Lecture 22 - Neuropathology Flashcards
what 3 things could go wrong in synaptopathies
- neurotrans synthesis or release
- pre syn vesicles/ machinery
- signalling, expression and function of post syn receptors
how can ltd and ltp affect synaptic function
can change dendritic spine size
(LTP = increase, LTD = decrease)
which correlates w/ synaptic strength
what could synaptopathies result from
- genetics
- drug use
- ageing
- viral infections
what 4 things could synaptopathies cause
- abnormal density and morphology of dendritic spines
- poor synaptic signalling and plasticity
- synapse loss
- neuronal death
an example of synaptopathies
epilepsy
(possibly, cuz could have other causes)
what can inc risk of developing epiliepsy
infection
stroke
brain injurty
what goes wrong in synapse to cause epilipsy
glutamatergic trans increased but GABA decreased
- so too much excitatory stuff
what are the 3 epilepsy treatments and what do they target
Leve = reduce glutamatergic neurotrans release
Val = inc GABA
Phen = prolong inactivation of Na+ channels
what could be some issues caused by inherited epilepsy in the synapse
mutated ion channels (channelopathies ig?)
- GABA receptors
- Kv channels
- Nav channels
- Cl channels
- ACh rec
what is typical origin of channelopathies
genetic or autoimmune
what may channelopathies lead to
epilepsy, migraine, ataxia (lack of movement control), paralysis
how might channelopathies cause convulsions (epilepsy)
abnormal K+ and Ca2+ channels can cause repolarisation defects
so prolonged depol leads to seizures
what might mutations in GRIN2B cause
abnormality in NR2B which is a subunit of NMDA receptor (for glutamate)
either gain or loss of function
so either seizures or neurodevelopment problems
what is myotonia congenita caused by and the effects
caused by mutated Cl- channel
causes muscle weakness after contraction
goats collapsing, but humans too
what is malignant hyperthermia caused by
mutated ryanodine receptor
so an excessive release of Ca2+ from SR
what can malig hyper cause
short term = muscles contract, become rigid, high fever, fast heart rate
long term = rhabdomyolysis and high + levels
what are some common triggers for malignant hyperthermia
anaesthesia
overheating after excericise
3 main types of glial cells in brain
astrocytes
microglia
oligodendrocytes
what can increase in astroglial reactivity cause and what is it caused by
caused by brain injury and stroke
hypertrophy and proliferation (so, thicker astrocytes w/ more processes)
how can astroglial reactivity help
preserves neural tissue
isolates lesioned area from rest of brain
what can cause astrodegeneration and what does it cause
caused by: neurodegen diseases or psych disorders
atropy
functional asthenia (weakness)
decreased cell size and processes
3 functional stages of microglia
- nurturer - lots branches, even spaced
- sentinal - lots long branches, in motion
- warrior - stocky, less branches, accumulate
Functions of each stage of microglia
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
what might cause micorglia to not do its job and cause exaggerated responses
persistant pathogological stimuli
e.g. tau, HTT (from hungtintons_
what disease can be caused by dysfunctional oligodendrovytes
multiple sclerosis
impaired conductance and nerve damage
symptoms of multiple sclerosis
- limb weakness
- electric shock sensations
- tremor
- vision problems
- fatigue, dizziness
in diseases like encephalitis and MS, what is a cause of inflammation
immune cells e.g. leukocytes invading the CNS
in neurodegen diseases what is a cause of inflammation
microglial cells and astrocytes secreting too much cytokines
along with cytokines, what else is produced in neuroinflamm
reactive oxygen species
e.g. peroxide
what can reactive oxygen species cause
- rearrangement of postsyn glutamate receptors
- imparied hippocampal LTP
- axonal and dendritic loss
what is the BB barrier function
sealed cell to cell contacts via tight junctions
allowing separation of blood and brain compartments
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
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
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
