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PATH30001 - Mechanisms of Disease > Lecture 23 - CNS 1 > Flashcards

Lecture 23 - CNS 1 Flashcards

1
Q

What is the PNS?

What cell types make it up?

A

Peripheral nervous system
• outside the brain and spinal cord

Consists of:
 • Afferent: 
- Sensory neurons
 • Efferent: 
- Somatic: motor neurons
- Autonomic: sympathetic & parasympathetic
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2
Q

How much does the brain weigh?

A

1.5 kg

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3
Q

How much of the cardiac output does the brain receive?

A

20%

i.e. high metabolic demand

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4
Q

What are the nutrient requirements of the brain?

A

O2 for energy production

Glucose for fuel

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5
Q

Describe what happens when blood flow to the brain stops
Indicate a time frame

Why is this?

A

Seconds: brain function stops
Minutes: neurons die

This is because the brain has no energy reserves

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6
Q

What is the regenerative capacity of the CNS?

A

Very limited: neurons are terminally differentiated, permanent cells that cannot re-enter the cell cycle

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7
Q

What protects the brain?

A 
Skull
Meninges
BBB
CSF
Glia cells
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8
Q

How long is the spinal cord?

A

45 cm

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9
Q

What protects the spinal cord?

A

The vertebral column

Meninges

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10
Q

What connects the brain and the spinal cord?

A

The brain stem

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11
Q

List the major areas in the brain

A

Frontal lobe:
• Prefrontal cortex
• Motor cortex
• Somatosensory cortex

Temporal lobe
• Auditory receiving area

Parietal lobe

Occipital lobe

Thalamus

Brain stem:
• Midbrain
• Pons
• Medulla

Ventricles:
• Lateral
• 3rd & 4th

• Cerebellum

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12
Q

Describe briefly the link between CNS area affected and clinical symptoms in Multiple sclerosis

A

Lesions anywhere in CNS

→ Range of clinical manifestations

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13
Q

What are the meninges?

A

Tissue layers around the CNS for protection:
• Pia mater
• Arachnoid mater
• Dura mater

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14
Q

Describe briefly the link between CNS area affected and clinical symptoms in Alzheimer’s disease

A

Amyloid plaques in cerebral cortex and hippocampus

→ Memory and cognition loss

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15
Q

Describe briefly the link between CNS area affected and clinical symptoms in Parkinson’s disease

A

Loss of SN dopaminergic cells
→ Motor deficit

Lewy bodies throughout brain
→ Cognitive deficits

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16
Q

Describe briefly the link between CNS area affected and clinical symptoms in Prion disease

A

Loss of thalamic nuclei
→ hormone irregularities
→ disruption of sleep / wake cycles

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17
Q

What produces CSF?

A

Choroid plexus in the ventricles

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18
Q

Describe the location of CSF, and how it is recycled

A

Subarachnoid space

Reabsorbed back into the blood through arachnoid granulations into venous circulation

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19
Q

What is the function of CSF?

A

Shock-absorption: prevents brain bumping against skull

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20
Q

What is the BBB?

Describe the structure and function

A

Blood brain barrier

Structure:
 • Specialised endothelium
 • Tight junctions
 • Basement membrane
 • Pericytes
 • Glial cells
Very difficult to get through

Function:
• Maintenance of chemical composition of the interstitial fluid
• Protection from foreign substances e.g. pathogens
• Protection from physiological substances e.g. cytokines during infection
• Protection from drastic environmental fluctuations e.g. dehydration

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21
Q

Describe the location and function of pericytes

A

Location:
• Adjacent to endothelial cells (share a common basement membrane)

Function:
• Contribute to stability (mechanical and biochemical)
• Release growth factors
• Regulate blood flow through contraction

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22
Q

What can and can’t move across the BBB?

A 
Movement across:
 • Small, lipid soluble solutes
 Solutes with a transporter or channel protein:
 • Glucose
 • Amino acids
 • Ions

No movement:
• Plasma components
• RBCs
• Leukocytes

23
Q

What are the two different tissue types in the brain?

What is the basis of this?

A

Grey matter
• Outer part
• Cell bodies and dendrites

White matter:
• Myelinated axons
• Inner part

24
Q

What are the different types of neurons?

Give a brief description of their respective functions

A

Sensory
• Afferent: periphery → CNS
• Detection and experience of environment

Autonomic
• Innervation of organs
• Efferent: CNS → periphery

Motor
• Skeletal muscle innervation
• Efferent: CNS → periphery

Interneurons
• Within CNS

25
Describe the morphology of neurons
Cell body Dendrites Axon • axon terminals Can be: • Bipolar • Unipolar • Multipolar
26
Describe the arrangement of neurons within the brain
Neuronal function is dependent on connections to other neurons • Tracts in the spinal cord * Ganglia: collection of neurons in PNS * Nuclei: collections of neurons in CNS • Cerebral cortex: 6 layers
27
Describe the general features of glial cells
Everything that is neither neuron nor blood vessel ``` Include: • Oligodendrocytes (produce myelin) • Astrocytes (homeostasis) • Microglia (immune surveillance) • Ependymal cells ```
28
What are oligodendrocytes? | Describe their structure and function
1. Function • Myelin production • Structural neuronal support 2. Structure: In steady state: • Numerous processes • Small amount of cytoplasm
29
How many axons does a single oligodendrocyte myelinate?
A single oligodendrocyte myelinates 4-40 axons | Wraps around axons in segments
30
What are the unmyelinated gaps on the axon?
Nodes of Ranvier
31
What is the function of myelin?
Enables saltatory conduction through insulation of axon * Decrease current leakage across internodal axon membrane * Increased velocity of conduction • Decrease space taken up, because neurons do not need to be so large Very metabolically active
32
What is the internodal axonal membrane?
The part of the axon that is myelinated
33
What are astrocytes? | Describe their function and structure
Glial cells ``` Function: • Support and maintain the CNS • Involved in almost every CNS function: - Development - Maintenance of synapse microenvironment - Synthesis of neurotransmitters - Supply of energy to neurons - pH regulation ``` Structure: two morphological types: 1. Protoplasmic • in grey matter • radial spreading of processes 2. Fibrous • in white matter • arranged in rows between axon bundles
34
Describe the organisation of astrocytes
Highly organised organisation into non-overlapping domains
35
What are Endfeet? | Describe the function
These are the ends of the astrocytes processes Function: • Contact blood vessels • Interaction with ependymal cells (which produce CSF) • Interaction with nodes of Ranvier
36
What are the emerging roles of astrocytes?
* Modulation of synaptic activity * Neurogenesis * Post-injury repair * Memory formation
37
What are microglia?
Resident macrophages in the brain | Arise from mononuclear phagocyte precursor, not the brain itself.
38
When do microglia enter the brain?
During development, before formation of the BBB
39
Where are microglia located?
Equally distributed throughout grey and white matter
40
What is the function of microglia?
* Homeostasis * First line of defence against viruses, bacteria, parasites * Remove debris
41
What are the phenotypes of microglia?
Four different phenotypes depending on degree of activation: 1. Ameboid • During development and perinatal period 2. Ramified • in mature CNS • under normal conditions 3. Reactive • arise in response to sublethal injury • haven't yet taken on the phagocytic role 4. Phagocytic Ramified → Reactive → Phagocytic
42
Describe the immune privilege in the brain
* Limited ability for the immune system to penetrate the BBB * No lymphatic draining: no representation of the antigen in the brain in the lymphoid organs * No DCs to detect antigen * Low levels of MHC expression * Microglial cells and astrocytes can not sustain immune responses
43
Describe Peter Medawar's demonstration of immune privilege in the brain What was the significance of this?
1. Skin graft into brain → no rejection 2. Skin graft into periphery → rejection However: If the response is first primed in the periphery (graft into the periphery), there will be a specific immune response when the graft is put into the brain 3. Graft into periphery, then graft into brain → rejection This must indicate that lymphocytes can enter the brain under certain circumstances
44
What is the neuropil?
Any area in the nervous system composed of mostly unmyelinated axons, dendrites and glial cell processes A synaptically dense region containing a relatively low number of cell bodies
45
Describe leukocyte penetration into the CNS
Specialised: Homeostatic conditions: • Low levels of trafficking • Cells rarely enter the neuropil Inflammation and disease: • Increased leukocyte infiltration
46
``` What is the tissue origin of the following? • Microglia • Neurons • Astrocytes • Oligodendrocytes • Ependyma ```
Microglia: Mesoderm Everything else: Neuroectoderm
47
What are the stem cells in the brain? | Where are they located?
Neural progenitor cells (a type of adult stem cell) Location: • Neurogenic niches (discrete locations)
48
What is the differentiation capacity of neural progenitor cells?
Can be induced to differentiate into: • Neurons • Astrocytes • Oligodendrocytes NB can not microglia, because these have a different cell origin (mesoderm)
49
What does the BBB separate?
Separates the blood and the Brain/CSF
50
Is there transport between the brain and the CSF?
Yes, to a certain degree
51
Where are the DCs in the brain?
No DCs in the brain
52
What is the function of neurons?
Communication between cells This is carried out by transmission of electrical impulses
53
What is Nissl substance?
ER in neurons
54
What are neurofibrils?
Cytoskeleton in the axon Function: • Structure • Vesicular transport along axon

PATH30001 - Mechanisms of Disease (34 decks)

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