title: Gastrodin ameliorates depression-like behaviors and up-regulates proliferation of hippocampal-derived neural stem cells in rats: involvement of its anti-inflammatory action.
abstract: Gastrodin (GAS), an active constituent of the Chinese herbal medicine tianma, has antidepressant-like activity in animals but no specific molecular mechanisms have been identified. In the present study, chronic unpredictable stress (CUS) was used to establish a rat depression model; The sucrose preference test, forced swim test and Morris water maze test were used to assess depression-like behaviors (anhedonia, behavioral despair, motor retardation, and poor spatial memory), and the proliferation of hippocampal stem cells was tested by BrdU immunohistochemistry. The stress and inflammatory responses were assayed by measuring IL-RA, NF-κB, and p-iκB expression by Western blot and IL-1β production by ELISA. Direct and indirect effects of GAS on NSC viable cell number were examined in vitro by WST-1 and BrdU assays. It was found that GAS (200 mg/kg daily) reversed all tested depression-like behaviors in CUS model rats and up-regulated NSCs proliferation in the hippocampus. Enhanced expression of p-iκB, NF-κB, and IL-1β by CUS was also reversed by GAS. Moreover, in vitro experiments revealed that GAS alone did not increase the viability of NSCs but protected them from IL-1β-induced damage. These results support the antidepressant and neuroprotective effects of GAS, and GAS may reduce depression-like behaviors by protecting hippocampal NSCs against the proinflammatory cytokine IL-1β.
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Huaning
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ruiguo
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Nie
authors.affiliation: School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Electronic address: zhangzj@hku.hk.
authors.forename: Zhangjin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: pengzhengwu1446@163.com.
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: tanqingr@fmmu.edu.cn.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Tan
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001592:Benzyl Alcohols / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005518:Food Preferences / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D058953:Neural Stem Cells / Q000187:drug effects*; D051381:Rats; D013315:Stress, Psychological / Q000150:complications; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D001592:Benzyl Alcohols; D005960:Glucosides; D013395:Sucrose; C045345:gastrodin
keywords: Chronic unpredictable stress; Depression; Gastrodin; Hippocampal stem cell; IL-1β; Inflammation