FGF2 blocks PTSD symptoms via an astrocyte-based mechanism

Behav Brain Res. 2013 Nov 1:256:472-80. doi: 10.1016/j.bbr.2013.08.048. Epub 2013 Sep 5.

Abstract

Although posttraumatic stress disorder (PTSD) is characterized by traumatic memories or experiences and increased arousal, which can be partly alleviated by antidepressants, the underlying cellular mechanisms are not fully understood. As emerging studies have focused on the critical role of astrocytes in pathological mood disorders, we hypothesized that several 'astrocyte-related' mechanisms underlying PTSD exist. In the present study, using the single prolonged stress (SPS) model, we investigated the effects of intraperitoneal FGF2 on SPS-induced PTSD behavior response as well as the astrocytic activation after FGF2 administration in SPS rats. Behavioral data showed that intraperitoneal FGF2 inhibited SPS-induced hyperarousal and anxiety behavior; however, immunohistochemistry showed that SPS-induced astrocytic inhibition was activated by intraperitoneal FGF2. Quantitative western blotting showed that intraperitoneal FGF2 up-regulated glial fibrillary acidic protein (GFAP), but not NeuN, expression in the hippocampus. We suggest that intraperitoneal FGF2 could block the SPS-induced fear response and anxiety behavior in PTSD via astrocyte-based but not neuron-based mechanisms.

Keywords: Astrocyte; EPM; Elevated plus maze; FGF2; Fear response; GFAP; OF; Open field; PBS; PTSD; SPS; elevated plus maze; fibroblast growth factor 2; glial fibrillary acidic protein; open field; phosphate buffered saline; posttraumatic stress disorders; single prolonged stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism
  • Arousal / drug effects
  • Astrocytes / drug effects*
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Fear / drug effects
  • Fear / physiology
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblast Growth Factor 2 / therapeutic use
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Nerve Tissue Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Stress, Psychological / drug therapy*
  • Up-Regulation / drug effects

Substances

  • Antigens, Nuclear
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat
  • Fibroblast Growth Factor 2