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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
Q

Describe the morphology of neurons

A

Cell body
Dendrites
Axon
• axon terminals

Can be:
• Bipolar
• Unipolar
• Multipolar

26
Q

Describe the arrangement of neurons within the brain

A

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
Q

Describe the general features of glial cells

A

Everything that is neither neuron nor blood vessel

Include:
 • Oligodendrocytes (produce myelin)
 • Astrocytes (homeostasis)
 • Microglia (immune surveillance)
 • Ependymal cells
28
Q

What are oligodendrocytes?

Describe their structure and function

A
  1. Function
    • Myelin production
    • Structural neuronal support
  2. Structure:
    In steady state:
    • Numerous processes
    • Small amount of cytoplasm
29
Q

How many axons does a single oligodendrocyte myelinate?

A

A single oligodendrocyte myelinates 4-40 axons

Wraps around axons in segments

30
Q

What are the unmyelinated gaps on the axon?

A

Nodes of Ranvier

31
Q

What is the function of myelin?

A

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
Q

What is the internodal axonal membrane?

A

The part of the axon that is myelinated

33
Q

What are astrocytes?

Describe their function and structure

A

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
Q

Describe the organisation of astrocytes

A

Highly organised organisation into non-overlapping domains

35
Q

What are Endfeet?

Describe the function

A

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
Q

What are the emerging roles of astrocytes?

A
  • Modulation of synaptic activity
  • Neurogenesis
  • Post-injury repair
  • Memory formation
37
Q

What are microglia?

A

Resident macrophages in the brain

Arise from mononuclear phagocyte precursor, not the brain itself.

38
Q

When do microglia enter the brain?

A

During development, before formation of the BBB

39
Q

Where are microglia located?

A

Equally distributed throughout grey and white matter

40
Q

What is the function of microglia?

A
  • Homeostasis
  • First line of defence against viruses, bacteria, parasites
  • Remove debris
41
Q

What are the phenotypes of microglia?

A

Four different phenotypes depending on degree of activation:
1. Ameboid
• During development and perinatal period

  1. Ramified
    • in mature CNS
    • under normal conditions
  2. Reactive
    • arise in response to sublethal injury
    • haven’t yet taken on the phagocytic role
  3. Phagocytic

Ramified → Reactive → Phagocytic

42
Q

Describe the immune privilege in the brain

A
  • 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
Q

Describe Peter Medawar’s demonstration of immune privilege in the brain

What was the significance of this?

A
  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

  1. Graft into periphery, then graft into brain → rejection

This must indicate that lymphocytes can enter the brain under certain circumstances

44
Q

What is the neuropil?

A

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
Q

Describe leukocyte penetration into the CNS

A

Specialised:

Homeostatic conditions:
• Low levels of trafficking
• Cells rarely enter the neuropil

Inflammation and disease:
• Increased leukocyte infiltration

46
Q 
What is the tissue origin of the following?
 • Microglia
 • Neurons
 • Astrocytes
 • Oligodendrocytes
 • Ependyma
A

Microglia: Mesoderm

Everything else: Neuroectoderm

47
Q

What are the stem cells in the brain?

Where are they located?

A

Neural progenitor cells
(a type of adult stem cell)

Location:
• Neurogenic niches (discrete locations)

48
Q

What is the differentiation capacity of neural progenitor cells?

A

Can be induced to differentiate into:
• Neurons
• Astrocytes
• Oligodendrocytes

NB can not microglia, because these have a different cell origin (mesoderm)

49
Q

What does the BBB separate?

A

Separates the blood and the Brain/CSF

50
Q

Is there transport between the brain and the CSF?

A

Yes, to a certain degree

51
Q

Where are the DCs in the brain?

A

No DCs in the brain

52
Q

What is the function of neurons?

A

Communication between cells

This is carried out by transmission of electrical impulses

53
Q

What is Nissl substance?

A

ER in neurons

54
Q

What are neurofibrils?

A

Cytoskeleton in the axon

Function:
• Structure
• Vesicular transport along axon

PATH30001 - Mechanisms of Disease (34 decks)

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