Disease studied in session 1

Question 1

clinical representation of demyelinating diseases

Answer 1

depending on whre myelin is attacked, display different neurological symptoms

Question 2

models to study demyelination

Answer 2

i) experimental autoimmune encephalomyelitis (EAE)
ii) cuprizone
iii) lysolecithin (LPC

Question 3

How does LPC work?

Answer 3

kill specific oligodendrocyte on site of injection

Question 4

how does EAE work?

Answer 4

immune system in mice attacks myelin present randomly (no control over where the attack occurs)

Question 5

types of stroke

Answer 5

i) ischemic (blockage of vessels)
ii) hemorrhagic (leakage of blood)

Question 6

focal models for ischemic stroke

Answer 6

i) photothrombosis
ii) endothelin-1

Question 7

how does photothrombosis work?

Answer 7

inject small molecule
–> vessels constrict and stroke occurs in that area

Question 8

how does endothelin-1 work?

Answer 8

small peptide that causes constriction of vessels where it resides

Question 9

widespread model for ischemic stroke

Answer 9

artery occulsion

Question 10

how did ppl study recruitment of NSC in human V-SVZ?

Answer 10

immunostaining Ki67 for dividing cells, PSA-NCAM for neuroblast
–> see greater proliferation of NSC, neuroblast after ischemic injury

Question 11

What happens after V-SVZ is activated in stroke models?

Answer 11

most new neurons cannot survive and response is short-lived

Question 12

where does AD pathology first found?

Answer 12

entorhinal cortex (EC)
–> gateway to and from hippocampus

Question 13

how does alzheimers disease develop?

Answer 13

i) amyloid beta forms plaques (outside of cell) –> impair neuronal function
ii) tau aggregates into neurofibrillary tangles (NFT) inside of cell

Question 14

where are amyloid plaques found?

Answer 14

outside of cell

Question 15

where are neurofibrillary tangles (NFT) found?

Answer 15

inside of cell
–> impair microtubule dependent process

Question 16

describe results from using mice model for AD

Answer 16

use BrdU for labelling
–> way less BrdU + cells in mutant
–> less proliferation or survival of SGZ NSC

Question 17

findings from human brain tissue of AD patient

Answer 17

with mRNA seq
–> fewer immature granule cells in AD brain
–> reduced neurogensis in AD

Question 18

Transplantation studies for Parkinson’s disease

Answer 18

i) implant dopamine neurons into mice model
–> shown improvement
ii) allogenic transplant of dopamine progenitor cells (from iPSC) in patient
–> only one patient tho
iii) meta-analysis
–> NSC transplant improve cognition, lower amyloid beta deposition
iv) transplant human fetal NSC to hippocampus
–> no engraftment, but see reduced amyloid beta deposition

Question 19

Drugs used to recruit NSC

Answer 19

metformin (diabetes drug)