Seite - 10 - in Advances in Neuroimmunology

BrainSci. 2016,6, 19 Takentogether, theseresultsshowthatmechanismsthat induceLTPandPTParesensitivetoacute exposure to IL-6orCXCL10. Thus, the lackofgenotypicdifferences inLTPandPTPbetweenthe IL-6 tgandnon-tghippocampusandtheCXCL10-tgandnon-tghippocampusmayreflectneuroadaptive changes inmechanismsthat induceLTPandPTP.Theseneuroadaptivechangesproducedanapparent normalizationof function. Effectsofacute, exogenousapplicationofCCL2onPTPandLTPhavenot beenreported. 6. ProteinLevels inHippocampus IL-6,CCL2,andCXCL10signal transductionpathwayscanleadtodownstreameffectsongene expression and, consequently, changes in the levels of important cellular and synaptic proteins. Changes inprotein levelscouldalsooccur throughother regulatorymechanisms. Suchneuroadaptive changescould impactsynaptic function.Westernblotstudieswerecarriedout to identifypotential changes inprotein levels in thehippocampusfromIL-6 tgandCCL2-tgmice.CXCL10-tgmicehave notexamined.Relatively fewchanges inprotein levelswereobservedinthehippocampusfromthe IL-6 tgandCCL2-tgmicecomparedtohippocampusfromtheir respectivenon-tgmice,asshownin Table3. Theseresultsareconsistentwith therelative lackofneuropathological changesobservedin thehippocampusfromtheIL-6 tgandCCL2-tgmiceat theagesstudied.However, somedifferences wereobservedthatcouldaffect synaptic function. Table3.Genotypicdifferencesonprotein levels inhippocampus. Measurement IL-6 tgvs.Non-tg CCL2-tgvs. Non-tg CCL2-tgSJL vs.Non-tg Age(months) 1–2 3–5 1–3 3–5 3–4 7–9 Housekeepingproteins -β-actin noΔ noΔ noΔ noΔ noΔ noΔ Astrocyteproteins -GFAP Ò Ò noΔ noΔ noΔ Ò -Glutaminesynthetase noΔ noΔ noΔ noΔ nd nd Microglialprotein -CD11b nd noΔ noΔ nd Ò noΔ Neuronalproteins -Enolase noΔ noΔ noΔ noΔ noΔ noΔ -GAD65/67 noΔ Ó noΔ noΔ noΔ noΔ Synapticproteins -Synapsin1 noΔ noΔ noΔ Ò noΔ noΔ -VGLUT1 nd noΔ noΔ nd nd nd -GluA1 noΔ noΔ noΔ noΔ noΔ noΔ -GluN1 noΔ noΔ Ò Ò noΔ noΔ Signal transduction -STAT3 Ò Ò noΔ nd nd nd -p42/44MAPK noΔ noΔ noΔ noΔ nd nd Reference [58,60] [58,67] [61] Ó=decrease,Ò=increase,noΔ=nodifference,nd=notdetermined. Comparedtothehippocampusfromnon-tgmice, thehippocampusfromIL-6 tgmiceshowed elevatedlevelsofGFAPandSTAT3, thesignal transductionmoleculethat is involvedinIL-6regulation ofGFAPgeneexpression[59,60]. The levelofphosphorylated(i.e., activated)STAT3wasalsoelevated in thehippocampusfromIL-6 tgmice [59,60].Anotherastrocyticprotein,glutamatesynthetase,which is involved inglutamatecycling,an importantaspectofexcitatorysynaptic transmission[80],wasnot altered in thehippocampusfromthe IL-6 tgmice [60], suggesting that the increased levelsofGFAPdo notreflectageneralactionof IL-6onastrocyticprotein levels. The increased levelsofactivatedSTAT3 10