Lecture 22 - Neuropathology

Question 1

what 3 things could go wrong in synaptopathies

Answer 1

• neurotrans synthesis or release
• pre syn vesicles/ machinery
• signalling, expression and function of post syn receptors

Question 2

how can ltd and ltp affect synaptic function

Answer 2

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

Question 3

what could synaptopathies result from

Answer 3

• genetics
• drug use
• ageing
• viral infections

Question 4

what 4 things could synaptopathies cause

Answer 4

• abnormal density and morphology of dendritic spines
• poor synaptic signalling and plasticity
• synapse loss
• neuronal death

Question 5

an example of synaptopathies

Answer 5

epilepsy
(possibly, cuz could have other causes)

Question 6

what can inc risk of developing epiliepsy

Answer 6

infection
stroke
brain injurty

Question 7

what goes wrong in synapse to cause epilipsy

Answer 7

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

Question 8

what are the 3 epilepsy treatments and what do they target

Answer 8

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

Question 9

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

Answer 9

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

Question 10

what is typical origin of channelopathies

Answer 10

genetic or autoimmune

Question 11

what may channelopathies lead to

Answer 11

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

Question 12

how might channelopathies cause convulsions (epilepsy)

Answer 12

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

Question 13

what might mutations in GRIN2B cause

Answer 13

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

Question 14

what is myotonia congenita caused by and the effects

Answer 14

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

Question 15

what is malignant hyperthermia caused by

Answer 15

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

Question 16

what can malig hyper cause

Answer 16

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

Question 17

what are some common triggers for malignant hyperthermia

Answer 17

anaesthesia
overheating after excericise

Question 18

3 main types of glial cells in brain

Answer 18

astrocytes
microglia
oligodendrocytes

Question 19

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

Answer 19

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

Question 20

how can astroglial reactivity help

Answer 20

preserves neural tissue
isolates lesioned area from rest of brain

Question 21

what can cause astrodegeneration and what does it cause

Answer 21

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

Question 22

3 functional stages of microglia

Answer 22

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

Question 23

Functions of each stage of microglia

Answer 23

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

Question 24

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

Answer 24

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

Question 25

what disease can be caused by dysfunctional oligodendrovytes

Answer 25

multiple sclerosis
impaired conductance and nerve damage

Question 26

symptoms of multiple sclerosis

Answer 26

• limb weakness
• electric shock sensations
• tremor
• vision problems
• fatigue, dizziness

Question 27

in diseases like encephalitis and MS, what is a cause of inflammation

Answer 27

immune cells e.g. leukocytes invading the CNS

Question 28

in neurodegen diseases what is a cause of inflammation

Answer 28

microglial cells and astrocytes secreting too much cytokines

Question 29

along with cytokines, what else is produced in neuroinflamm

Answer 29

reactive oxygen species
e.g. peroxide

Question 30

what can reactive oxygen species cause

Answer 30

• rearrangement of postsyn glutamate receptors
• imparied hippocampal LTP
• axonal and dendritic loss

Question 31

what is the BB barrier function

Answer 31

sealed cell to cell contacts via tight junctions
allowing separation of blood and brain compartments

Question 32

what things are needed so that drugs can be delivered through BBB

Answer 32

• healthy blood vessels
• good blood flow
• active transport systems, cuz no other way for drug to get across

Question 33

what happens when BBB breaks down

Answer 33

• inc vascular permeability
• so bad stuff from blood enters brain
• causing inflamm responses
• and neuronal injury, synaptic dysfunction, neurodegen

Question 34

how can drug delivery be impaired if the BBB breaks down

Answer 34

• solute transport no good
• bad flow of interstitial fluid
• active transport systems no good
• so drugs get trapped in perivascular spaces