Neurons and Glia 4 Flashcards
(105 cards)
1
Q
Give two ways that neurones may get injured in the CNS. (2)
A
- Disease processes (AD, PD, MND, HD)
- Interruption of axons (axotomy)
1
Q
Why do injured neurones in the PNS tend to regenerate, while in the CNS they don’t? (2)
A
- In the PNS, injured nerves tend to regenerate due to Schwann cell activation
- In the CNS active processes prevent axon regeneration
2
Q
What are the clinical consequences of a lesion in the cervical spinal cord?
How are motor and sensory neurones affected differently? (3)
A
Tetraplegia/quadriplegia
- Large part of motor neurone will die
- Small part of sensory neurone will die
3
Q
What are the clinical consequences of a lesion in the caudal portion of the spinal cord?
How are motor and sensory neurones affected differently? (3)
A
Paraplegia
- Small part of motor neurone will die
- Large part of sensory neurone will die
4
Q
True or false? (1)
If an axon is severed, the whole neurone will die and will no longer be functional.
A
False - if an axon is severed the area below the region (away from the soma) will degenerate, but the rest will stay in tact.
5
Q
What is the advantage in a spinal cord lesion of having only a small section of axon degenerate? (1)
A
The smaller the section of axon which dies means it is more likely to grow back and regenerate.
6
Q
Give 10 complications of spinal cord lesions. (10)
A
- Bladder
- Bowel
- Impaired skin sensation
- Circulatory control
- Respiratory system
- Muscle tone (spasticity/flaccidity)
- Obesity
- Sexual health
- Pain
- Decreased life span
7
Q
Why do spinal cord lesions sometimes result in a decreased life span? (1)
A
With cervical lesions, autonomic control of organs such as heart is reduced, meaning a decreased lifespan.
8
Q
Briefly give two reasons why the body has developed an active process to prevent CNS regeneration. (2)
A
- Traditionally, CNS injuries occurred near end of life
- Prevent aberrant sprouting and limit structural changes in brain
9
Q
Give two ways that the CNS has evolved to prevent aberrant axon sprouting and preserve the complex neural networks formed during development in normal function. (2)
A
- Astrocytes release CSPG
- Oligodendrocytes ensheath axons and produce myelin-based inhibitory factors
10
Q
Give four ways in which spinal cord injuries are currently treated, and the general benefit/aim of each treatment. (4)
A
- Methylprednisolone (reduce inflammation)
- Traction and immobility (prevent further injury)
- Surgery to remove bone/bullet fragments (prevent further injury)
- Experimental therapies
11
Q
Give three processes/changes that occur at the site of a spinal cord lesion. (3)
A
- Release of myelin-based inhibitory signals
- Production of glial scar
- Appearance of dystrophic growth cones on transected axons
12
Q
Give two ‘structures’ which release myelin-based inhibitory factors at the site of a spinal cord lesion. (2)
A
- Myelin debris
- Damaged oligodendrocytes
13
Q
How do myelin-based inhibitory factors contribute to the inability of the CNS to regenerate at the site of a spinal cord lesion? (1)
A
Cause undamaged axons to die
14
Q
Give four examples of myelin-based inhibitory factors. (4)
A
- MAG (myelin associated glycoprotein)
- NoGo
- Ephrin B3
- Oligodendrocyte myelin glycoprotein (OMgp)
15
Q
Name the process by which astrocytes form a glial scar at the site of CNS injury. (1)
A
Reactive gliosis
16
Q
Describe the advantages and disadvantages of reactive astrocytes producing increased GFAP intermediary filaments at the site of CNS injury. (3)
A
- Forms a scar to repair BBB
- This prevents an overwhelming inflammatory response
- However prevents axon regeneration
17
Q
What triggers glial scar formation at the site of CNS injury? (1)
A
Introduction of non-CNS molecules due to disrupted BBB
18
Q
True or false? (1)
Dystrophic end bulbs which form on the ends of transected axons are dead structures which do not perform any functions.
A
False - they display protein turnover and other processes, however remain dormant without losing the ability to regenerate
19
Q
Reactive astrocytes which form the glial scar at the site of CNS injury produce increased levels of which two substances? (2)
A
- Intermediary GFAP filaments
- CSPGs
20
Q
What does CSPG stand for in the context of CNS regeneration? (1)
A
Chondroitin sulphate proteoglycan
21
Q
Describe the secretion rate and concentrations of CSPG in a spinal cord lesion. (2)
A
Secreted in first 24hrs
Concentration highest in the centre of a lesion
22
Q
Which cells have been found to project further into a CNS lesion producing CSPGs, and which cells have been found to not project very far into lesions secreting CSPGs? (3)
A
Project far = retinal ganglion cells
Do not project far = DRG and forebrain neurones
23
Q
Give three general strategies which could be investigated as methods to allow CNS regeneration. (2)
A
- Add stimulating factors
- Remove inhibitory factors
- Use glial cells to construct a growth pathway
24
Give two possible ways that glial cells may be used to construct pathways for CNS regeneration. (2)
- Transplanted embryonic cells
- Transplanted peripheral nerve (and Schwann) cells
25
Suggest three ways that exploiting the intrinsic ability of nerve cells to regrow or inhibiting methods to prevent CNS regeneration could potentially be used for spinal cord lesion treatment. (3)
- Digest CSPG after an injury with chondroitinase
- Block effects of myelin-based inhibitory signals (specifically NoGo-A) with targeted antibodies
- Enhance intrinsic growth factors such as NGF
26
Describe how CNS regeneration may be experimentally stimulated in animals using peripheral nerve graft and chondroitinase. (2)
- PNG forms a bridge to connect sides of lesion
- Chondroitinase injected on either side of bridge to encourage CNS to grow into bridge
27
In a study where a PNG and chondroitinase were used to stimulate CNS regeneration of the phrenic nerve supplying the diaphragm, respiratory function was restored, but at a lower resp rate.
What adaptation would the animals have to make after this experiment in terms of breathing function? (1)
They would have to breathe more deeply than before.
28
What may happen if spinal cord derived human neural precursor cells are grafted into the site of a spinal cord injury in a rhesus monkey? (2)
- Monkey axons regenerate into graft
- Human axons extend from grafts into monkey spinal cord
29
There is a type of naturally-occurring cell in the CNS of the human body which may be able to facilitate axon regrowth.
Name this cell. (1)
Olfactory ensheathing cell
30
Describe the normal physiological role of olfactory ensheathing cells. (3)
Glial cells
which wrap around regenerating olfactory neurones
and which may allow these neurones to travel from the olfactory epithelium in the PNS to the olfactory bulb in the CNS.
31
How may olfactory ensheathing cells be used in research looking into CNS regeneration? (2)
OECs can be cultured and transplanted into sites of CNS injury
they may support axon regrowth.
32
Describe how CNS regeneration may be experimentally stimulated in humans using peripheral nerve graft and olfactory ensheathing cells. (3)
Patient's own OECs harvested
PNG inserted as bridge across severed spinal cord
OECs injected at junction between PNG and spinal cord
33
True or false? (1)
Current research investigating CNS regeneration using peripheral nerve grafts has only so far been successful in regenerating afferent nerve fibres.
False - it has been shown to be able to regenerate both efferent and afferent nerve fibres
34
Seizures most often manifest in which three areas of the brain? (3)
- Cortex
- Hippocampus
- Thalamus
35
What is epilepsy? (1)
The clinical manifestation of excessive or hypersynchronous neuronal activity, usually self-limited.
36
Give two large categories of seizure. (2)
- Partial
- Generalised
37
Give three types of partial seizure. (3)
- Simple partial
- Complex partial
- Partial evolving to secondary generalised
38
Describe a simple partial seizure. (1)
Focal symptoms with awareness
39
Describe a complex partial seizure. (1)
Focal symptoms with impaired awareness
40
What is meant by a generalised seizure? (1)
Widespread activity which affects consciousness and awareness.
41
Give four types of generalised seizure. (4)
- Absence
- Myoclonic
- Clonic
- Tonic
42
Which type of seizure can be described as 'non convulsive'? (1)
Absence
43
Describe a myoclonic seizure. (1)
Brief shock-like jerks
44
Describe a clonic seizure. (1)
Repeated muscle contraction/jerking and relaxation
45
Describe a tonic seizure. (1)
Muscles become stiff and tense
46
Give five stimuli which may cause seizures. (5)
- Fever
- Hypoglycaemia
- Alcohol withdrawal
- Head injury
- Drugs (pentylenetetrazol/pilocarpine/kainate)
47
Give five causes of epilepsy. (5)
- Idiopathic
- Trauma
- Infection
- Brain tumours
- Genetic abnormalities (channelopathies)
48
What is the difference between seizures and epilepsy? (1)
Seizures can be induced in anyone by appropriate stimuli, while epilepsy is characterised by repeated unprovoked seizures.
49
Give three potential treatments for epilepsy. (3)
- Drugs
- Surgery
- Ketogenic diet
50
Describe a hypothesis suggesting how a ketogenic diet may help treat epilepsy. (3)
Lack of carbohydrate may limit glycolysis
so energy cannot be obtained to restore Vm
and continuous action potentials cannot be produced.
51
Give two medical tests (along with history and neurological exam) that are often used when diagnosing epilepsy. (2)
- MRI to rule out tumours
- EEG
52
Describe the activity of a single neurone during a seizure. (2)
Initial sustained depolarisation
followed by rhythmic bursts of activity (self-limiting).
53
List five roles of astrocytes may be defective in epilepsy, causing increased neuronal excitability. (5)
- Potassium buffering
- Gap junctions
- Aquaporin channels
- Glutamate transport
- GABA transporters
54
Why is it difficult to determine how astrocytes may be involved in epilepsy? (1)
It is difficult to know which pathologies cause epilepsy, and which are caused BY epilepsy.
55
How may potassium buffering be defective in astrocytes in people who have epilepsy? How may this cause epilepsy? (2)
Astrocytes may have reduced or less effective Kir4.1 channels
leading to increased extracellular potassium.
56
Describe how aquaporins in astrocytes may play a role in epilepsy. (3)
- Potassium buffering by Kir4.1 channels is dependent on aquaporins (AQP4)
- to take up water and balance the osmotic effects of increased intracellular potassium
- Dislocation of AQP4 may impair astrocytic potassium buffering
57
Name the molecule which makes up gap junctions in astrocytes. (1)
Connexin 43
58
Describe how impaired gap junctions in astrocytes may lead to epileptic activity. (2)
- Gap junctions required to transport energy from blood vessels to synapses
- Impaired gap junctions lead to reduced energy for potassium and glutamate buffering
59
Why might evidence suggest that impaired gap junctions in astrocytes have contradictory effects, potentially causing both proepileptic and antiepileptic effects? (2)
- Less energy getting to synapses for potassium and glutamate buffering (proepileptic)
- But also less energy for neurones to maintain synaptic activity (antiepileptic)
60
Give two dysfunctions of glutamate and GABA transport in astrocytes which may contribute to epilepsy. (2)
- Altered EAAT transporters
- Reduced glutamine synthetase
61
Describe how altered EAAT transporter activity in astrocytes may cause epilepsy. (2)
- Glutamate cannot be taken up into astrocyte as effectively
- Excess extracellular glutamate
62
Describe 2 ways in which reduced glutamine synthetase activity in astrocytes may contribute to epileptic activity. (2)
- Glutamate diffuses back out of EAAT transporters because they are bidirectional (glutamate would usually be converted to glutamine to prevent this)
- Less glutamine is transferred to inhibitory neurones and used to make GABA to stop epileptic activity
63
Describe what is meant by 'metabolic partitioning' in the brain. (1)
Neurones are dependent on astroglia for NT precursors (glutamine), energy (lactate), and antioxidants (glutathione).
64
Name the neuronal event which is proposed to be the original stimulus of epileptic behaviours. (1)
Paroxysmal depolarisation shift
65
Describe the paroxysmal depolarisation shift, in the context of epilepsy. (2)
An abnormal fluctuation in neuronal membrane voltage.
Does not last long but persists for longer than a normal AP.
66
Astrocytes express a wide range of NT receptors which are coupled to calcium signalling pathways.
How is the cell able to tell which NT bound to cause changes in calcium signalling? (1)
Frequency of calcium oscillations may encode information about the stimulus.
67
Describe two ways by which calcium signalling can spread throughout the astrocytic syncytium.
What is the consequence of this long range signalling mechanism in the context of epilepsy? (3)
- Diffusion of IP3 and calcium through gap junctions
- Extracellular release of ATP
- This may allow synchronicity between neurones
68
Describe a potential mechanism which may account for the neuronal synchronicity seen in epilepsy. (4)
- Neurone releases glutamate
- Glutamate binds to astrocyte and induces calcium signalling
- Calcium stimulates glutamate release from astrocytes
- Glutamate in extracellular space binds to NMDA receptors on multiple neurones and causes synchronous slow inward currents
69
Describe 3 pieces of evidence supporting the theory that astrocytes may be involved in epilepsy. (3)
HINTS:
1) Effects of epileptogenic agents
2) Photolytic release of astrocytic calcium
3) Anti-epileptic drug effects
1) Experimental epileptogenic agents increase calcium oscillations in astrocytes
2) Photolytic release of calcium within astrocytes causes depolarising shift
3) Common anti-epileptic drugs inhibit astrocyte calcium signalling
70
True or false? (1)
Epileptic activity is always associated with foci of reactive gliosis.
True
71
Describe three changes seen in REACTIVE astrocytes which may contribute to neuronal hyperexcitability and epileptic activity. (3)
- Redistributed K and AQP channels
- Decreased glutamine synthesis
- Increased glutamate release
72
Describe 'slow inward currents (SICs)'. (3)
- What are they?
- What causes them?
- What receptors are involved?
- Excitatory events in neurones
- Caused by astrocytic glutamate release
- And subsequent glutamate binding to neuronal extrasynaptic NMDA receptors
73
AP5 is an NMDA antagonist.
What would be the effect of adding this compound to neurones in the CA1 region of the hippocampus on slow inward currents? (1)
SICs will be inhibited
74
DHPG is a metabotropic glutamate receptor agonist.
TTX blocks sodium channels and inhibits synaptic transmission and action potentials.
What would be the effect on SICs of adding these two substances to a group of neurones? (1)
SICs would still be produced because they do not depend on synaptic transmission.
75
DHPG is a metabotropic glutamate receptor agonist.
If SICs are produced via NMDA receptors, how does adding DHPG to a sample of brain tissue cause slow inward currents in neurones? (3)
DHPG induces calcium oscillations in astrocytes.
Which stimulates release of astrocytic glutamate.
Which binds to NMDA receptors on neurones.
76
DHPG is a metabotropic glutamate receptor agonist.
Describe the temporal relationship you would expect to see in the calcium signalling between astrocytes and neurones if DHPG was added to a sample of brain tissue. (1)
Calcium would increase in astrocytes THEN neurones.
77
DHPG is a metabotropic glutamate receptor agonist.
AP5 is an NMDA antagonist.
Predict the effect on calcium oscillations in both astrocytes and neurones if both of these compounds were added to a sample of brain tissue. (2)
Astrocytic calcium oscillations would still occur.
Neuronal calcium oscillations would be blocked.
78
Describe what effect you would expect magnesium ions to have on neuronal slow inward currents. (1)
Reduced
79
Describe how astrocyte stimulation and SICs may contribute to the development of epilepsy. (2)
Astrocyte stimulation leads to slow inwards currents of neurones
in some cases, multiple neurones are stimulated simultaneously.
80
Explain why a low extracellular calcium may be able to trigger a rise in astrocytic calcium. (1)
In astrocytes, calcium is released from intracellular stores.
81
Why is there a delay between calcium oscillations in astrocytes and calcium oscillations in neurones? (2)
- Calcium has to trigger astrocytic glutamate release
- Glutamate has to bind to NMDA receptors on neurone
82
What demographic of people does Parkinson's disease usually affect? (1)
People over 50 yrs
83
Describe the typical symptom progression of Parkinson's disease. (1)
Symptoms gradually become worse over many years.
84
Give three symptoms of Parkinson's disease. (3)
- Tremor
- Rigidity
- Bradykinesia
85
Describe the typical tremor seen in Parkinson's disease. (2)
- When is it worse?
- What frequency?
Resting tremor which goes away with movement.
3-4 Hz
86
Symptoms of Parkinson's disease usually appear when what percentage of cells in the substantia nigra have been lost? (1)
80%
87
Dopaminergic cells in the substantia nigra are dying all the time. So why do most people not experience the symptoms of Parkinson's disease? (2)
Normal striatal dopamine decreases 5-7% per decade.
Normally the 80% threshold for Parkinson's symptoms would not be reached before death.
88
How is Parkinson's disease treated? (2)
L-dopa
plus a peripheral inhibitor of dopa decarboxylase
89
What does dopa decarboxylase do? (1)
Convert dopa to dopamine
90
Why is L-dopa given as a treatment for Parkinson's disease as opposed to dopamine? (1)
L-dopa can cross the BBB but dopamine can't
91
In Parkinson's disease, why does L-dopa have to be given with a peripheral inhibitor of dopa decarboxylase? (2)
To prevent conversion of L-dopa to dopamine in the bloodstream,
before it has had chance to cross the BBB.
92
Give six possible side effects of L-dopa therapy in Parkinson's disease. (6)
- Resistance (medication becomes less effective over time)
- Anxiety
- Excessive libido
- Hallucinations
- Narcolepsy
- Dyskinesia
93
In the past there have been cases of recreational drug users developing PD-like symptoms.
Name three of the drugs/drugs groups implicated. (3)
- Antipsychotics
- Heroin
- Fentanyl
94
Why can antipsychotics produce PD-like symptoms? (1)
They block dopamine
95
Why have heroin and fentanyl been able in the past to produce PD-like symptoms? (1)
Due to impurities when people started producing designer drugs.
96
In the past, a homemade batch of MPPP (a designer drug) contained an impurity which caused PD-like symptoms.
What was this impurity and how were the symptoms treated?
How did this impurity cause the symptoms. (2)
MPTP
Treated with L-dopa
The MPTP caused a massive loss of dopamine neurones in the substantia nigra.
97
After not knowing what caused Parkinson's disease, how did the discovery of MPTP help to fast-forward PD research? (1)
Could inject MPTP into animals to make animal models of Parkinson's disease.
98
What is MPTP, and what molecular properties make it a good model to produce symptoms of Parkinson's disease? (2)
MPTP is a selective neurotoxin.
It can cross the BBB and selectively destroy cells in the substantia nigra, which makes it a good model.
99
Is MPTP hydrophilic or lipophilic? (1)
Lipophilic
100
Describe the pathway which allows MPTP to kill cells in the substantia nigra once it has crossed the BBB. (8)
- MPTP taken up into astrocyte
- Converted to MPP+
- By monoamine oxidase B
- MPP+ released by astrocytes and taken up by neurones
- By dopamine uptake transporter
- MPP+ becomes concentrated in mitochondria
- Where it inhibits complex 1
- Which results in reduced ATP production, free radical generation, and cell death
101
The effects of MPP+ suggest that mitochondrial dysfunction may be involved in the aetiology of PD.
Is this supported by studies? (1)
Yes - deficits in mitochondrial NADH CoQ1 reductase (complex 1) have been reported in PD patients
102
Pesticides are an environmental risk factor for Parkinson's disease.
Give two ways that MPTP may help explain how pesticides can lead to Parkinson's disease. (2)
- Paraquat, a widely used herbicide, differs from MPP+ by only 1 methyl group
- Rotenone, a naturally occurring herbicide, inhibits mitochondrial complex 1
103
Pargyline (an MAO-B inhibitor) has been used in clinical trials for PD.
What effect might this have on the development of Parkinson's disease and why? (2)
Delay PD onset
because it stops MAO-B converting MPTP into MPP+ (its active form)
104
How may the basal ganglia be manipulated to improve PD symptoms? (1)
Deep brain stimulation of STN
