1. FGF2 blocks PTSD symptoms via an astrocyte-based mechanism
Presented by Justin P. Smith

2. FGF2
Growth factor, protein or steroid hormone, that regulating cell proliferation, differentiation, and survival
22 FGF ligands
4 FGF receptors in rodents,
5 FGF receptors in humans
Single chain polypeptide protein
FGF2 has contributed significantly:
Mechanisms neuronal proliferation, survival, and repair

3. Roles of FGF2 Alter structure of hippocampus
regulating cell proliferation, morphology
increasing synaptic efficiency
modulates several of the molecules in LTP and memory
formation and/or consolidation of extinction memories
Other roles?

5. CS- white noise; level in the chambers was increased by 8 dB during CS
Fibroblast Growth Factor-2 Enhances Extinction and Reduces Renewal of Conditioned Fear
Conditioned Fear
CS- white noise; level in the chambers was increased by 8 dB during CS
US- 0.6 mA, 1.0 s footshock
FGF2, subcutaneously after the last extinction trial
Renewal-extinguished CS is presented in the original fear conditioning context, or in a completely novel context, the animal will express recovered levels of fear

6. Fig. 1: FGF2 facilitates long-term extinction and needs
to be administered at a dose no less than 20 ng/g of body
weight to be effective

7. Fig. 2: FGF2 significantly reduced renewal after
extinction, even when the levels of CS-elicited freezing in
the vehicle and FGF2-treated rats tested in the extinction
context were equated

8. FGF2 may change quality of extinction,
Fig. 3: FGF2 significantly reduced renewal after extinction even
when the time spent in the extinction context was equated
between FGF2- and vehicle-treated rats
FGF2 may change quality of extinction,
possibly weakening the original fear memory

9. Main Paper Intro Cellular mechanism for PTSD not fully understood
Role of astrocytes in mood disorders
Largest population in hippocampus
FGF2
Synthesized in astrocytes
Modulates adult rat hippocampal neurogenesis
enhances long-term extinction of fear memory & reduces reinstatement

10. Methods ♂ Sprague-Dawley rats (180-200g) Single Prolonged Stress (SPS)
12:12 light dark (lights off at?)
Single Prolonged Stress (SPS)
1) restrained for 2 h
2) 20 min forced swimming
15-min recuperation
3) ether exposure until general anesthesia (<5 min)

11. Behavioral Tests Open Field (OF) Elevated Plus Maze (EPM)
Conditioned Fear

12. Brain Regions
Anterior Cingulate Cortex-reward anticipation, decision-making, impulse control, and emotion

14. CS+: test for conditioned fear response to shock chamber;
Fig. 2
FGF2 ↓ enhanced fear response in the conditioned fear extinction and sensitized fear tests
CS+: test for conditioned fear response to shock chamber;
CSn: test for sensitized fear response to neutral tone in a neutral context

15. Fig. 3: OF
Fig. 3 Open Field

16. Fig. 4 EPM

17. Fig. 5:
SPS inhibited the astrocytic action
FGF2 application from SPS day 7 to 10 activated GFAP immunodensities to normal levels

18. Fig. 6: 3-D reconstruction of FGF2 on GFAP expression in hippocampus induced by SPS

19. Fig. 7 Effects of i.p. admin of FGF2 on GFAP and NeuN expression in hippocampus of SPS rats

20. Take home GFAP ↓ in SPS FGF2 rescue effect
↓ Anxiety and freezing behavior
FGF2 possible therapeutic for PTSD
Astrocyte role in PTSD
Astrocytes may be underlying the mechanisms of PTSD?!?