Seite - 12 - in Advances in Neuroimmunology

BrainSci. 2016,6, 19 Table4.Effectsofalcoholonsynaptic function inhippocampus. Measurement 60mMAlcoholvs.Baseline Non-tg IL-6 tg Non-tg CCL2-tg Synaptic transmission -fEPSP Ó Ò Ó Ó -PS Ó Ò Ó Ó P-Psynapticplasticity -fEPSP(PPF) noΔ noΔ noΔ noΔ -PS (PPR) Ò noΔ Ò noΔ Long-termsynapticplasticity -PTP Ó noΔ Ó noΔ -LTP Ó noΔ Ó noΔ Reference [70] [67] Ó=decrease,Ò=increase,noΔ=nodifference. Adifference in response toalcoholwasalsoobserved inbehavioral studiesof alcoholactions. In one study of alcoholwithdrawal hyperexcitability, IL-6 tg andCCL2-tgmice and their non-tg littermateswere exposed to an acute, highdose of alcohol (4 gm/kg, i.p.), which initially causes sedation,butduringthephaseofdecliningbloodalcohol levels,CNShyperexcitability isproduced. Thehyperexcitabilitywasmeasuredbyhandling inducedconvulsions (HIC) [83,84]. The IL-6 tgmice showedsignificantlyhigherHICscores thantheirnon-tgcontrols, indicatinggreaterhyperexcitability, whereas CCL2-tg and their non-tgmice showed similarHIC scores [70]. In behavioral tests for contextual fearconditioning, therewerenosignificantdifferencesbetweentheCCL2-tgandnon-tg mice under baseline conditions. Acute alcohol (1 gm/kg, i.p.) significantly impaired the non-tg micebutnot theCCL2-tgmice in thisbehavioral test [67]. In contrast, in the rotorod test,which is consideredprimarilyacerebellarmediatedbehavior,CCL2-tgandnon-tgmiceshownodifference in recovery fromtheeffectsof acutealcohol (2gm/kg, i.p.) [67]. Asimilar resultwasobtained for theeffectsof acutealcohol (2gm/kg, i.p.) on IL-6 tgandnon-tgmice in the rotarod test (recovery time=176.2˘9.3minfornon-tgand171.2˘9.0minfor IL-6 tg). Covert changeswere also revealed in other studies of the IL-6 tgmice. Systemic exposure (i.p. injection) toa lowdoseofkainateorNMDAinducedprominentseizuresandlethality in IL-6-tg mice but not in thenon-tgmice,which required ahigherdose toproduce such effects [69]. Also, basalplasmacorticosterone levelswerenormal in IL-6-tgmicebut,after restraint stress,abnormally increased levelswereobservedin the IL-6 tgmicecomparedtonon-tgmice [85]. Thus, inadditionto thedetectedneuroadaptivechanges inbaseline functionsandbehavior, covertneuroadaptivechanges areproducedbythechronicexposure to IL-6andCCL2andcanberevealedwithincertaincontexts. Suchneuroadaptivechangescouldplayanimportant role inpathophysiological conditions. 9.Conclusions Although a large literature has demonstrated elevated CNS expression of cytokines and chemokines in CNSdisease and injury, a relatively small number of studies have examined the consequencesof theelevatedexpressionat thesynaptic level. The transgenicapproachprovides tools for suchstudies. Transgenicmodels that targetastrocyteproductionofneuroimmunefactorshave enabledstudies thatprovideabasicunderstandingof thesynaptic consequenceofpersistentelevated expressionof a specificneuroimmune factorby thisCNScell type. This information can facilitate identificationofpotential contributionsof theneuroimmunefactor toamorecomplexconditionwhen multipleneuroimmunefactorsareexpressed. This informationmayalsobeuseful for identificationof theactions/roleof specificneuroimmunefactors inCNSphysiology. Theastrocyte targeted transgenic models complement traditional approaches involving knock out (KO)models. In theKOmodel, all cell types are affected and, therefore, the KOmodels providemore global information about 12