Week 4 part 1 Flashcards
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
2
Q
When is the male brain weight heavier than female (~10%)?
A
From 2 years onwards
3
Q
How old is the brain when the child is born?
A
8 months
4
Q
What is the brain growth and differentiation controlled mainly by?
A
Genes
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
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
7
Q
When does the brain get smaller?
A
20 years old
8
Q
What is neurulation?
A
Formation of neural tube
9
Q
What is the process of neurulation?
A
- Neural plate is formed from the thickening of the dorsal ectoderm
- Nueral groove with neural fold either side occur at midline of neural plate along notochord
- Neural plate fold to form the neural tube
- Neurulation proceed bidirectionally from mid portion to cranial and caudal ends
- Thickening of the neural tube wall forms the brain and spinal cord. the lumen of the tube forms the ventral and central canal
- Neuroepithelial cells forming neural tube wall give rise to neurons and macroglia (astrocytes, oligodendrocytes, ependymal cells)
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
11
Q
What can Glia be classified as?
A
Different subsets, based on their morphology, function and location in the nervous system
12
Q
What are the 2 main glial subset in CNS?
A
- Microglia
- Including astrocytes and oligodendrocytes
- macroglia
13
Q
What does glia have?
A
- ‘yolk sac’ macrophage based source, from where they colonize the brain during prenatal development
14
Q
Where are microglia derived from?
A
Neural lineage
Produced after initial neuronal birth wave o
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.
16
Q
What are all from the neural stem cells?
A
- Neurons
- Astrocytes
- Oligodendrocytes
17
Q
What can neural stem cells split into?
A
- Neuronal progenitor (becomes neurons)
2. Glial progenitor (which becomes astrocytes/oligo’s)
18
Q
What does neuron give rise to?
A
Majority of the brain cells
19
Q
Where is blood supply from?
A
Mesoderm formation
Has Hemangioblasts
20
Q
What are hemangioblast?
A
Multipotent precursor cells that can differentiate into both hematopoietic and endothelial cells
21
Q
What is hematopoietic cells surrounded by?
A
Endothelial cells
Part of blood vessels and they form capillary plexus in terms of orientation
22
Q
What 3 systems are happening simultaneously?
A
- Neural stem cells
- Hemangioblasts
- Microglial progenitors
23
Q
what does microglial progenitors generate?
A
Microglial cells
24
Q
What is the first key process that starts?
A
Neurogenesis
25
What does the mammalian cortex comprise?
6 layers, or laminae, each containing neurons with similar morphology, functional properties, connections and time and place of origin
26
What is a remarkable feature of the neocortex?
Inside-out arrangement of projection neurons
27
What is the inside-out arrangement of projection neurons?
The oldest neurons closest and youngest neurons farthest from their birth place near the ventricle 2,3,4,5,6
28
The layers of the neocortex are what?
conventionally numbers from the top
1. layers II/III contain the youngest neurons
2. layer VI the oldest
29
What does the inside-out layering mean?
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
30
What is the region where migration stops and is defined by a layer of specialised pioneer neurons called?
1. Cajal-Retzius (CR) cells
31
What is the first-migrating layer of neurons called?
Subplate (SP)
| whereas the next layers (VI, V, IV, etc. in order from bottom to top) stack up on top of them
32
Key human brain development timeline
Medulla, pons & spinal cord at 3 weeks gestation
• Cerebellum, hypothalamus & midbrain at 4 weeks gestation
• Cortex & hippocampus at ~7 weeks gestation
33
What does Reelin act as?
'detach and stop' signal for neurons
34
How do many neuronal precursors migrate by?
Locomotion
Crawling along the processes of cells known as radial glia, which span the cortical walls
35
What does radial glia serve as ?
Dual purpose as progenitor cells and as guide for locomotion of neuronal precursors
36
What does radial glia have?
Long processes that extend from cell body near the ventricles to the basement membrane at the pial surface of brain
37
What occurs in the detach and stop model?
Reelin induces detachment which causes neurons to stop migrating, thus explaining inside-out cortical layering
38
What does the mature brain have?
6 cortical layers
| the embryonic structures disappear
39
What underlies the directional flow of information transfer in the central nervous system?
The ability of neurons to form a single axon and multiple dendrites
40
What are dendrites and axons?
molecularly and functionally distinct domains
41
What does dendrite integrate?
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
What can neurons do?
Polarise to form a single axon, multiple dendrites and later establish functional synaptic contact in reductionist in vitro conditions
43
What is the process of axon-dendrite polarity?
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
What are neurons?
1. Highly polarised
| 2. Spatial differences in shape, structure, and function within a cell
45
What does astrocytes have?
Most form of glial cells
46
What are astrocytes?
Subset of glia which are the most abundant cells in the mammalian CNS and plays numerous roles in the developing CNS
47
What are the functions of Astrocytes
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
Neuronal survival
1. Clearance of extracellular glutamate and ROS
| 2. Secretion of various neurotrophic molecules
49
Programmed cell death
Induction of cell death in postnatal hippocampal neurons
50
Axonal and synaptic pruning
Phagocytosis via MEGF10 and MERTK pathway
51
Neuro/gliogenesis
Connection and communication with radial glial cells
52
Postnatal angiogenesis and barriergenesis
Secretion of angiogenic factors and axonal guidance molecules
53
Axonal guidance
Expression of extracellular matrix proteins and axonal guidance molecules
54
postnatal synaptogenesis
secretion of synaptogenic molecules
| e.g. TSPs and hevin
55
What is the role of astrocytes?
Can produce nitric oxide - regulate the developmental switch from neuro- to astrogenesis and astroglial maturation
56
What can microglia influence?
Adult hippocampal neurogenesis by phagocytosis of apoptotic cells
57
Where all macroglia (astrocytes and oligodendrocytes)
Generated from neural stem cells in the ventricular zone and subventricular zone, the walls of the embryonic neural tube
58
When does astrogenesis begin?
After neurogenesis and peaks in various rodent CNS regions during the late prenatal to early postnatal stages
59
What are oligodendrocytes?
Glial cells that produce myelin (lipid-enriched-axon-sheathing membrane) essential for saltatory conduction of action potentials in CNS
60
Where are oligodendrocytes progenitor cells produced?
Ventrally under the influence of morphogen sonic hedgehog (shh)
61
What are oligodendrocytes
Last cell type to generate after neurons and astrocytes during development
62
In mouse, where does 3 waves of oligodendrocytes production occur?
Under temporal and location restriction
63
What happens at E12.5?
Nkx2.1 expressing OPC originate from the medial ganglionic eminence and entopeduncular area
64
At E15.5
Gsh2/Gsx2 expressing OPC originate from the ganglionic eminences
65
at P0
Emx1 expressing OPC originate from dorsal ventricular zone
66
By PD10
all the NKx2.1 OPC disappear
67
What does oligodendrocytes progenitor cells have?
1. Great migration capacity
| 2. as from restricted sites can fill brain and spinal cord to generate oligodendrocytes and myelinate the entire CNS
68
Oligodendrocytes
Stage III
- Neural stem cells
Specific markers Nestin GFAP
69
Oliogendrocytes stage IV
Glial precursor cells
Specific markers:
Nestin, GFAP, NG2
70
Oligodendrocytes stage V
Oligodendrocyte precursor cells
Specific markers:
1. PDGFRA
2. NGS
3. SOX 10
4. OLIG 2
71
Stage VI
pre-oligodendroctues [O4]
| Myelinating oligodendrocytes [MBP]
72
What is model of myelination?
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
What is myelination in neurodevelopment?
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
What does human MRI studies show?
White matter volume increases up to 10 years and exercising complex skills (e.g. playing piano) can further increase myelination
75
Where does microglia originate from?
Myeloid precursors in embryonic yolk sac
76
What are microglia maintained independently of?
Definitive haematopoiesis (blood related)
77
What are microglia?
Developmentally distinct population of cells
although very similar to monocyte/macrophages
78
What are microglial cells?
Resident macrophages that are important for CNS development, maintenance, response to injury, repair
79
What does microglia have bigger roles in?
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
What does microglia engulf?
Pre- and post-synaptic element (e.g. axonal terminals and dendritic spine)
81
What does microglia use?
'find-me' signal
'eat-,me' signal
to undergo synaptic pruning
complement components iq and c3
82
What does microglia rely on?
signals
83
How does synaptogenesis during birth occur?
Rapidly, especially in the cerebral cortex where neurons send multiple branches of axons and dendrites and form excessive neural connections with other neurons
84
What is synaptic pruning?
Refers to process by which extra neurons and synaptic connections are eliminated to increase in efficiency of neuronal transmission
85
When does neurogenesis and synaptogenesis peak around?
2 years (~15,000 synapses per neuron)
86
What does synaptic pruning by microglia remove?
Weak/redundant synaptic connections to make the brain more efficient
87
What unique physiological process does the developing immature brain process?
1. Increased excitation
| 2. Decreased inhibtion
88
Where are the glutamate receptor (GluRs) developmentally regulated in?
Neurons and glia
89
At birth, what does neuronal NMDARs have?
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
Decrease inhibition in immature brain
GABA is inhibitory in adult but is excitatory in immature neurons in all animal species
91
What does GABA act on?
1. GABA A (ionotropic)
| 2. GABA B (metabotropic) receptors
92
What are the 2 major Cl- co-transporters?
1. NKCC1
| 2. KCC2
93
Decrease inhibition in immature brain, in adult
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
In immature
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
Vasculogenesis
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
What does Neovascularisation process of blood vessels occur?
Pre-existing blood vessels
97
How are new blood capillary formed?
Sprouting of endothelial cell from existing wall
98
What can happen to endothelial cells in adult?
Divide and move to site of injury for repair
99
What is Rice-Vannucci rat model?
Unilateral left common carotid artery ligation
stop blood flow to one part of brain
put it in low oxygen (8%)
100
Immature rat TBI model (Adelson model)
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
Which blood vessel is ligated in the rice-vannuci rat HIE MODEL
Common Carotide artery
