title: Antidepressant-like effects of alarin produced by activation of TrkB receptor signaling pathways in chronic stress mice.
abstract: Alarin is a newly identified member of the galanin family of neuropeptides. Until now, research on alarin is limited compared with other members of the galanin family. Unearthing the new biological effects of alarin and its unidentified receptor(s) interests us. We previously showed that alarin has an effect on depression-like behaviors, although the underlying mechanisms are not fully clarified. The present study verified the antidepressant-like effects of alarin using the unpredictable chronic mild stresses (UCMS) paradigm, and explored the mechanism that underlies antidepressant-like effects of alarin in mice. Previous research has shown that TrkB receptor-mediated ERK and AKT signaling pathways participate in depression pathophysiology. Therefore, we aimed to explore whether alarin improved depression-like behaviors by increasing activity of ERK and AKT pathways mediated by TrkB. Results showed that alarin significantly reduced immobility time in the forced swim test and latency to feed in the novelty suppressed feeding test. In addition, decreased p-ERK/ERK and p-AKT/AKT levels in the prefrontal cortex, hippocampus, olfactory bulb, and hypothalamus induced by UCMS were reversed by intracerebroventricular injection of alarin. Results suggested that alarin increased p-ERK/ERK and p-AKT/AKT levels by acting on the TrkB receptor. To verify this hypothesis, mice were pretreated with the TrkB inhibitor K252a (or 0.1% dimethyl sulfoxide, intraperitoneally, 3 days), followed by intracerebroventricular injection of alarin. This resulted in an absence of antidepressant-like effects, as well as no activation of ERK and AKT signaling pathways. Results demonstrate that alarin may exert antidepressant-like effects by targeting TrkB receptor-mediated ERK and AKT signal systems, which could help to identify the alarin receptor.
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China; Department of Pharmacy, The People's Hospital of Xinyi, Xuzhou 221004, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Fuzhi
authors.initials: F
authors.lastname: Zhuang
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Ma
authors.affiliation: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Department of Pharmacology, Xuzhou Medical College, Xuzhou 221004, China. Electronic address: gushling@aliyun.com.
authors.forename: Shuling
authors.initials: S
authors.lastname: Gu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002227:Carbazoles / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044089:Galanin-Like Peptide / Q000494:pharmacology*; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000928:Antidepressive Agents; D002227:Carbazoles; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D044089:Galanin-Like Peptide; D026121:Indole Alkaloids; C581934:alarin; C049985:staurosporine aglycone; D020813:Receptor, trkB; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: AKT; Alarin; Depression; Extracellular signal-regulated kinase; cAMP-response element binding protein