SB L3 - Neurogenesis part 2 Flashcards
PTSD brain anatomy shows?
decreased hippocampal volume
- is this because we are not making new cells or due to cell death/atrophy/less branching?
What is the effect of antidepressants and ECT on neurogenesis?
stimulates it
both proliferation and survival
Another labeling technique similar to BrdU?
3H[thyamine]
Prolonged stress brain anatomy shows?
decreased hippocampal neurogenesis
Proposed mechanism of why there is less hippocampal neurogenesis in MDD?
cortisol is elevated in MDD - negatively regulates neurogenesis
Antidepressants and neurogenesis actuely vs chronically?
If you look at the Fluoxetine data not much happens after a day but chronically you get a significant increase in cells.
Is this why 4-6 weeks to effect?
SSRIs require….. receptor for neurogensis
5ht1a
Describe novelty supressed feeding task
paradigm where you have five days where you train them to eat something yummy for three days, they learn that it’s nice. On the fours day you do a test to see how long it takes them to approach the thing theyve learnt is yummy. Then you put them in a sparse bright cage (aversive environment). So there is a conflict between the two so the approach is always longer, so you look at latency.
What does novelty supressed feeding show with antidepressants?
with antidepressants in 5HT1A KO?
All antidepressants reduce the time to feed.
In KO 5HT1A animals are anxious and there is latency to feed. Imipramine (TCA so not selective to serotonin) and some others are not affected.
5HT1A KO and fluorextine showed…. (2)?
Ref
- KO mice are selectively insensitive to the behavioural effects of fluoxetine in a novelty- suppressed feeding task
- KO mice are selectively insensitive to the neurogenic effects of fluoxetine
Effect of ECS (what even is this) on mRNAs in the hippocampus?
upregulates BDNF, Trk B and VEGF mRNAs
Effects of SSRIs, TCAs, MAOIs, on mRNA in the hippocampus?
increasews BDNF
How does antidepressant treamtents affect autophosphyrylation of TrkB?
increased - constitutatively activates the pathway bypassing BDNF
Overall effect of stress on:
a. gulcoricoids
b. VEGF
c. neurogenesis
increased GC
decresed VEGF =
decreased neurogenesis
over all effect of antidepressant therapy on
a. neurotransmitters (2)
b. VEGF
c. BDNF
d. neurogenesis
increased NE and 5HT
increased VEGF
increased BDNF
increased neurogenesis
over all effect of antidepressant therapy on
a. neurotransmitters (2)
b. VEGF
c. BDNF
d. neurogenesis
increased NE and 5HT
increased VEGF
increased BDNF
increased neurogenesis
BDNF levels are ………………….. in postmortum depressed pt
decreased
How do antidepressants effect BDNF levels?
restore them (increase)
A SNP in BDNF is associated with ……. and ……
memory impairments and mood disorders
- The substitution is present in the pro gene that needs to be cleaved to make the BDNF.
- Carriers of the mutation have a smaller hippocamul volume.
BDNF Val66Met mice show
ref
Increased anxiety-related behaviour that is resistant to treatment with fluoxetine (in terms of percentage of time in closed areas)
Chen et al. Science 2006
BDNF Val66Met mice show
ref
Increased anxiety-related behaviour that is resistant to treatment with fluoxetine (in terms of percentage of time in closed areas)
Chen et al. Science 2006
Why might making a small molecule netrophic factor drug be a poor therapeutic target? (3)
id you inject it into the brain it just stats where it is. Could use s/c.
Stumulates growth of many things - cancer?
Must ensure it can cross the BBB
There is debate about whether nerogenesis is ……. or …… of depression
cause or consequence
-maybe you get impaired neurogen from genes/envirmonent making you vulnerable to disorders. Does this matter when treating as all antidepressants affect it?
Antidepressant effects can be abolised by
ref
x-ray hippocampal irradiation - in some behavioural paradigms but not in others
