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

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

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?

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

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

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

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

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

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)

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

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

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

Fig. 3: OF Fig. 3 Open Field

Fig. 4 EPM

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

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

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

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?!?