Page - 1 - in Advances in Neuroimmunology

brain sciences Review Impactof IncreasedAstrocyteExpressionofIL-6, CCL2orCXCL10inTransgenicMiceonHippocampal SynapticFunction DonnaGruol MolecularandCellularNeuroscienceDepartment,TheScrippsResearchInstitute,La Jolla,CA92037,USA; gruol@scripps.edu;Tel.:+1-858-784-7060;Fax:+1-858-784-7393 AcademicEditor: BalapalS.Basavarajappa Received: 17May2016;Accepted: 13 June2016;Published: 17 June2016 Abstract:AnimportantaspectofCNSdiseaseandinjury is theelevatedexpressionofneuroimmune factors. These factors are thought to contribute toprocesses ranging fromrecoveryandrepair to pathology. Thecomplexityof theCNSandthemultitudeofneuroimmunefactors thatareexpressed in theCNSduringdisease and injury is a challenge to anunderstandingof the consequences of theelevatedexpressionrelative toCNSfunction. Oneapproach toaddress this issue is theuseof transgenicmice thatexpresselevated levelsofaspecificneuroimmunefactor in theCNSbyacell type thatnormallyproduces it. Thisapproachcanprovidebasic informationabout theactionsof specificneuroimmunefactorsandcancontribute toanunderstandingofmorecomplexconditions whenmultipleneuroimmunefactorsareexpressed. Thisreviewsummarizesstudiesusingtransgenic mice thatexpresselevated levelsof IL-6,CCL2orCXCL10throughincreasedastrocyteexpression. Thestudies focusontheeffectsof theseneuroimmunefactorsonsynaptic functionat theSchaffer collateral toCA1pyramidalneuronsynapseof thehippocampus,abrainregionthatplaysakeyrole incognitive function. Keywords: pyramidal neurons; Schaffer collaterals; LTP; neuroimmune; alcohol; field potential recordings; cytokine; chemokine 1. Introduction Several linesofevidencehaveconfirmedtheexistenceofaneuroimmunesystemintheCNS,anda role forneuroimmunecommunication inCNShomeostasis, function,andpathology.Glial cells, andin particular astrocytes andmicroglia, are themain cellular components of the CNSneuroimmune system. Glial cells initiate neuroimmune communication primarily through the production of small protein signaling factorswith distinct structure and function. These neuroimmune factors includemembersof thecytokinesuperfamilysuchasproinflammatorycytokinesandchemokines. Typically,proinflammatorycytokinesandchemokinesarepresentat lowlevels in thenormalCNS, while elevate levels are associatedwithCNSdisease and injury. For example, elevated levels of proinflammatorycytokinesand/orchemokines in theCNSare typicalhallmarksofCNSinflammatory and neurodegenerative diseases such asHIV infection [1], Alzheimer’s disease [2], epilepsy [3], multiplesclerosis [4], alcoholismandfetalalcohol spectrumdisorders [5–7], andpsychiatricdisorders (e.g., autismspectrumdisorders, schizophrenia,depression) [8–10]. Theelevatedlevelsare thought contribute topathologicalprocessesoccurring in theseconditions,althoughprotectiveactionscould alsoplayarole. Elevatedlevelsof theseneuroimmunefactorsalsooccur innormalaging,andmay playarole incognitivedecline thatcanoccurwithnormalaging[11,12]. BrainSci. 2016,6, 19 1 www.mdpi.com/journal/brainsci