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NEUR*2100 > Lectures 1-6 > Flashcards

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.

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2
Q

The 3 germ layers

A

ectoderm, mesoderm, endoderm

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3
Q

Neurulation

A

The process in which a subset of cells within the ectoderm differentiate into precursor cells that form the neural plate.

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4
Q

The neural tube is formed at the:

A

Midline

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5
Q

The neural tube consists of:

A

Stem cells, the floorplate, the roofplate, and the neural crest

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6
Q

What are somites?

A

Precursors of axial musculature and skeleton

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7
Q

After what formation does the mesoderm form somites?

A

After formation of the neural tube

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8
Q

Where is the neural tube formed?

A

At the midline

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9
Q

What induces neural induction?

A

Signaling factors from the roofplate, floorplate, notochord, somites, neuroectoderm.

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10
Q

Where can you find neural precursor cells and radial glial cells?

A

In the neural tube

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11
Q

Describe how postmitotic neuroblasts are formed from precursor cells

A
  • Mitosis
  • Asymmetric division
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12
Q

What drives cellular differentiation of neural stem cells?

A

Retinoic acid

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13
Q

Retinoic acid is released by:

A

All inductive structures (Roofplate, notochord, floorplate)

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14
Q

Vitamin A:

A

Can cause birth defects due to neural tube malformation.
- In excess or deficiency

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15
Q

How many ligands compose BMPs?

A

6

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16
Q

FGFs:

A

Fibroblast growth factors

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17
Q

BMPs:

A

Bone morphogenic proteins

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18
Q

TGF:

A

Transforming growth factor

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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.
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20
Q

What are BMPs important for?

A
  • Differentiation of the dorsal spinal cord, and initial induction of the neural ectoderm.
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21
Q

BMPs act on:

A

Receptor serine kinases that form a complex with SAMD

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22
Q

BMPs are regulated by:

A

Noggin and chordin (Endogenous antagonists).

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23
Q

What happens when BMPs bind to noggin and chordin?

A

They are prevented from binding receptors and neutralization continues.

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24
Q

How many ligands in Wnts?

A

19

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25
Q

Wnts acts on:

A

Two distinct pathways: Non-canonical and canonical

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26
Q

Canonical pathway leads to:

A

Activation of frizzled receptor and stabilization of beta-catenin, which translocates to the nucleus and interacts with TFs to induce gene expression.

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27
Q

Non-canonical pathway regulates:

A

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

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28
Q

Shh acts on:

A

2 surface receptors: Patched and Smoothened

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29
Q

Shh is important for:

A

Closure of the neural tube and driving differentiation of neurons within the ventral neural tube.

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30
Q

When is Shh highly expressed?

A

In the notochord and floorplate during early embryogenesis

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31
Q

Why do we need gradient signals during spinal cord development?

A
  • Signals can act to induce or inhibit gene expression by direct or indirect signaling
  • Can drive progenitor gene expression and post-mitotic gene expression
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32
Q

Stem cell biology has recently advanced with respect to?

A

Maintaining pluripotency of embryonic stem cells in vivo and in vitro

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33
Q

Delta and Notch signaling involves:

A

Interaction between transmembrane ligands (Delta) and surface receptors (Notch)
-Must occur between neighbouring cells

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34
Q

What happens after Delta and Notch bind?

A

The Notch Intracellular Domain (NICD) is cleaved and translocates to the nucleus

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35
Q

Delta Notch signaling can lead to:

A

The downregulation of Delta in some cells (which remain as neural stem cells) and upregulation in others (which become neurons)

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36
Q

What are macroglia

A

astrocytes and oligodendrocytes

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37
Q

Macroglia are derived from:

A

Radial glial cells

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38
Q

Schwann cells are:

A

Neural crest cells that migrate further away from the ectoderm layer, give rise to sensory and autonomic neurons, and glial cells.

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39
Q

Development of Schwann cells:

A
  • NCCs form Schwann cell precursors
  • SCPs generate immature Schwann cells
  • Immature SCs form myelinating or non-myelinating cells that ensheath large and small axons.
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40
Q

Myelination:

A

Provides an insulating sheath on neurons to enable saltatory conduction

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41
Q

___ myelinates axons within the PNS

A

Schwann cells

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42
Q

___ myelinates axons within the CNS

A

Oligodendrocytes

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43
Q

Myelin has a high proportion of ____ and a low proportion of ____

A

Lipid, protein

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44
Q

What makes myelin a good electrical insulator?

A

High proportion of lipids, making them less permeable to ions

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45
Q

Guillan-Barre Syndrome

A
  • 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
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46
Q

Myelination follows 4 stages:

A
  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
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47
Q

A double membrane that spirals around the axon

A

Mesaxon

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48
Q

What is the origin of the myelin sheath

A

Inner mesaxon (IM)

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49
Q

The double membrane of the mesaxon is formed by:

A

The apposition of external surfaces that form the major dense line (MDL) and internal surfaces that form the intraperiod line (IPL).

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50
Q

Compaction of myelin sheath occurs by:

A

Direct interactions between extracellular P0 proteins on opposing external membranes

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51
Q

Compact myelin occurs where?

A

segmentally between the Nodes of Ranvier at the internode

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52
Q

The edges of myelin layers contain:

A

cytoplasm filled channels that spiral around the paranodal junction of the axon.

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53
Q

Purpose of the myelin layers

A

Provide a physical and electrical barrier between voltage-gates Na+ channels in the juxtaparanode

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54
Q

Differences in CNS myelination

A
  • number and diameter of axons myelinated
  • myelin proteins involved in compaction
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55
Q

Non-myelinating Schwann cells (NMSCs)

A

Arise from Schwann cell precursors and retain the capacity to myelinate.

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56
Q

Remak cells:

A

NMSCs that ensheath small diameter peripheral axons

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57
Q

Teloglial cells:

A

NMSCs that support pre-synaptic terminals at neuromuscular junctions

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58
Q

Axons within a Remak bundle have their own:

A

Mesaxon

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59
Q

Use of NMSCs:

A

Provide growth and survival factors to axons and are essential for normal PNS development and function

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60
Q

Satellite glial cells (SGCs):

A

Wrap around neuronal cell bodies within the PNS

61
Q

How do SGCs connect to other SGCs

A

via gap junctions, adherens, and tight junctions

62
Q

Cell types within the CNS:

A
  • Ependymal cells
  • Astrocytes
  • Neurons
  • Microglia
  • Myelinating cell
63
Q

Schwann Cell vs. Oligodendrocyte (Sheathing and myelinating)

A

Schwann cell forms one myelin sheath and myelinates one section of axon
Oligodendrocyte forms several myelin sheaths and myelinates sections of several axons

64
Q

Two classifications of astrocytes:

A

Fibrous (white matter)
Protoplasmic (grey matter)

65
Q

Makes up 50% of cells in the brain:

A

Astrocytes

66
Q

Fibrous astrocytes:

A

Arranged in rows between axon bundles

67
Q

Astrocytes help to support myelination in CNS by:

A
  • Aligning oligodendrocyte processes with axons
  • Releasing gliotrophic factors that promote oligodendrocyte survival
  • Increasing the rate of myelin wrapping in response to electrical activity
68
Q

What are protoplasmic astrocytes

A

Astrocytes which have fine processes that cover all areas of grey matter, including dendrites, axons, synapses and vasculature

69
Q

Astrocytes’ roles within the CNS

A
  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
Q

Astrocytes roles in pH buffering:

A
  • Carbonic anhydrase (CA) in astrocytes converts CO2 to HCO3- and H+
  • HCO3- is released and can buffer the H+ from neurons
71
Q

Astrocytes roles in glutamate-glutamine cycle

A
  • Astrocytes remove glutamate from synaptic cleft
  • Glutamine synthase converts it into glutamine
  • Glutaminase converts glutamine into glutamate
72
Q

Astrocytes role in the lactate shuttle

A
  • Lactate is shuttled to neurons via astrocytes as alternative energy substrate
73
Q

Astrocytes role in K+ buffering

A

Excess K+ removed to lower concentration gradient

74
Q

Astrocytes role in antioxidant production

A
  • 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
Q

How do astrocytes maintain the BBB?

A

They regulate cerebral blood flow and the permeability of the BBB

76
Q

Ependymal cells are derived from:

A

Neural precursors

77
Q

What are ependymal cells

A

Form a single layer of ciliated cells that help to circulate cerebral spinal fluid throughout the ventricular system

78
Q

Where do microglial cells originate

A

The yolk sac and (later) bone marrow. DO NOT form from neuroectoderm

79
Q

Function of microglia

A

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
Q

Nerve-glial antigen 2 (NG2) cells are important for:

A

Maintaining a constant glial precursor population within CNS and has a distinct contact with neurons

81
Q

Treatment options for CNS injury (SCI)

A

Very limited, often resulting in permanent and extensive deficits of sensory, motor, and autonomic function

82
Q

Boundary cap cells (BCCs) form:

A

Several cell types, as they are multipotent
- Neurons
- Glia
- Smooth muscle cells

83
Q

Where are BCCs located?

A

At the entry point for sensory neurons, and exit point for motor axons

84
Q

BCC function:

A

Regulate growth of sensory axons into the CNS and prevent motor neurons and central glial neurons to exit the CNS during development.

85
Q

Characteristics of CNS regeneration:

A
  • Extremely limited
  • Axonal regrowth largely fails and glia inhibit axon growth
86
Q

Characteristics of PNS regeneration:

A
  • 1mm/day
  • Neurons can sprout collaterals and regenerate
  • Glia produce growth factors
  • Macrophages remove debris
87
Q

If peripheral nerve regeneration is not successful, :

A

Results in permanent loss of function

88
Q

Describe successful nerve regeneration following PNS injury

A
  • 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
Q

Henry Head

A

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
Q

Surgical re-apposition of a damaged nerve:

A

Neural tubes assist in creation of bands of Bungner, contain immune cells, and an array of ECM that help guide axons

91
Q

Mammal’s regenerative abilities:

A

Limited to no regenerative capabilities

92
Q

Death of oligodendrocytes following axonal injury in the CNS:

A

Leads to expansion of injury site

93
Q

More successful PNS regeneration if:

A

The perineurium or epineurium is intact (crush vs cut)

94
Q

Following CNS axonal injury…:

A
  • 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
Q

Following local damage in the CNS, astrocytes and microglia…:

A

Release damage-associate molecular patterns (DAMP), cytokines, and chemokines that further activate and attract glial cells

96
Q

Importance of the glial scar:

A

To create a physical and chemical barrier to axonal regeneration

97
Q

Edema in the injury site of the CNS occurs when…:

A

Blood vessels are damaged

98
Q

Oligodendrocytes express ____ that inhibit axon growth when they interact with their receptors:

A

Myelin proteins i.e. Nogo-A

99
Q

Where is the dura mater:

A

Firmly attached to the skull

100
Q

Where is the pia mater:

A

Covers surface of brain

101
Q

Where is the arachnoid mater:

A

Lines inner surface of dura

102
Q

Meningeal layers of brain, from outside to inside:

A

Scalp, skull, periosteal dura mater, meningeal dura mater, arachnoid mater, subarachnoid space, pia mater, cerebral cortex

103
Q

Inward extensions of dura divide the cranium into compartments, what are those compartments?

A

Falx cerebri: In between left and right cerebral hemispheres
Tentorium cerebelli: In between cerebellum and cerebrum

104
Q

Two types of meningeal arteries:

A

Between dura and skull, and from external carotid artery

105
Q

Epidural hematoma:

A

Rupture of meningeal vessel
Blunt force to skull (blood between dura and skull)

106
Q

Subdural hematoma:

A

Rupture of bridging vein
Sudden movement of head causes brain to move inside skull (Blood in CSF space)

107
Q

Subarachnoid hematoma:

A

Rupture of cerebral artery
- Aneurysm- congenital weakening of artery wall (Blood in CSF space)

108
Q

Meningitis:

A
  • Infection of the lining of the brain caused primarily by bacterial infections
  • Infiltration of immune cells into subarachnoid space
109
Q

Spinal cord meninges, outside to inside:

A

Dura mater, arachnoid mater, pia mater, subarachnoid space filled with CSF

110
Q

Epidural is placed…

A

In the epidural fat space within the dura mater

111
Q

Spinal taps are placed…

A

In the arachnoid mater

112
Q

CSF is produced by:

A

choroid plexus in the 4th, 3rd, and lateral ventricles

113
Q

CSF provides:

A

nutrients, hormones, and metabolites.
- also provides buoyancy and protection

114
Q

What circulates CSF:

A

Hydrostatic pressure from constant production, beating ependymal cilia and arterial pulsations

115
Q

CSF drains from ___ to ____:

A

Subarachnoid space, the superior sagittal sinus

116
Q

CSF flows from ____, through ____, to ____:

A

Lateral ventricles, through intraventricular foramina, to 3rd ventricle

117
Q

Leakage from ventricular system to subarachnoid space occurs through:

A

Foramina in the 4th ventricle

118
Q

CSF drainage:

A

Occurs from the subarachnoid space into the superior sagittal sinus and to a lesser extent, the cerebral lymphatic system

119
Q

CSF and waste damage:
What drains CSF, blood, and wastes?

A

Dural sinuses and lymphatics

120
Q

CSF composition:

A
  1. Filtered plasma
    - sodium
    -chloride
    - potassium, calcium
    - proteins
    -glucose
  2. Very few white blood cells
  3. No red blood cells
121
Q

85% of aneurysms occur…

A

In the CoW

122
Q

Anterior cerebral artery supplies blood to…

A

The anterior and medial aspects of the frontal and parietal lobes

123
Q

Middle cerebral artery supplies blood to…

A

The lateral and deep nuclei of the frontal, parietal, and temporal lobes

124
Q

Posterior cerebral artery supplies blood to…

A

The occipital lobe and lower temporal lobe

125
Q

Functional deficits due to strokes depend on…

A

The area of the brain supplied by the affected artery

126
Q

Functional deficits due to strokes in the frontal lobe:

A

Emotions, personality, motor, problem-solving, reasoning

127
Q

Functional deficits due to strokes in the temporal lobe:

A

Language, hearing, speech

128
Q

Functional deficits due to strokes in the occipital lobe:

A

Vision

129
Q

Functional deficits due to strokes in the parietal lobe:

A

Sensory

130
Q

Functional deficits due to strokes in the cerebellum:

A

Balance and coordination

131
Q

Functional deficits due to strokes in the brainstem:

A

Basic body functions

132
Q

Deep cerebral arteries include:

A

Anterior, middle, and posterior cerebral arteries

133
Q

What is a hemorrhagic stroke:

A

Hemorrhage/blood leaks into brain tissue

134
Q

Ischemic stroke:

A

Clot stops blood supply to an area of the brain

135
Q

Internal jugular veins lead:

A

To SVC and heart

136
Q

Arterior spinal artery runs along ____ and infuses ____

A

The ventral side of the spinal cord, infuses lower 2/3s of cord

137
Q

Posterior spinal arteries provide blood to:

A

Top 1/3 of spinal cord

138
Q

BBB permeability changes…

A

With age

139
Q

Direction of gas exchange within the BBB

A

Oxygen flows out of the blood into the brain, CO2 flows oppositely

140
Q

What creates the first barrier between blood and CNS tissue?

A
  • Claudins and occludins
    The endothelial cells of the capillary possess tight junctions and adhesion molecules
141
Q

What occurs during endothelial shrinkage in age-related BBB breakdown?

A

Decreased expression of tight junction proteins

142
Q

Only molecules capable of passing through the BBB passively:

A

small lipophilic molecules

143
Q

Pericytes are important for _____ (concerning the BBB)

A

Structural support, expression of tight junction proteins, formation of the basal lamina, and regulating blood flow

144
Q

Homeostatic roles of the BBB

A
  • Maintain ionic homeostasis via ion channels
  • Carrier-mediated transport for nutrients
  • Receptor-mediated transport for larger molecules
  • Protect the brain against toxins
145
Q

The final barrier of the BBB is comprised of:

A

astrocytes

146
Q

The blood-nerve barrier consists of:

A

Endoneurial microvessels, basement membrane, pericytes, and the perineurium

147
Q

Pericyte’s roles in the PNS

A

Help support endothelial cells

148
Q

Schwann cell’s role in the PNS barrier

A

Form a myelin barrier also held together by tight junctions

149
Q

Blood-Nerve Barrier

A

Consists of specialized endothelial cells and is important for maintaining the health and function of peripheral nerves

NEUR*2100 (7 decks)

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