Seite - 105 - in Advances in Neuroimmunology

BrainSci. 2017,7, 14 particular setofgeneregulation features (namedpertubagens)was likely tobeconnectedwith the genes listed in theLINCSreport. Positivereadings in theConsensusKnockdownConnections in the report indicate thatknockdownof thegenes listed in theLINCSreportwouldmatch thegenechanges input into theQueryApp,andthus thegeneswithhighscores representpotential targetgenes for the experimental treatment. 3.Results 3.1. ExpressionProfile of Inflammasome-RelatedGenesFollowinganLPSChallenge,withandwithout MorphineTolerance Alterations ingeneexpressionweremeasured in rats challengedwithLPS,withandwithout morphine tolerance, using a PCR array containing 84 genes related to inflammasome activation and function. NLRP12 expression was significantly decreased in response to LPS in both the morphine-tolerant (morphine-tolerant+LPS)andcontrol (placebo-control+LPS)rats, comparedtothe ratsgivensaline(morphine-tolerant+salineandplacebo-control+saline) (Figure1,Table1).However, thedecreasewasgreater in theplacebo-control rats (−7.3 fold;p<0.01) than in themorphine-tolerant rats (−4.5 fold;p<0.05). Pla ce bo -co ntr ol+ Sa lin e Pla ce bo -co ntr ol+ LP S Mo rp hin e-t ole ran t+S ali ne Mo rp hin e-t ole ran t+L PS -8 -6 -4 -2 0 2 Naip2 Nlrp12 Nlrp5 Nlrc4 Nlrp1a Nlrp3 Nlrp6 Nlrx1 ** * Figure1. Inflammasome-relatedgeneexpression in the ratbrain in response to lipopolysaccharide (LPS),withandwithoutmorphine tolerance. Theexpressionof the inflammasome-relatedNOD-like receptor (NLR)genes (Naip2,Nlrp12,Nlrp5,Nlrc4,Nlrp1a,Nlrp3,Nlrp6,AndNlrx1) in thebrainsof ratsgivenan i.p. injectionofeither250μg/kgLPSorsaline,withandwithoutmorphine tolerance (n=3–5 ratspergroup),wasdeterminedusingaPCRarray. Datawerecalculatedusing theΔΔCT method, relative to thecontrolgroup(placebo-control+saline),andarerepresentedasa foldchange. * p < 0.05, ** p < 0.01. Naip2: NLR family, apoptosis inhibitory protein 6; Nlrp12: NLR Family PyrinDomainContaining12;Nlrp5: NLRFamilyPyrinDomainContaining5;Nlrc4: NLRFamily CARDDomainContaining4;Nlrp1a:NLRfamily,pyrindomaincontaining1A;Nlrp3:NLRFamily PyrinDomainContaining3;Nlrp6: NLRFamilyPyrinDomainContaining6;Nlrpx1: NLRfamily memberX1. 105