Lecture 23 - CNS 1 Flashcards
What is the PNS?
What cell types make it up?
Peripheral nervous system
• outside the brain and spinal cord
Consists of: • Afferent: - Sensory neurons • Efferent: - Somatic: motor neurons - Autonomic: sympathetic & parasympathetic
How much does the brain weigh?
1.5 kg
How much of the cardiac output does the brain receive?
20%
i.e. high metabolic demand
What are the nutrient requirements of the brain?
O2 for energy production
Glucose for fuel
Describe what happens when blood flow to the brain stops
Indicate a time frame
Why is this?
Seconds: brain function stops
Minutes: neurons die
This is because the brain has no energy reserves
What is the regenerative capacity of the CNS?
Very limited: neurons are terminally differentiated, permanent cells that cannot re-enter the cell cycle
What protects the brain?
Skull Meninges BBB CSF Glia cells
How long is the spinal cord?
45 cm
What protects the spinal cord?
The vertebral column
Meninges
What connects the brain and the spinal cord?
The brain stem
List the major areas in the brain
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
Describe briefly the link between CNS area affected and clinical symptoms in Multiple sclerosis
Lesions anywhere in CNS
→ Range of clinical manifestations
What are the meninges?
Tissue layers around the CNS for protection:
• Pia mater
• Arachnoid mater
• Dura mater
Describe briefly the link between CNS area affected and clinical symptoms in Alzheimer’s disease
Amyloid plaques in cerebral cortex and hippocampus
→ Memory and cognition loss
Describe briefly the link between CNS area affected and clinical symptoms in Parkinson’s disease
Loss of SN dopaminergic cells
→ Motor deficit
Lewy bodies throughout brain
→ Cognitive deficits
Describe briefly the link between CNS area affected and clinical symptoms in Prion disease
Loss of thalamic nuclei
→ hormone irregularities
→ disruption of sleep / wake cycles
What produces CSF?
Choroid plexus in the ventricles
Describe the location of CSF, and how it is recycled
Subarachnoid space
Reabsorbed back into the blood through arachnoid granulations into venous circulation
What is the function of CSF?
Shock-absorption: prevents brain bumping against skull
What is the BBB?
Describe the structure and function
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
Describe the location and function of pericytes
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
What can and can’t move across the BBB?
Movement across: • Small, lipid soluble solutes Solutes with a transporter or channel protein: • Glucose • Amino acids • Ions
No movement:
• Plasma components
• RBCs
• Leukocytes
What are the two different tissue types in the brain?
What is the basis of this?
Grey matter
• Outer part
• Cell bodies and dendrites
White matter:
• Myelinated axons
• Inner part
What are the different types of neurons?
Give a brief description of their respective functions
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
Describe the morphology of neurons
Cell body
Dendrites
Axon
• axon terminals
Can be:
• Bipolar
• Unipolar
• Multipolar
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
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
What are oligodendrocytes?
Describe their structure and function
- Function
• Myelin production
• Structural neuronal support - Structure:
In steady state:
• Numerous processes
• Small amount of cytoplasm
How many axons does a single oligodendrocyte myelinate?
A single oligodendrocyte myelinates 4-40 axons
Wraps around axons in segments
What are the unmyelinated gaps on the axon?
Nodes of Ranvier
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
What is the internodal axonal membrane?
The part of the axon that is myelinated
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:
- Protoplasmic
• in grey matter
• radial spreading of processes - Fibrous
• in white matter
• arranged in rows between axon bundles
Describe the organisation of astrocytes
Highly organised organisation into non-overlapping domains
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
What are the emerging roles of astrocytes?
- Modulation of synaptic activity
- Neurogenesis
- Post-injury repair
- Memory formation
What are microglia?
Resident macrophages in the brain
Arise from mononuclear phagocyte precursor, not the brain itself.
When do microglia enter the brain?
During development, before formation of the BBB
Where are microglia located?
Equally distributed throughout grey and white matter
What is the function of microglia?
- Homeostasis
- First line of defence against viruses, bacteria, parasites
- Remove debris
What are the phenotypes of microglia?
Four different phenotypes depending on degree of activation:
1. Ameboid
• During development and perinatal period
- Ramified
• in mature CNS
• under normal conditions - Reactive
• arise in response to sublethal injury
• haven’t yet taken on the phagocytic role - Phagocytic
Ramified → Reactive → Phagocytic
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
Describe Peter Medawar’s demonstration of immune privilege in the brain
What was the significance of this?
- Skin graft into brain → no rejection
- 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
- Graft into periphery, then graft into brain → rejection
This must indicate that lymphocytes can enter the brain under certain circumstances
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
Describe leukocyte penetration into the CNS
Specialised:
Homeostatic conditions:
• Low levels of trafficking
• Cells rarely enter the neuropil
Inflammation and disease:
• Increased leukocyte infiltration
What is the tissue origin of the following? • Microglia • Neurons • Astrocytes • Oligodendrocytes • Ependyma
Microglia: Mesoderm
Everything else: Neuroectoderm
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)
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)
What does the BBB separate?
Separates the blood and the Brain/CSF
Is there transport between the brain and the CSF?
Yes, to a certain degree
Where are the DCs in the brain?
No DCs in the brain
What is the function of neurons?
Communication between cells
This is carried out by transmission of electrical impulses
What is Nissl substance?
ER in neurons
What are neurofibrils?
Cytoskeleton in the axon
Function:
• Structure
• Vesicular transport along axon
