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Excitable Cells > ELM22: Neuropathology > Flashcards

ELM22: Neuropathology Flashcards

1
Q

What are synaptopathies?

A

Brain disorders caused by synaptic dysfunction

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2
Q

What are the three different mechanisms of synaptopathies?

A

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

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3
Q

What effect does LTP have on dendritic spine size?

A

Increased spine size

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4
Q

What effect does LTD on dendritic spine size?

A

Decreased spine size

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5
Q

What does dendritic spine size effect?

A

Post synaptic density
Number of glutamate receptors
Synaptic strength

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6
Q

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

A

Cognitive alterations
Neuropyschiatric disease

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7
Q

What are some causes of synaptopathies?

A

Genetics
Drug use
Aging
Viral infections

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8
Q

What can synaptopathies lead to?

A

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

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9
Q

What is thought to be the cause of epilepsy?

A

Imbalance of excitatory and inhibitory circuits

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10
Q

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

A
  1. Enhanced glutamatergic neurotransmission and decreased GABA release
  2. Increase in excitatory neurotransmission
  3. Seizure episodes
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11
Q

What is Levetiracetam as a treatment for epilepsy?

A

Reduces NT release at glutaminergic synapses

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12
Q

What is Valproate as a treatment for epilepsy?

A

Increased amount of inhibitory GABA

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13
Q

What is Phenytoin as a treatment for epilepsy?

A

Prolongs Na+ channel inactivation

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14
Q

What are channelopathies?

A

Group of disorders caused by dysfunction of ion channels

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15
Q

How can channelopathies cause convulsions?

A
  1. Abnormal calcium and potassium channels in the brain
  2. Repolarisation defects
  3. Convulsions
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16
Q

What is GRIN2B?

A

Gene encoding NR2B
NR2B is involved in glutamate binding

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17
Q

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

A

Hyperexcitability
Causes seizures

18
Q

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

A

Hypoexcitability
Causes learning difficulties and neurodevelopmental problems

19
Q

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

A

Astrocytes
Microglia
Oligodendrocytes

20
Q

What is the function of astrocytes?

A

Structural
Metabolic sensing
Repair and modulation synapse transmission

21
Q

What is astrocyte reactivity?

A

Hypertrophy and proliferation
Caused neuroprotection

22
Q

What is astrodegeneration?

A

Atrophy and functional asthenia
Causes neurotoxicity

23
Q

What is the function of microglia?

A

Immune defence of the CNS

24
Q

What is the nurturer state of microglia?

A

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

25
Q

What is the sentinel state of microglia?

A

Abundant processes In motion Surveillance and sensing

26
Q

What is the warrior state of microglia?

A

Stocky and less ramified
Defence against pathogens and injurious self proteins

27
Q

How can microglia cause further neurodegeneration?

A
  1. Disease stimulus
  2. Sensing and host defence
  3. Dysregulation due to host defence
  4. Exaggerated proinflammatory response and neurodegeneration
28
Q

What is the function oligodendrocytes?

A

Formation of myelin

29
Q

What are the symptoms of multiple sclerosis?

A

Limb numbness and weakness Electric shock sensations
Tremor
Fatigue and dizziness

30
Q

What is the cause of neuroinflammation in encephalitis and MS?

A

Invading immune cells

31
Q

What is the cause of neuroinflammation in neurodegenerative processes?

A

CNS resident cells

32
Q

What are four features of neuroinflammation?

A
  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
33
Q

What is the blood brain barrier?

A

Continuous endothelial membrane of the brain vasaculature

34
Q

What is the function of the blood brain barrier?

A

Separate circulating blood and brain compartments
Regulate blood to brain

35
Q

What is needed for delivery of drugs?

A

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

36
Q

How does the breakdown of the blood brain barrier promote neurodegeneration

A

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

37
Q

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

A

Brain capillary leakages
Pericyte degeneration
Endothelial degeneration
Cellular infiltration

38
Q

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

A

Brain capillary leakages
Endothelial degeneration
Cellular infiltration

39
Q

What are the features of BBB disruption in huntingdons disease?

A

Brain capillary leakages
Endothelial degeneration

40
Q

What are the features of BBB disruption in MS?

A

Brain capillary leakages
Endothelial degeneration
Cellular infiltration

41
Q

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

A

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

Excitable Cells (23 decks)

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