title: FGF2 alleviates PTSD symptoms in rats by restoring GLAST function in astrocytes via the JAK/STAT pathway.
abstract: In our previous study, we demonstrated that fibroblast growth factor 2 (FGF2) administration alleviated posttraumatic stress disorder (PTSD) symptoms via an "astrocyte-related" mechanism. We further investigated the changes in the astrocytic glutamate transporters GLAST and GLT-1 and in JAK/STAT3 signaling (which is involved in astrocyte activation and GLAST/GLT-1 function) in single prolonged stress (SPS) model rats. High-performance liquid chromatography (HPLC), Western blot and immunohistochemistry analyses revealed a significant SPS-induced increase in the concentration of glutamate in the cerebrospinal fluid and decrease in GLAST/GLT-1 expression and JAK/STAT3 signaling. Treatment with FGF2 significantly alleviated GLAST/GLT-1 dysfunction, JAK/STAT3 signaling inhibition, and the behavioral abnormalities. The administration of the JAK/STAT pathway inhibitor AG490 blocked the effects of FGF2 on PTSD symptoms, astrocyte activation, and GLAST, but not GLT-1, expression in vivo and in vitro. Our findings suggest that astrocytic JAK/STAT signaling is associated with SPS-induced GLAST dysfunction and that FGF2 protects against PTSD symptoms by restoring astrocytic glutamate uptake via the JAK/STAT signaling pathway.
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, PR China; Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Dayun
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Psychosomatics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Gaohua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Bao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: huaizhouqin@163.com.
authors.forename: Huaizhou
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Neurobiology and Collaborative Innovation Center for Brain Science, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: shengxi@fmmu.edu.cn.
authors.forename: Shengxi
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D005239:Fear / Q000187:drug effects / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D027341:Excitatory Amino Acid Transporter 1; D011619:Psychotropic Drugs; D050796:STAT3 Transcription Factor; C493392:Slc1a3 protein, rat; C494088:Stat3 protein, rat; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid; D053612:Janus Kinases
keywords: Astrocyte; FGF2; GLAST; PTSD; STAT3