Lectures 1-6 Flashcards
1
Q
What is gastrulation
A
The process in which an embryo transforms from a single layer of cells into three layers of cells referred to as germ layers.
2
Q
The 3 germ layers
A
ectoderm, mesoderm, endoderm
3
Q
Neurulation
A
The process in which a subset of cells within the ectoderm differentiate into precursor cells that form the neural plate.
4
Q
The neural tube is formed at the:
A
Midline
5
Q
The neural tube consists of:
A
Stem cells, the floorplate, the roofplate, and the neural crest
6
Q
What are somites?
A
Precursors of axial musculature and skeleton
7
Q
After what formation does the mesoderm form somites?
A
After formation of the neural tube
8
Q
Where is the neural tube formed?
A
At the midline
9
Q
What induces neural induction?
A
Signaling factors from the roofplate, floorplate, notochord, somites, neuroectoderm.
10
Q
Where can you find neural precursor cells and radial glial cells?
A
In the neural tube
11
Q
Describe how postmitotic neuroblasts are formed from precursor cells
A
- Mitosis
- Asymmetric division
12
Q
What drives cellular differentiation of neural stem cells?
A
Retinoic acid
13
Q
Retinoic acid is released by:
A
All inductive structures (Roofplate, notochord, floorplate)
14
Q
Vitamin A:
A
Can cause birth defects due to neural tube malformation.
- In excess or deficiency
15
Q
How many ligands compose BMPs?
A
6
16
Q
FGFs:
A
Fibroblast growth factors
17
Q
BMPs:
A
Bone morphogenic proteins
18
Q
TGF:
A
Transforming growth factor
19
Q
What do FGFs do?
A
Secreted into extracellular matrix and bind to receptor tyrosine kinases to activate ras-MAP kinase pathway.
- FGF8 is important for forebrain and midbrain development.
20
Q
What are BMPs important for?
A
- Differentiation of the dorsal spinal cord, and initial induction of the neural ectoderm.
21
Q
BMPs act on:
A
Receptor serine kinases that form a complex with SAMD
22
Q
BMPs are regulated by:
A
Noggin and chordin (Endogenous antagonists).
23
Q
What happens when BMPs bind to noggin and chordin?
A
They are prevented from binding receptors and neutralization continues.
24
Q
How many ligands in Wnts?
A
19
25
Wnts acts on:
Two distinct pathways: Non-canonical and canonical
26
Canonical pathway leads to:
Activation of frizzled receptor and stabilization of beta-catenin, which translocates to the nucleus and interacts with TFs to induce gene expression.
27
Non-canonical pathway regulates:
Cell movements and fate leading to the lengthening of the neural plate and tube via activation of Frizzled and changes to intracellular calcium and protein kinase C
- Can also lead to activation of Jun kinase (JNK) which regulates cell shape and polarity
28
Shh acts on:
2 surface receptors: Patched and Smoothened
29
Shh is important for:
Closure of the neural tube and driving differentiation of neurons within the ventral neural tube.
30
When is Shh highly expressed?
In the notochord and floorplate during early embryogenesis
31
Why do we need gradient signals during spinal cord development?
- Signals can act to induce or inhibit gene expression by direct or indirect signaling
- Can drive progenitor gene expression and post-mitotic gene expression
32
Stem cell biology has recently advanced with respect to?
Maintaining pluripotency of embryonic stem cells in vivo and in vitro
33
Delta and Notch signaling involves:
Interaction between transmembrane ligands (Delta) and surface receptors (Notch)
-Must occur between neighbouring cells
34
What happens after Delta and Notch bind?
The Notch Intracellular Domain (NICD) is cleaved and translocates to the nucleus
35
Delta Notch signaling can lead to:
The downregulation of Delta in some cells (which remain as neural stem cells) and upregulation in others (which become neurons)
36
What are macroglia
astrocytes and oligodendrocytes
37
Macroglia are derived from:
Radial glial cells
38
Schwann cells are:
Neural crest cells that migrate further away from the ectoderm layer, give rise to sensory and autonomic neurons, and glial cells.
39
Development of Schwann cells:
- NCCs form Schwann cell precursors
- SCPs generate immature Schwann cells
- Immature SCs form myelinating or non-myelinating cells that ensheath large and small axons.
40
Myelination:
Provides an insulating sheath on neurons to enable saltatory conduction
41
___ myelinates axons within the PNS
Schwann cells
42
___ myelinates axons within the CNS
Oligodendrocytes
43
Myelin has a high proportion of ____ and a low proportion of ____
Lipid, protein
44
What makes myelin a good electrical insulator?
High proportion of lipids, making them less permeable to ions
45
Guillan-Barre Syndrome
- Inflammatory disorder of the PNS
- Afflicts any age
- Progression over days to weeks
- 80-90% recover with no lasting effects
- Spontaneous recovery every 2-3 weeks
46
Myelination follows 4 stages:
1. Schwann cells surround axon
2. Membrane fusion of the plasma membrane in one area
3. Layers beginning to form due to Schwann cell cytoplasm rotation
4. Layers compact to form a mature sheath and the cytoplasm is squeezed to the outside
47
A double membrane that spirals around the axon
Mesaxon
48
What is the origin of the myelin sheath
Inner mesaxon (IM)
49
The double membrane of the mesaxon is formed by:
The apposition of external surfaces that form the major dense line (MDL) and internal surfaces that form the intraperiod line (IPL).
50
Compaction of myelin sheath occurs by:
Direct interactions between extracellular P0 proteins on opposing external membranes
51
Compact myelin occurs where?
segmentally between the Nodes of Ranvier at the internode
52
The edges of myelin layers contain:
cytoplasm filled channels that spiral around the paranodal junction of the axon.
53
Purpose of the myelin layers
Provide a physical and electrical barrier between voltage-gates Na+ channels in the juxtaparanode
54
Differences in CNS myelination
- number and diameter of axons myelinated
- myelin proteins involved in compaction
55
Non-myelinating Schwann cells (NMSCs)
Arise from Schwann cell precursors and retain the capacity to myelinate.
56
Remak cells:
NMSCs that ensheath small diameter peripheral axons
57
Teloglial cells:
NMSCs that support pre-synaptic terminals at neuromuscular junctions
58
Axons within a Remak bundle have their own:
Mesaxon
59
Use of NMSCs:
Provide growth and survival factors to axons and are essential for normal PNS development and function
60
Satellite glial cells (SGCs):
Wrap around neuronal cell bodies within the PNS
61
How do SGCs connect to other SGCs
via gap junctions, adherens, and tight junctions
62
Cell types within the CNS:
- Ependymal cells
- Astrocytes
- Neurons
- Microglia
- Myelinating cell
63
Schwann Cell vs. Oligodendrocyte (Sheathing and myelinating)
Schwann cell forms one myelin sheath and myelinates one section of axon
Oligodendrocyte forms several myelin sheaths and myelinates sections of several axons
64
Two classifications of astrocytes:
Fibrous (white matter)
Protoplasmic (grey matter)
65
Makes up 50% of cells in the brain:
Astrocytes
66
Fibrous astrocytes:
Arranged in rows between axon bundles
67
Astrocytes help to support myelination in CNS by:
- Aligning oligodendrocyte processes with axons
- Releasing gliotrophic factors that promote oligodendrocyte survival
- Increasing the rate of myelin wrapping in response to electrical activity
68
What are protoplasmic astrocytes
Astrocytes which have fine processes that cover all areas of grey matter, including dendrites, axons, synapses and vasculature
69
Astrocytes' roles within the CNS
1. Maintaining physiological homeostasis of CNS
- K+ buffering and pH balancing
- Re-cycling of neurotransmitters
- Alternative energy source
- Production of anti-oxidants
2. Formation and support of synaptic processes
3. Maintenance and formation of the BBB
70
Astrocytes roles in pH buffering:
- Carbonic anhydrase (CA) in astrocytes converts CO2 to HCO3- and H+
- HCO3- is released and can buffer the H+ from neurons
71
Astrocytes roles in glutamate-glutamine cycle
- Astrocytes remove glutamate from synaptic cleft
- Glutamine synthase converts it into glutamine
- Glutaminase converts glutamine into glutamate
72
Astrocytes role in the lactate shuttle
- Lactate is shuttled to neurons via astrocytes as alternative energy substrate
73
Astrocytes role in K+ buffering
Excess K+ removed to lower concentration gradient
74
Astrocytes role in antioxidant production
- Astrocytes produce/release glutathione (GSH) and precursor
- Precursor (CysGly) taken in by neurons to produce GSH
- GSH binds reactive oxygen species caused by neuronal activity.
75
How do astrocytes maintain the BBB?
They regulate cerebral blood flow and the permeability of the BBB
76
Ependymal cells are derived from:
Neural precursors
77
What are ependymal cells
Form a single layer of ciliated cells that help to circulate cerebral spinal fluid throughout the ventricular system
78
Where do microglial cells originate
The yolk sac and (later) bone marrow. DO NOT form from neuroectoderm
79
Function of microglia
Support many processes of the developing brain including neurogenesis and gliogenesis, differentiation, axonal synaptic pruning, and myelination
- Rapidly clear debris, proteins, toxins, or dying cells within the brain
- Release cytokines that have pro- or -anti- inflammatory effects.
- First line of defense
80
Nerve-glial antigen 2 (NG2) cells are important for:
Maintaining a constant glial precursor population within CNS and has a distinct contact with neurons
81
Treatment options for CNS injury (SCI)
Very limited, often resulting in permanent and extensive deficits of sensory, motor, and autonomic function
82
Boundary cap cells (BCCs) form:
Several cell types, as they are multipotent
- Neurons
- Glia
- Smooth muscle cells
83
Where are BCCs located?
At the entry point for sensory neurons, and exit point for motor axons
84
BCC function:
Regulate growth of sensory axons into the CNS and prevent motor neurons and central glial neurons to exit the CNS during development.
85
Characteristics of CNS regeneration:
- Extremely limited
- Axonal regrowth largely fails and glia inhibit axon growth
86
Characteristics of PNS regeneration:
- 1mm/day
- Neurons can sprout collaterals and regenerate
- Glia produce growth factors
- Macrophages remove debris
87
If peripheral nerve regeneration is not successful, :
Results in permanent loss of function
88
Describe successful nerve regeneration following PNS injury
- The distal axon degenerates, referred to as Wallerian degeneration. The axon degenerates up to the first node closest to injury site
- The denervated muscle begins to atrophy
- Infiltrating macrophages clean dead cells and debris within the nerve
- Schwann cells proliferate around the distal axon and form bands within the injury site (bands of Bungner). They release neurotrophic factors that promote axonal regrowth
89
Henry Head
Famously severed his own radial nerve.
- 6 weeks: return of pressure and touch
- 2-6 months: Regained pain, temperature, light touch sensations.
- 2 years: Not all proprioception or mechanoreception has returned
90
Surgical re-apposition of a damaged nerve:
Neural tubes assist in creation of bands of Bungner, contain immune cells, and an array of ECM that help guide axons
91
Mammal's regenerative abilities:
Limited to no regenerative capabilities
92
Death of oligodendrocytes following axonal injury in the CNS:
Leads to expansion of injury site
93
More successful PNS regeneration if:
The perineurium or epineurium is intact (crush vs cut)
94
Following CNS axonal injury...:
- The distal axon degenerates and demyelinates
- Microglia become reactive
- Astrocytes also become reactive and migrate to the injury site
- Astrocytes form a barrier around the injury site known as the boundary of the glial scar.
95
Following local damage in the CNS, astrocytes and microglia...:
Release damage-associate molecular patterns (DAMP), cytokines, and chemokines that further activate and attract glial cells
96
Importance of the glial scar:
To create a physical and chemical barrier to axonal regeneration
97
Edema in the injury site of the CNS occurs when...:
Blood vessels are damaged
98
Oligodendrocytes express ____ that inhibit axon growth when they interact with their receptors:
Myelin proteins i.e. Nogo-A
99
Where is the dura mater:
Firmly attached to the skull
100
Where is the pia mater:
Covers surface of brain
101
Where is the arachnoid mater:
Lines inner surface of dura
102
Meningeal layers of brain, from outside to inside:
Scalp, skull, periosteal dura mater, meningeal dura mater, arachnoid mater, subarachnoid space, pia mater, cerebral cortex
103
Inward extensions of dura divide the cranium into compartments, what are those compartments?
Falx cerebri: In between left and right cerebral hemispheres
Tentorium cerebelli: In between cerebellum and cerebrum
104
Two types of meningeal arteries:
Between dura and skull, and from external carotid artery
105
Epidural hematoma:
Rupture of meningeal vessel
Blunt force to skull (blood between dura and skull)
106
Subdural hematoma:
Rupture of bridging vein
Sudden movement of head causes brain to move inside skull (Blood in CSF space)
107
Subarachnoid hematoma:
Rupture of cerebral artery
- Aneurysm- congenital weakening of artery wall (Blood in CSF space)
108
Meningitis:
- Infection of the lining of the brain caused primarily by bacterial infections
- Infiltration of immune cells into subarachnoid space
109
Spinal cord meninges, outside to inside:
Dura mater, arachnoid mater, pia mater, subarachnoid space filled with CSF
110
Epidural is placed...
In the epidural fat space within the dura mater
111
Spinal taps are placed...
In the arachnoid mater
112
CSF is produced by:
choroid plexus in the 4th, 3rd, and lateral ventricles
113
CSF provides:
nutrients, hormones, and metabolites.
- also provides buoyancy and protection
114
What circulates CSF:
Hydrostatic pressure from constant production, beating ependymal cilia and arterial pulsations
115
CSF drains from ___ to ____:
Subarachnoid space, the superior sagittal sinus
116
CSF flows from ____, through ____, to ____:
Lateral ventricles, through intraventricular foramina, to 3rd ventricle
117
Leakage from ventricular system to subarachnoid space occurs through:
Foramina in the 4th ventricle
118
CSF drainage:
Occurs from the subarachnoid space into the superior sagittal sinus and to a lesser extent, the cerebral lymphatic system
119
CSF and waste damage:
What drains CSF, blood, and wastes?
Dural sinuses and lymphatics
120
CSF composition:
1. Filtered plasma
- sodium
-chloride
- potassium, calcium
- proteins
-glucose
2. Very few white blood cells
3. No red blood cells
121
85% of aneurysms occur...
In the CoW
122
Anterior cerebral artery supplies blood to...
The anterior and medial aspects of the frontal and parietal lobes
123
Middle cerebral artery supplies blood to...
The lateral and deep nuclei of the frontal, parietal, and temporal lobes
124
Posterior cerebral artery supplies blood to...
The occipital lobe and lower temporal lobe
125
Functional deficits due to strokes depend on...
The area of the brain supplied by the affected artery
126
Functional deficits due to strokes in the frontal lobe:
Emotions, personality, motor, problem-solving, reasoning
127
Functional deficits due to strokes in the temporal lobe:
Language, hearing, speech
128
Functional deficits due to strokes in the occipital lobe:
Vision
129
Functional deficits due to strokes in the parietal lobe:
Sensory
130
Functional deficits due to strokes in the cerebellum:
Balance and coordination
131
Functional deficits due to strokes in the brainstem:
Basic body functions
132
Deep cerebral arteries include:
Anterior, middle, and posterior cerebral arteries
133
What is a hemorrhagic stroke:
Hemorrhage/blood leaks into brain tissue
134
Ischemic stroke:
Clot stops blood supply to an area of the brain
135
Internal jugular veins lead:
To SVC and heart
136
Arterior spinal artery runs along ____ and infuses ____
The ventral side of the spinal cord, infuses lower 2/3s of cord
137
Posterior spinal arteries provide blood to:
Top 1/3 of spinal cord
138
BBB permeability changes...
With age
139
Direction of gas exchange within the BBB
Oxygen flows out of the blood into the brain, CO2 flows oppositely
140
What creates the first barrier between blood and CNS tissue?
- Claudins and occludins
The endothelial cells of the capillary possess tight junctions and adhesion molecules
141
What occurs during endothelial shrinkage in age-related BBB breakdown?
Decreased expression of tight junction proteins
142
Only molecules capable of passing through the BBB passively:
small lipophilic molecules
143
Pericytes are important for _____ (concerning the BBB)
Structural support, expression of tight junction proteins, formation of the basal lamina, and regulating blood flow
144
Homeostatic roles of the BBB
- Maintain ionic homeostasis via ion channels
- Carrier-mediated transport for nutrients
- Receptor-mediated transport for larger molecules
- Protect the brain against toxins
145
The final barrier of the BBB is comprised of:
astrocytes
146
The blood-nerve barrier consists of:
Endoneurial microvessels, basement membrane, pericytes, and the perineurium
147
Pericyte's roles in the PNS
Help support endothelial cells
148
Schwann cell's role in the PNS barrier
Form a myelin barrier also held together by tight junctions
149
Blood-Nerve Barrier
Consists of specialized endothelial cells and is important for maintaining the health and function of peripheral nerves
