell death

A

Induction of cell death in postnatal hippocampal neurons

50
Q

Axonal and synaptic pruning

A

Phagocytosis via MEGF10 and MERTK pathway

51
Q

Neuro/gliogenesis

A

Connection and communication with radial glial cells

52
Q

Postnatal angiogenesis and barriergenesis

A

Secretion of angiogenic factors and axonal guidance molecules

53
Q

Axonal guidance

A

Expression of extracellular matrix proteins and axonal guidance molecules

54
Q

postnatal synaptogenesis

A

secretion of synaptogenic molecules

e.g. TSPs and hevin

55
Q

What is the role of astrocytes?

A

Can produce nitric oxide - regulate the developmental switch from neuro- to astrogenesis and astroglial maturation

56
Q

What can microglia influence?

A

Adult hippocampal neurogenesis by phagocytosis of apoptotic cells

57
Q

Where all macroglia (astrocytes and oligodendrocytes)

A

Generated from neural stem cells in the ventricular zone and subventricular zone, the walls of the embryonic neural tube

58
Q

When does astrogenesis begin?

A

After neurogenesis and peaks in various rodent CNS regions during the late prenatal to early postnatal stages

59
Q

What are oligodendrocytes?

A

Glial cells that produce myelin (lipid-enriched-axon-sheathing membrane) essential for saltatory conduction of action potentials in CNS

60
Q

Where are oligodendrocytes progenitor cells produced?

A

Ventrally under the influence of morphogen sonic hedgehog (shh)

61
Q

What are oligodendrocytes

A

Last cell type to generate after neurons and astrocytes during development

62
Q

In mouse, where does 3 waves of oligodendrocytes production occur?

A

Under temporal and location restriction

63
Q

What happens at E12.5?

A

Nkx2.1 expressing OPC originate from the medial ganglionic eminence and entopeduncular area

64
Q

At E15.5

A

Gsh2/Gsx2 expressing OPC originate from the ganglionic eminences

65
Q

at P0

A

Emx1 expressing OPC originate from dorsal ventricular zone

66
Q

By PD10

A

all the NKx2.1 OPC disappear

67
Q

What does oligodendrocytes progenitor cells have?

A
  1. Great migration capacity

2. as from restricted sites can fill brain and spinal cord to generate oligodendrocytes and myelinate the entire CNS

68
Q

Oligodendrocytes

A

Stage III
- Neural stem cells

Specific markers Nestin GFAP

69
Q

Oliogendrocytes stage IV

A

Glial precursor cells

Specific markers:
Nestin, GFAP, NG2

70
Q

Oligodendrocytes stage V

A

Oligodendrocyte precursor cells

Specific markers:

  1. PDGFRA
  2. NGS
  3. SOX 10
  4. OLIG 2
71
Q

Stage VI

A

pre-oligodendroctues [O4]

Myelinating oligodendrocytes [MBP]

72
Q

What is model of myelination?

A
  1. oligodendrocytes extend and retract cellular processes until axon contacts made
  2. Axioglial communication occurs when the growth cone contacts axon
  3. The inner tongue pushes under the outer tongue to generate compact myelin
  4. Lateral expansion of myelin towards the nodes along axon for elongation of myelin sheath
  5. Cytoplasmoc channels allow for communication between inner and outer tongue
  6. Myelination stop when appropriate number of myelin wraps is achieved
73
Q

What is myelination in neurodevelopment?

A

Spatiotemporal pattern beginning in the cerebellum, pons and internal capsule (from birth)

  1. proceed caudocranially (between head and tail) from splenium (back) of corpus callosum and optic radiation (at 3 -4 months)
  2. To occpital and parietal lobe (4-6 months)
  3. To Genu (knee) of corpus callosum and frontal and temporal lobes (6-8 months)
74
Q

What does human MRI studies show?

A

White matter volume increases up to 10 years and exercising complex skills (e.g. playing piano) can further increase myelination

75
Q

Where does microglia originate from?

A

Myeloid precursors in embryonic yolk sac

76
Q

What are microglia maintained independently of?

A

Definitive haematopoiesis (blood related)

77
Q

What are microglia?

A

Developmentally distinct population of cells

although very similar to monocyte/macrophages

78
Q

What are microglial cells?

A

Resident macrophages that are important for CNS development, maintenance, response to injury, repair

79
Q

What does microglia have bigger roles in?

A
  1. Guiding of sprouting vessels
  2. Finding neurotrophic factors for neurons
  3. Induce apoptosis
  4. Synaptic pruning
  • Microglia modulate wiring and patterning in the developing CNS by regulating apoptosis of neuronal subpopulations
  • Releasing neurotrophic factors, and guiding sprouting vessels in the parenchyma
  • Important for circuit formation and maturation of neuronal networks
  • Regulating adult neurogenesis and maintaining neuronal health in the adult CNS
80
Q

What does microglia engulf?

A

Pre- and post-synaptic element (e.g. axonal terminals and dendritic spine)

81
Q

What does microglia use?

A

‘find-me’ signal
‘eat-,me’ signal
to undergo synaptic pruning
complement components iq and c3

82
Q

What does microglia rely on?

A

signals

83
Q

How does synaptogenesis during birth occur?

A

Rapidly, especially in the cerebral cortex where neurons send multiple branches of axons and dendrites and form excessive neural connections with other neurons

84
Q

What is synaptic pruning?

A

Refers to process by which extra neurons and synaptic connections are eliminated to increase in efficiency of neuronal transmission

85
Q

When does neurogenesis and synaptogenesis peak around?

A

2 years (~15,000 synapses per neuron)

86
Q

What does synaptic pruning by microglia remove?

A

Weak/redundant synaptic connections to make the brain more efficient

87
Q

What unique physiological process does the developing immature brain process?

A
  1. Increased excitation

2. Decreased inhibtion

88
Q

Where are the glutamate receptor (GluRs) developmentally regulated in?

A

Neurons and glia

89
Q

At birth, what does neuronal NMDARs have?

A
  1. High NR2B subunit levels
    = prolonged current decay times and excitatory postsynaptic potential
  2. High NR3A and NR2D subunit
    = Reduce sensitivity of NDMARs to magnesium ions (external magnesium ions block NMDAR channel)
90
Q

Decrease inhibition in immature brain

A

GABA is inhibitory in adult but is excitatory in immature neurons in all animal species

91
Q

What does GABA act on?

A
  1. GABA A (ionotropic)

2. GABA B (metabotropic) receptors

92
Q

What are the 2 major Cl- co-transporters?

A
  1. NKCC1

2. KCC2

93
Q

Decrease inhibition in immature brain, in adult

A

KCC2 export cl- is active and NKCC1 import cl- less active, so low intracellular cl- during resting, when GABA A receptor is activated, cl- will enter and cause hyperpolarisation

94
Q

In immature

A

the KCC2 export cl- is less active and NKCC1 import cl- is more active, so high intracellular cl- during resting
When GABA B receptor activated, cl- will leave and cause depolarisation

95
Q

Vasculogenesis

A
  1. Embryonic mesoderm give rise to blood cells and blood vessels
  2. Mesoderm cells differentiate into hemangioblast to form primitive blood island
  3. Hemangioblast differentiate into angioblast
  4. Endothelial cells form tubular structure for primary capillary plexus
  5. Remodelling of the vascular plexus by vasculogenesis form larger blood vessels
96
Q

What does Neovascularisation process of blood vessels occur?

A

Pre-existing blood vessels

97
Q

How are new blood capillary formed?

A

Sprouting of endothelial cell from existing wall

98
Q

What can happen to endothelial cells in adult?

A

Divide and move to site of injury for repair

99
Q

What is Rice-Vannucci rat model?

A

Unilateral left common carotid artery ligation

stop blood flow to one part of brain

put it in low oxygen (8%)

100
Q

Immature rat TBI model (Adelson model)

A
  1. post-natal day 17 Sprague-Dawley rats (3-45g)
  2. Dental cement a metal disk onto top of skull
    (avoid skill fracture and brain laceration)
  3. Drop 25 or 50g weight from 2 metres height
  4. From this study – u have neurotic areas and have ventriculomegaly
  5. Get edema and site bleeding
101
Q

Which blood vessel is ligated in the rice-vannuci rat HIE MODEL

A

Common Carotide artery

Brain PD (15 decks)

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