Neurones and Astrocytes Flashcards

1
Q

What is the difference between the CNS and PNS?

A

The difference between the PNS and CNS is about where the cell bodies are.
• Peripheral neurones have their cell bodies outside the brain or spinal chord
• Central neurones have their cell bodies within the brain and spinal chord.

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2
Q

What are the characteristics of neurones?

A

Features of Neurones
• Large nucleus (the biggest neurones probably have the largest nuclei in the body)
• Prominent nucleolus
• Abundant RER
• Well developed Golgi, in keeping with high amounts of protein trafficking via the secretory pathway.
• Abundant mitochondria
• Highly organised cytoskeleton
• Highly organised metabolically active cell.

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3
Q

What are the ways neurones can be classified morphologically?

A

Can be classed based on the number of neurites:
• Unipolar are extremely rare in vertebrates, and are mainly found in insects.
• Multipolar neurones (have multiple dendrites) are the most common in the brain and spinal chord.
• Bipolar neurones are typically sensory neurones.
○ Retinal bipolar cells, sensory cells of the cochlea, and vestibular ganglia are included in this category.
• Pseudo-unipolar neurones (1) have one axon that branches into two - a peripheral and central branch. They are typically sensory neurones that detect pressure and pain. The axon closest to the receptor is the trigger zone for the neurone. The cell body lies within the dorsal root ganglion. The central axon passes into the dorsal (posterior) horn and synapses with another neurone, while the peripheral axon travels through the spinal nerve until it reaches the skin, muscle or joint.

Neurones can also be classed based on their axon length:
• Golgi type I neurones are (multipolar) neurones that connect one part of the brain to another, and so have axons that extend long distances. Examples of these include:
○ Pyramidal cells of the cerebral cortex
○ Purkinje cells of the cerebellum
○ Anterior horn cells of the spinal chord
• Golgi type II neurones are (multipolar) neurones that connect as part of a local circuit, and so have a short axon. Examples include:
○ Stellate cells of the cerebral cortex and cerebellum.

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4
Q

What are the different ways neuronal circuits can be organised?

A
  • Divergence: spreading stimulation to multiple neuronal pools in the CNS
  • Convergence: a mechanism providing input to a single neurone from multiple sources
  • Serial processing: when neurones or pools work together in a sequential manner.
  • Parallel processing: when multiple neurones or pools of neurones process information simultaneously
  • Reverberation: a feedback mechanism that may be excitatory or inhibitory
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5
Q

What is meant by saying neurones are polarised cells?

A

Neurones are polarised cells. This does not refer to the electrical polarity, but to the fact that there are molecularly distinct compartments.

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6
Q

How is the polarity of a neurone determined?

A

Neurones initially extend several short neurites (term used to describe both axons and dendrites). The one that starts growing faster becomes the axon, while the others develop into dendrites. The axonal compartment is kept separate from the somato-dendritic compartment. This is important as certain proteins, complexes and cargos must be directed to particular regions of the neurone. For example, the machinery for neuro-exocytosis must be directed to the synapse, sodium channels to the Nodes of Ranvier, and receptors involved in axon growth and guidance must be directed to the growth cone etc.

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7
Q

Give two examples of somato-dendritic specific components

A

Examples of somato-dendritic specific components include:
• Microtubule stabilising protein MAP2B.
• All the neurotransmitter receptors, postsynaptic density (PSD) scaffolding and signalling proteins required at the post-synaptic area.

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8
Q

Describe the organisation of the neuronal receptive/input field

A

Dendrites are the major area of reception of incoming information. They spread from the cell body and branch frequently, greatly increasing the surface area of the neurone. Primary dendrites are those directly connected to the cell body, while secondary dendrites are those attached to primary dendrites.

They are often covered in protrusions called spines. The formation of these spines depends on external signalling.

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9
Q

What is the most plastic part of the CNS?

A

Dendritic spines

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10
Q

What are the different morphologies dendritic spines can assume?

A
  • Stubby
  • Thin
  • Mushroom
  • Filopodium
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11
Q

Give three examples of axon specific components

A

Axon-specific components include:
• Neurofilaments are only present in the axon where they are important for strength.
• Microtubule stabilising protein tau
• Cell adhesion molecules L1 (NgCAM), TAG-1.

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12
Q

Describe the features of an axon

A

Axons conduct impulses away from the cell body, emerging away from the axon hillock. There is usually only one per cell, but may branch after leaving cell body into axon collaterals.

They have prominent microtubules and neurofilaments. They can be myelinated or unmeylinated. Has a large number of mitochondria to maintain membrane potential.

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13
Q

What are the domains of a Node of Ranvier?

A

In order to maintain action potential condiction at high speed, the axonal membrane is organised into specific domains: juxtaparanode, paranode and node (of Ranvier)

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14
Q

What proteins are important in maintaining the Node of Ranviers

A

There is an array of proteins important for maintaining this system:
• Na+ channels are achored to actin filaments by various proteins such as Ankorin B.
• Cell adhesion molecules bind loops of oligodendrocytes to the axon - to form a tight structure - this is to 1) stop leakage of current and 2) stop proteins moving from node of Ranvier to myelinated axon.
○ Animal models without this tight adhesion can lead to severe neurological disorders
○ These adhesions can be lifted in MS
• K+ channels in the paranode?

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15
Q

What are the two types of synapses?

A

Axons often branch extensively close to their target, forming a terminal arbour. They form synaptic terminals with target. These synapses can either be boutons or varicosities.

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16
Q

How do synaptic vesicles reach the axon terminal?

A

Synaptic vesicles, packed in the Golgi are shipped by fast anterograde transport.

17
Q

How is synapse organisation related to function? i.e which synapses tend to be inhibitory etc?

A

Neurones receive multiple synaptic inputs.
• Most synapses are axo-dendritic, which are usually excitatory
• Axo-somatic are usually inhibitory
• Axo-axonic are usually modulatory. These would have to happen in the Nodes of Ranvier.

Competing inputs are integrated in the post-synaptic neurone, to decide whether an axon potential should be initiated at the axon hillock.

18
Q

What are the major categories of neurotransmitters?

A
  • Amino acids
  • Amines
  • Neuropeptides
19
Q

What amino acids act as neurotransmitters?

A

Gamma-aminobutyric acid (GABA)
Glutamate (Glu)
Glycine (Gly)

20
Q

What amines act as neurotransmitters?

A
Acetylcholine (ACh) 
Dopamine (DA) 
Epinephrine 
Histamine 
Norepinephrine (NE) 
Serotonin (5-HT)
21
Q

What neuropeptides act as neurotransmitters?

A
Cholecystokinin (CCK)
Dynorphin
Enkephalins (Enk)
N-acetylaspartylglutamate (NAAG) 
Neuropeptide Y 
Somatostatin
Substance P
Thyrotropin-releasing hormone 
Vasoactive intestinal polypeptide (VIP)
22
Q

What percentage of the brain are glial cells?

A

40%

23
Q

What are the main properties of astrocytes?

A
  • Are called astrocytes because they have many thin processes which extend around capillaries, synapses and surface of neurones.
  • Their cytoskeleton consists of GFAP (Glial, Fibrillary Acid Protein - an intermediate filament protein found in astrocytes and radial glia), microtubules and actin.
  • Have glycogen granules which act as a store of energy
  • They have a large nucleus and cytoplasm
  • Rough ER, Golgi apparatus.
24
Q

What components of the brain do astrocytes connect to?

A
Astrocytes connect to many different cells. Such as:
• Capillary endothelial cells
• Neuronal cell bodies
• Initial segment
• Axons (at nodes)
• Dendrites
• Synapses
• Ependymal cells lining the ventricles
• Pial surface of the brain
25
Q

What are the subtypes of astrocytes and where are they found?

A

There are subtypes of astrocytes, the two main ones are fibrous astrocytes (long processes) and protoplasmic astrocytes (much shorter processes, but greater in number).
• We typically find the protoplasmic astrocytes in the grey matter
• We typically find the fibrous astrocytes in the white matter.

Bergmann glial cells are found in the cerebellum. They have more of a structural function. The astrocytes in the subventricular zone act as stem cells, as a precursor for neurones.

26
Q

What are the functions of astrocytes?

A
  • Modulation of synaptic function
  • Metabolic functions
  • Maintenance of the BBB
  • Regulation of blood flow
  • Release neuroprotective factors
  • Recycling of neurotransmitters
  • Produce anti-inflammatory cytokines
  • Removal of waste products
  • Potassium reservoir
  • Structural support
  • Stem cells
27
Q

How do astrocytes aid in modulation of synaptic function?

A

Synaptogenesis and synaptic pruning. In synaptic pruning the astrocyte (and microglia) phagocytose part of the synapse during development. Astrocytes express several membrane proteins and enzymes that are critical for uptake of glutamate at the synapses.

28
Q

How do astrocytes aid in metabolic needs of neurones?

A

○ Production of cholesterol
○ Provide energy to the brain in form of lactate produced from glycogen. Astrocytes are the only cells in the brain that store glycogen. It has enough to last tens of minutes.
○ They also synthesis Apolipoprotein E (involved in clearance of proteins such as amyloid).

29
Q

How do astrocytes aid in the maintenance of the BBB?

A

○ They act as the gateway between the general circulation an the neurones in the CNS. Astrocyte end-feet wrap around endothelial cells, providing a gateway for nutrients into the CNS, and removal of metabolites from the CNS.
○ They express a large array of transport proteins for nutrients (e.g. glucose) and metabolites.
○ The BBB is formed by very tight associations of brain capillary endothelial cells. It is essential for controlling entry of molecules and ions into the CNS.

30
Q

How do astrocytes regulate blood flow to the brain?

A

By causing vasoconstriction and vasodilation of blood vessels via the arachidonic acid and prostaglandin pathways respectively.

○ Astrocytes have an intimate relationship with blood vessels in the brain as their endfoot processes completely envelop all cerebral blood vessels.

○ Neurotransmitters released from active neurons evoke Ca2+ increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid from astrocyte endfeet onto blood vessels. Synthesis of prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs) dilate blood vessels, whereas 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels.

31
Q

How are astrocytes neuroprotective?

A

release of growth factors such as Glial-cell Derived Neurotrophic Factor - GDNF, FGF and IGF.

32
Q

Give an example of how astrocyte help in the removal of waste products

A

Removal of waste products. AQP4 (Aquaporin 4) is a protein that exists in the areas of the astrocytes that surround the blood brain barrier. AQP4 is important in the removal of waste products from the brain during sleep.

33
Q

Why is it important astrocytes act as potassium buffers?

A

maintaining a good supply of potassium, but keeping away from the extracellular space until required. They also remove potassium ions from the extracellular space, which is essential for neuronal function, as after intense neuron firing, local concentrations of potassium can be quite high. Potassium is redistributed from these regions, to other regions where potassium is needed. This is called spatial buffering.

34
Q

How do astrocytes aid in structural support?

A

Radial glia span the cortex radially from the inner to outer layers. They are important for neuronal migration. Examples are the Bergmann glia in the cerebellum and the Muller cells in the retina.

35
Q

How can astrocytes act as stem cells?

A

Radial glia can give rise to neurones, astrocytes and ependymal cells - seem multipotential. Even mature astrocytes seem to have the ability to transform into neurones.

○ In an experiment, they took glial progenitors from humans and transplanted them into mice. These converted into neurones, and made the mice smarter!

36
Q

How are astrocytes implicated in neurodegeneration?

A

In neurodegenerative diseases, astrocytes can become active, and can proliferate and form scars around plaques (gliosis). They also:
• Increase glutamate cytotoxicity
• Increase levels of caclium and ATP release
• Increase production of nitric oxide
• Accumulation of superoxide dismutase
• Formation of glial scars (unsure if this is actually a bad thing, as it is trying to surround and protect neurone?)

37
Q

What is the role of astrocytes in injury?

A

Astrocytes also have a role in injury. They respond to a range of CNS insults including, TBI, SCI, stroke, brain tumours, inflammatory disorders and a range of neurodegenerative diseases (Liddelow et al 2017). They:

  • aid in phagocytosis of synapses
  • changes in secretion of neurotrophins
  • clearance of debris and dead cells
  • repair the blood-brain-barrier
  • form scars to enclose the necrotic lesion (Liddelow et al 2017).

Removal of the glial scars lead to worsened injury outcome, and axon dieback after spinal cord injury. (Anderson et al 2016).

Astrocytes have an important role in the maintenance and repair of the blood-brain-barrier. The astrocytic end-feet act as a gateway for nutrients into the CNS, and removal of metabolites from the CNS. They express a large array of transport proteins for nutrients (e.g. glucose) and metabolites. The BBB is formed by very tight associations of brain capillary endothelial cells. It is essential for controlling entry of molecules and ions into the CNS. The BBB protects the brain from cytokines and ROS which can cause damage and neurodegeneration.

38
Q

How do reactive astrocytes contribute to disease pathology?

A

Interestingly, there is a shift to the focus on astrocytes; it may be instead that microglia activate astrocytes to become neurotoxic. Some have labelled astrocytes A1 and A2, where A1 is inflammatory, and A2 exhibits a neuroprotective phenotype.

Reactive astrocytes are known to:

  • inhibit axon regeneration
  • upregulate genes responsible for induction of synapse formation, which can lead to unwanted synapses causing epilepsy or neuropathic pain.
  • A1 astrocytes are also known to release neurotoxic factors, toxic to some neurones.

A1 reactive astrocytes are present in the brain regions involved in neurodegeneration in a variety of diseases including MS, Alzheimer’s disease, ALS, Parksinson’s disease and Huntington’s Disease. The NFkB pathway may be implicated here. The NFkB pathway controls cytokine production and cell survival and is strongly associated with neuroinflammation, as well as neuroinflammatory reactivity in astrocytes and microglia. Studies of NFkB activation of astrocytes show that this may be important in animal models of Alzheimer’s disease and Huntington’s Disease.