Lecture 22 - Neuropathology Flashcards

1
Q

what 3 things could go wrong in synaptopathies

A
  • neurotrans synthesis or release
  • pre syn vesicles/ machinery
  • signalling, expression and function of post syn receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how can ltd and ltp affect synaptic function

A

can change dendritic spine size
(LTP = increase, LTD = decrease)
which correlates w/ synaptic strength

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what could synaptopathies result from

A
  • genetics
  • drug use
  • ageing
  • viral infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what 4 things could synaptopathies cause

A
  • abnormal density and morphology of dendritic spines
  • poor synaptic signalling and plasticity
  • synapse loss
  • neuronal death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

an example of synaptopathies

A

epilepsy
(possibly, cuz could have other causes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what can inc risk of developing epiliepsy

A

infection
stroke
brain injurty

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what goes wrong in synapse to cause epilipsy

A

glutamatergic trans increased but GABA decreased
- so too much excitatory stuff

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the 3 epilepsy treatments and what do they target

A

Leve = reduce glutamatergic neurotrans release
Val = inc GABA
Phen = prolong inactivation of Na+ channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what could be some issues caused by inherited epilepsy in the synapse

A

mutated ion channels (channelopathies ig?)
- GABA receptors
- Kv channels
- Nav channels
- Cl channels
- ACh rec

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is typical origin of channelopathies

A

genetic or autoimmune

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what may channelopathies lead to

A

epilepsy, migraine, ataxia (lack of movement control), paralysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

how might channelopathies cause convulsions (epilepsy)

A

abnormal K+ and Ca2+ channels can cause repolarisation defects
so prolonged depol leads to seizures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what might mutations in GRIN2B cause

A

abnormality in NR2B which is a subunit of NMDA receptor (for glutamate)
either gain or loss of function
so either seizures or neurodevelopment problems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is myotonia congenita caused by and the effects

A

caused by mutated Cl- channel
causes muscle weakness after contraction
goats collapsing, but humans too

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is malignant hyperthermia caused by

A

mutated ryanodine receptor
so an excessive release of Ca2+ from SR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what can malig hyper cause

A

short term = muscles contract, become rigid, high fever, fast heart rate
long term = rhabdomyolysis and high + levels

17
Q

what are some common triggers for malignant hyperthermia

A

anaesthesia
overheating after excericise

18
Q

3 main types of glial cells in brain

A

astrocytes
microglia
oligodendrocytes

19
Q

what can increase in astroglial reactivity cause and what is it caused by

A

caused by brain injury and stroke
hypertrophy and proliferation (so, thicker astrocytes w/ more processes)

20
Q

how can astroglial reactivity help

A

preserves neural tissue
isolates lesioned area from rest of brain

21
Q

what can cause astrodegeneration and what does it cause

A

caused by: neurodegen diseases or psych disorders
atropy
functional asthenia (weakness)
decreased cell size and processes

22
Q

3 functional stages of microglia

A
  1. nurturer - lots branches, even spaced
  2. sentinal - lots long branches, in motion
  3. warrior - stocky, less branches, accumulate
23
Q

Functions of each stage of microglia

A

Nurturer:

this state maintains homeostasis, is involved in synaptic remodelling and migration and removes apoptotic neurons.

Sentinel:

this state is involved in surveillance and sensing

Warrior:

this state defends against pathogens and removes pathological proteins such as amyloid beta

24
Q

what might cause micorglia to not do its job and cause exaggerated responses

A

persistant pathogological stimuli
e.g. tau, HTT (from hungtintons_

25
what disease can be caused by dysfunctional oligodendrovytes
multiple sclerosis impaired conductance and nerve damage
26
symptoms of multiple sclerosis
- limb weakness - electric shock sensations - tremor - vision problems - fatigue, dizziness
27
in diseases like encephalitis and MS, what is a cause of inflammation
immune cells e.g. leukocytes invading the CNS
28
in neurodegen diseases what is a cause of inflammation
microglial cells and astrocytes secreting too much cytokines
29
along with cytokines, what else is produced in neuroinflamm
reactive oxygen species e.g. peroxide
30
what can reactive oxygen species cause
- rearrangement of postsyn glutamate receptors - imparied hippocampal LTP - axonal and dendritic loss
31
what is the BB barrier function
sealed cell to cell contacts via tight junctions allowing separation of blood and brain compartments
32
what things are needed so that drugs can be delivered through BBB
- healthy blood vessels - good blood flow - active transport systems, cuz no other way for drug to get across
33
what happens when BBB breaks down
- inc vascular permeability - so bad stuff from blood enters brain - causing inflamm responses - and neuronal injury, synaptic dysfunction, neurodegen
34
how can drug delivery be impaired if the BBB breaks down
- solute transport no good - bad flow of interstitial fluid - active transport systems no good - so drugs get trapped in perivascular spaces