Week 7

Question 1

Stress kills
Stress and anti-depressants have opposing
effects on:
1. ** in the ** of the **
2. Production of ** and ** in the
** and **
VEGF increases **
BDNF increases **

Answer 1

Stress kills
Stress and anti-depressants have opposing
effects on:
1. Neurogenesis in the SGZ of the dentate
gyrus
2. Production of VEGF and BDNF in the
cortex and hippocampus
VEGF increases proliferation in SGZ
BDNF increases neuronal survival

Question 2

1. The family of neurotrophins
   * Synthesized as ** (~** AA) and then processed to ** long **
   * ** as the prototypical growth factor
   a) Maintains **, causes ** (previous in vitro assay)
   b) Not required in **
   * Brain-Derived Neurotrophic Factor (BDNF)
   a) ~% homology with **; purified from **
   * Neurotrophins: ** and **
   a) **-based cloning
2. Neurotrophins & their receptors
   a) p75LNTR: **; interestingly homology to **
   Trk: ** (not **)

Answer 2

1. The family of neurotrophins
   * Synthesized as precursors (~250 AA) and then processed to 100-120 AA long proteins
   * NGF as the prototypical growth factor
   * Maintains cell survival, causes neurite outgrowth (previous in vitro assay)
   * Not required in CNS
   * Brain-Derived Neurotrophic Factor (BDNF)
   * ~50% homology with NGF; purified from pig brains
   * Neurotrophins: NT-3 and NT-4/5
   * PCR-based cloning
2. Neurotrophins & their receptors
   a) p75LNTR: Low affinity; interestingly homology to TNFR
   Trk: tropomyosin-related kinase (not tyrosine kinase receptor)

Question 3

1. BDNF – potentiation story
   * Stronger presynaptic input produces **
   * BDNF release in turn activates ** and **
   * **/ and ** generation (signaling molecule?)
   * Synapses and LTP implications?
2. Healthy brains need BDNF- or do they?
   * Identification of a ** in the BDNF gene - **
   * Decreased secretion/release of BDNF resulting in **, reduced** as well as **
   * Blocking normal BDNF signaling using ** antibodies reduces **, and reduces **and ** (such as the NCAM- 180 and N-cadherin, AMPA receptor complexes etc.)
   * Appears to be particularly important in the **

Answer 3

1. BDNF – potentiation story
   * Stronger presynaptic input produces greater release including BDNF
   * BDNF release in turn activates post- synaptic growth and AMPAR stability
   * Synthesis/stabilization and nNOS generation (signaling molecule?)
   * Synapses and LTP implications?
2. Healthy brains need BDNF- or do they?
   * Identification of a polymorphism in the BDNF gene - Met66Val
   * Decreased secretion/release of BDNF resulting in specific areas of reduction, reduced episodic memory function as well as increased anxiety and depression
   * Blocking normal BDNF signaling using anti-TrkB antibodies reduces numbers of synapses, and reduces exercise-mediated
   increases in memory and synaptic proteins (such as the NCAM- 180 and N-cadherin, AMPA receptor complexes etc.)
   * Appears to be particularly important in the hippocampus

Question 4

Why controls in science are important
* Originally examining the relationship
between the ** genotype and
**
* Found that ** look at the data!
* In fMRI imaging studies also showed
that having Met/Val ** than ** (smaller
cohort studies)

Answer 4

Why controls in science are important
* Originally examining the relationship
between the Met66 genotype and
schizophrenia
* Found that there was a significant
reduction in hippocampal dependent
memory – look at the data!
* In fMRI imaging studies also showed
that having Met/Val performed worse
in recall tests than Val/Val (smaller
cohort studies)

Question 5

Measuring synaptic “health”
* How do you test for health of synapses and neurons in the hippocampus
* Have to rely on that can be picked up **or **
* In this case the marker – ** (**) was found to be lower in ** vs. ** subjects

Answer 5

Measuring synaptic “health”
* How do you test for health of synapses and neurons in the hippocampus
* Have to rely on having a marker that can be picked up via MRI or MRS
* In this case the marker – NAA (N-Acetyl –Aspartate) was found to be lower in Val/Met vs. Val/Val subjects

Question 6

Visualization Methods-3H-MRS
* Magnetic resonance spectroscopy (MRS) really cool new technique that measures ** (not
**)
* Typically examine molecules such as **, and **
* It’s really exactly like the ** you would do in chemistry – done on a **that can be **as in the next example
- MRS used to measure **of ** and ** ( – normalized against **)
- Creatinine levels used because of
**and it has been shown
to be **

Answer 6

Visualization Methods-3H-MRS
* Magnetic resonance spectroscopy (MRS) really cool new technique that measures protons in other biomaterials (not
water)
* Typically examine molecules such as N-acetylaspartate, and creatinine
* It’s really exactly like the proton spectroscopy you would do in chemistry – done on a small volume of the brain that can be spatially localized as in the next example
- MRS used to measure health status of individual brain regions and neurons (NAA levels – normalized against creatinine)
- Creatinine levels used because of
characteristic peak and it has been shown
to be relatively constant in the brain