Gastrodinamelioratesdepression-likebehaviorsandup-regulates

proliferationofhippocampal-derivedneuralstemcellsinrats:Involvementofitsanti-inflammatoryaction

Abstract

Gastrodin(GAS),anactiveconstituentoftheChineseherbalmedicinetianma,hasantidepressant-likeactivityinanimalsbutnospecificmolecularmechanismshavebeenidentified.Inthepresentstudy,chronicunpredictablestress(CUS)wasusedtoestablisharatdepressionmodel;

Thesucrosepreferencetest,forcedswimtestandMorriswatermazetestwereusedtoassessdepression-likebehaviors(anhedonia,behavioraldespair,motorretardation,andpoorspatialmemory),andtheproliferationofhippocampalstemcellswastestedbyBrdUimmunohistochemistry.

ThestressandinflammatoryresponseswereassayedbymeasuringIL-RA,NF-κB,andp-iκBexpressionbyWesternblotandIL-1βproductionbyELISA.DirectandindirecteffectsofGASonNSCviablecellnumberwereexaminedinvitrobyWST-1andBrdUassays.ItwasfoundthatGAS(mg/kgdaily)reversedalltesteddepression-likebehaviorsinCUSmodelratsandup-regulatedNSCsproliferationinthehippocampus.Enhancedexpressionofp-iκB,NFκB,andIL-1βbyCUSwasalsoreversedbyGAS.

Moreover,invitroexperimentsrevealedthatGASalonedidnotincreasetheviabilityofNSCsbutprotectedthemfromIL-1β-induceddamage.TheseresultssupporttheantidepressantandneuroprotectiveeffectsofGAS,andGASmayreducedepression-likebehaviorsbyprotectinghippocampalNSCsagainsttheproinflammatorycytokineIL-1β.

1.Background

AccordingtotheWorldHealthOrganization,depressionwill

rankasthesecondmost