ELM22: Neuropathology

Question 1

What are synaptopathies?

Answer 1

Brain disorders caused by synaptic dysfunction

Question 2

What are the three different mechanisms of synaptopathies?

Answer 2

Alterations in NT synthesis of release
Alterations in pre-synaptic vesicle machinery
Alterations in signalling expression and function of post synaptic NT receptors

Question 3

What effect does LTP have on dendritic spine size?

Answer 3

Increased spine size

Question 4

What effect does LTD on dendritic spine size?

Answer 4

Decreased spine size

Question 5

What does dendritic spine size effect?

Answer 5

Post synaptic density
Number of glutamate receptors
Synaptic strength

Question 6

What can occur in the brain due to morphological changes in dendritic spines?

Answer 6

Cognitive alterations
Neuropyschiatric disease

Question 7

What are some causes of synaptopathies?

Answer 7

Genetics
Drug use
Aging
Viral infections

Question 8

What can synaptopathies lead to?

Answer 8

Abnormal dendritic spine density and morphology
Synapse loss
Neuronal death
Aberrant synaptic signalling and plasticity

Question 9

What is thought to be the cause of epilepsy?

Answer 9

Imbalance of excitatory and inhibitory circuits

Question 10

What is thought to be the mechanism resulting in epileptic seizures?

Answer 10

1. Enhanced glutamatergic neurotransmission and decreased GABA release
2. Increase in excitatory neurotransmission
3. Seizure episodes

Question 11

What is Levetiracetam as a treatment for epilepsy?

Answer 11

Reduces NT release at glutaminergic synapses

Question 12

What is Valproate as a treatment for epilepsy?

Answer 12

Increased amount of inhibitory GABA

Question 13

What is Phenytoin as a treatment for epilepsy?

Answer 13

Prolongs Na+ channel inactivation

Question 14

What are channelopathies?

Answer 14

Group of disorders caused by dysfunction of ion channels

Question 15

How can channelopathies cause convulsions?

Answer 15

1. Abnormal calcium and potassium channels in the brain
2. Repolarisation defects
3. Convulsions

Question 16

What is GRIN2B?

Answer 16

Gene encoding NR2B
NR2B is involved in glutamate binding

Question 17

What occurs due to a gain of function mutation in GRIN2B?

Answer 17

Hyperexcitability
Causes seizures

Question 18

What occurs due to a loss of function mutation in GRIN2B?

Answer 18

Hypoexcitability
Causes learning difficulties and neurodevelopmental problems

Question 19

What are the three main types of glia in the brain?

Answer 19

Astrocytes
Microglia
Oligodendrocytes

Question 20

What is the function of astrocytes?

Answer 20

Structural
Metabolic sensing
Repair and modulation synapse transmission

Question 21

What is astrocyte reactivity?

Answer 21

Hypertrophy and proliferation
Caused neuroprotection

Question 22

What is astrodegeneration?

Answer 22

Atrophy and functional asthenia
Causes neurotoxicity

Question 23

What is the function of microglia?

Answer 23

Immune defence of the CNS

Question 24

What is the nurturer state of microglia?

Answer 24

Highly ramified and evenly spaced
Maintain milieu homeostasis
Synaptic remodelling and migration
Remove apoptotic neurons

Question 25

What is the sentinel state of microglia?

Answer 25

Abundant processes In motion Surveillance and sensing

Question 26

What is the warrior state of microglia?

Answer 26

Stocky and less ramified Defence against pathogens and injurious self proteins

Question 27

How can microglia cause further neurodegeneration?

Answer 27

1. Disease stimulus 2. Sensing and host defence 3. Dysregulation due to host defence 4. Exaggerated proinflammatory response and neurodegeneration

Question 28

What is the function oligodendrocytes?

Answer 28

Formation of myelin

Question 29

What are the symptoms of multiple sclerosis?

Answer 29

Limb numbness and weakness Electric shock sensations Tremor Fatigue and dizziness

Question 30

What is the cause of neuroinflammation in encephalitis and MS?

Answer 30

Invading immune cells

Question 31

What is the cause of neuroinflammation in neurodegenerative processes?

Answer 31

CNS resident cells

Question 32

What are four features of neuroinflammation?

Answer 32

1. Increased production of cytokines and reactive oxygen species 2. Molecular rearrangement of postsynaptic glutamate receptors 3. Impairment of hippocampal LTP 4. Axonal and dendritic loss

Question 33

What is the blood brain barrier?

Answer 33

Continuous endothelial membrane of the brain vasaculature

Question 34

What is the function of the blood brain barrier?

Answer 34

Separate circulating blood and brain compartments Regulate blood to brain

Question 35

What is needed for delivery of drugs?

Answer 35

Healthy blood vessels Normal formation of blood vessels Adequate blood flow Recruitment of active transport systems

Question 36

How does the breakdown of the blood brain barrier promote neurodegeneration

Answer 36

Increased vascular permeability Toxic blood derived molecules cells and microbial agents enter brain Inflammatory and immune responses Neuronal injury synaptic dysfunction loss of neurons loss of brain connectivity

Question 37

What are the features of blood brain barrier disruption in alzheimers disease?

Answer 37

Brain capillary leakages Pericyte degeneration Endothelial degeneration Cellular infiltration

Question 38

What are the features of blood brain barrier disruption in parkinsons disease?

Answer 38

Brain capillary leakages Endothelial degeneration Cellular infiltration

Question 39

What are the features of BBB disruption in huntingdons disease?

Answer 39

Brain capillary leakages Endothelial degeneration

Question 40

What are the features of BBB disruption in MS?

Answer 40

Brain capillary leakages Endothelial degeneration Cellular infiltration

Question 41

What are some causes of impaired drug delivery when the BBB breaks down?

Answer 41

Impaired solute transport Diminished ISF regional flow Decreased function and AT systems Drugs trapped in enlarged perivascular spaces