title: Anger Emotional Stress Influences VEGF/VEGFR2 and Its Induced PI3K/AKT/mTOR Signaling Pathway.
abstract: Objective. We discuss the influence of anger emotional stress upon VEGF/VEGFR2 and its induced PI3K/AKT/mTOR signal pathway. Methods. We created a rat model of induced anger (anger-out and anger-in) emotional response using social isolation and resident-intruder paradigms and assessed changes in hippocampus' VEGF content, neuroplasticity, and the PI3K/AKT/mTOR signaling pathway. Results. The resident-intruder method successfully generated anger-out and anger-in models that differed significantly in composite aggression score, aggression incubation, open field behavior, sucrose preference, and weight gain. Anger emotional stress decreased synaptic connections and VEGFR2 expression. Anger emotional stress led to abnormal expression of VEGF/VEGFR2 mRNA and protein and disorderly expression of key factors in the PI3K/AKT/mTOR signal pathway. Fluoxetine administration ameliorated behavioral abnormalities and damage to hippocampal neurons caused by anger emotional stress, as well as abnormal expression of some proteins in VEGF/VEGFR2 and its induced PI3K/AKT/mTOR signal pathway. Conclusion. This research provides a detailed classification of anger emotion and verifies its influence upon VEGF and the VEGF-induced signaling pathway, thus providing circumstantial evidence of mechanisms by which anger emotion damages neurogenesis. As VEGFR2 can promote neurogenesis and vasculogenesis in the hippocampus and frontal lobe, these results suggest that anger emotional stress can result in decreased neurogenesis.
authors.affiliation: College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Experiment Center, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.affiliation: Technical Office of Pharmacology, Shandong Institute for Food and Drug Control, Jinan 250351, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wei
authors.affiliation: College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Preclinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Qiao
authors.affiliation: School of Preclinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.
authors.forename: Jibiao
authors.initials: J
authors.lastname: Wu
mesh_terms: D000786:Anger / Q000502:physiology*; D000818:Animals; D004291:Dominance-Subordination; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D012934:Social Isolation; D013315:Stress, Psychological / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C546845:mTOR protein, rat; C000602029:Kdr protein, rat