Seite - 9 - in Advances in Neuroimmunology

BrainSci. 2016,6, 19 mechanisms involved in transmitter release. LTP, the delayed, persistent, stable increase in the magnitudeof the fEPSPisprimarilyaresultofactivity-inducedchanges inpost-synapticmechanisms. Results fromstudiesof long-termsynapticplasticityareshowninTable1. IntheIL-6tgline, therewasnogenotypicdifferenceinLTPbetweenIL-6andnon-tghippocampus frombothyoung(1–2monthsofage)andadult (3–6monthsofage)mice. PTPwasreduced in the hippocampusfromyoung(1–2monthsofage) IL-6 tgmicecomparedto thehippocampusfromnon-tg mice, indicatingchanges inpresynaptic function,agenotypiceffect thatwasnotobservedfor IL-6and non-tghippocampusfromadultmice (3–6monthsofage) [60]. InboththeCCL2-tgandCXCL10-tg lines,nogenotypiceffectonPTPorLTPwasobservedbetweenthehippocampusfromtransgenicvs. non-tgmice [67,68]. PTPwasenhanced in thehippocampus fromtheCCL2-tgSJLmicecompared with thehippocampusfromthenon-tgmice,but therewasnogenotypicdifference inLTP. 5.3. Effect ofAcuteApplicationofNeuroimmuneFactorsonSynapticFunction Inadditiontostudiesof thehippocampusfromtransgenicmice, studiesontheeffectsofacute, exogenousappliedIL-6orCXCL10onsynaptic transmissionandplasticityat theSchaffercollateral toCA1pyramidalsynapsehavebeencarriedout inhippocampalslices fromratormice. Theeffect of acute exposure is of interest because it presumably reflects to some degree the actions of the endogenouscytokineorchemokineduringthe initial stagesofelevatedexpression in the transgenic mice. Resultsaresummarized inTable2. TherewasnosignificanteffectofexogenouslyappliedIL-6 on the fEPSPorPSof rat hippocampal slices. Therewas alsono significant effect of exogenously appliedCXCL10onthefEPSPinhippocampalslices fromtheCXCL10tgandnon-tgmice [68]. The effectofacute, exogenousappliedCCL2onsynaptic transmissionwasstudied in therathippocampal slicesusingwholecellvoltageclamptechniques.CCL2enhancedtheexcitatorypostsynapticcurrents elicitedbystimulationof theSchaffercollaterals, aneffect showntoresult fromactionsofCCL2on presynapticmechanisms[75,76]. Althoughacute, exogenous applicationof IL-6orCXCL10hadnoeffect onbaseline synaptic transmission, IL-6significantly reducedPTPandLTPinrathippocampal slices [77,78]. Exogenous applicationofCXCL-10also significantly reducedbothPTPandLTPhippocampal slices fromthe non-tgmice, but onlyLTP inhippocampal slices fromCXCL10-tgmice [68]. The lack of effect of CXCL-10onPTPintheCXCL10-tghippocampus, suggestneuroadaptivechanges in theCXCL10-tg mice thatprevent theactionsofacuteCXCL-10. Table2.Effectsofexogenousapplicationofneuroimmunefactoronsynaptic functioninhippocampus. Measurement NeuroimmuneFactor IL-6 CCL2 CXCL10non-tg CXCL10tg species rat rat rat mouse mouse Age(months)orweight (gm) 2–3months 200–250gm 0.5–1month 5–6months 5–6months Concentration 1,5,50ng/mL 50–2000U/mL 2.3nM 10ng/mL 10ng/mL Synaptic transmission -fEPSPorEPSC nd noΔ Ò noΔ nd -Populationspike noΔ nd nd nd nd Short-termsynapticplasticity -fEPSP(PPF) noΔ nd nd Ò noΔ -Populationspike (PPR) nd nd nd nd nd Long-termsynapticplasticity -PTP Ó Ó nd Ó noΔ -LTP Ó Ó nd Ó Ó Reference [79] [78] [75] [68] Ó=decrease,Ò=increase,noΔ=nodifference,nd=notdetermined. EPSC=excitatorypostsynapticcurrent. 9