000912541 001__ 912541 000912541 005__ 20230123110758.0 000912541 0247_ $$2doi$$a10.3389/fphar.2022.1038285 000912541 0247_ $$2Handle$$a2128/33073 000912541 0247_ $$2pmid$$a36408236 000912541 0247_ $$2WOS$$aWOS:000885546500001 000912541 037__ $$aFZJ-2022-05714 000912541 082__ $$a610 000912541 1001_ $$0P:(DE-HGF)0$$aKlein, Ines$$b0 000912541 245__ $$aGlia from the central and peripheral nervous system are differentially affected by paclitaxel chemotherapy via modulating their neuroinflammatory and neuroregenerative properties 000912541 260__ $$aLausanne$$bFrontiers Media$$c2022 000912541 3367_ $$2DRIVER$$aarticle 000912541 3367_ $$2DataCite$$aOutput Types/Journal article 000912541 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1670931424_2542 000912541 3367_ $$2BibTeX$$aARTICLE 000912541 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000912541 3367_ $$00$$2EndNote$$aJournal Article 000912541 520__ $$aGlia are critical players in defining synaptic contacts and maintaining neuronal homeostasis. Both astrocytes as glia of the central nervous system (CNS), as well as satellite glial cells (SGC) as glia of the peripheral nervous system (PNS), intimately interact with microglia, especially under pathological conditions when glia regulate degenerative as well as regenerative processes. The chemotherapeutic agent paclitaxel evokes peripheral neuropathy and cognitive deficits; however, the mechanisms underlying these diverse clinical side effects are unclear. We aimed to elucidate the direct effects of paclitaxel on the function of astrocytes, microglia, and SGCs, and their glia-glia and neuronal-glia interactions. After intravenous application, paclitaxel was present in the dorsal root ganglia of the PNS and the CNS of rodents. In vitro, SGC enhanced the expression of pro-inflammatory factors and reduced the expression of neurotrophic factor NT-3 upon exposure to paclitaxel, resulting in predominantly neurotoxic effects. Likewise, paclitaxel induced a switch towards a pro-inflammatory phenotype in microglia, exerting neurotoxicity. In contrast, astrocytes expressed neuroprotective markers and increasingly expressed S100A10 after paclitaxel exposure. Astrocytes, and to a lesser extent SGCs, had regulatory effects on microglia independent of paclitaxel exposure. Data suggest that paclitaxel differentially modulates glia cells regarding their (neuro-) inflammatory and (neuro-) regenerative properties and also affects their interaction. By elucidating those processes, our data contribute to the understanding of the mechanistic pathways of paclitaxel-induced side effects in CNS and PNS.Keywords: paclitaxel, chemotherapy-related neurotoxicity, neuroinflammation, astrocytes, microglia, satellite glia cells, neural stem cells, BDNF (brain derived neurotrophic factor) 000912541 536__ $$0G:(DE-HGF)POF4-5251$$a5251 - Multilevel Brain Organization and Variability (POF4-525)$$cPOF4-525$$fPOF IV$$x0 000912541 588__ $$aDataset connected to CrossRef, Journals: juser.fz-juelich.de 000912541 7001_ $$0P:(DE-HGF)0$$aBoenert, Janne$$b1 000912541 7001_ $$0P:(DE-HGF)0$$aLange, Felix$$b2 000912541 7001_ $$0P:(DE-HGF)0$$aChristensen, Britt$$b3 000912541 7001_ $$0P:(DE-HGF)0$$aWassermann, Meike K.$$b4 000912541 7001_ $$0P:(DE-HGF)0$$aWiesen, Martin H. J.$$b5 000912541 7001_ $$0P:(DE-HGF)0$$aOlschewski, Daniel Navin$$b6 000912541 7001_ $$0P:(DE-HGF)0$$aRabenstein, Monika$$b7 000912541 7001_ $$0P:(DE-HGF)0$$aMüller, Carsten$$b8 000912541 7001_ $$0P:(DE-HGF)0$$aLehmann, Helmar C.$$b9 000912541 7001_ $$0P:(DE-Juel1)131720$$aFink, Gereon Rudolf$$b10$$ufzj 000912541 7001_ $$0P:(DE-HGF)0$$aSchroeter, Michael$$b11 000912541 7001_ $$0P:(DE-HGF)0$$aRueger, Maria Adele$$b12 000912541 7001_ $$0P:(DE-HGF)0$$aVay, Sabine Ulrike$$b13$$eCorresponding author 000912541 773__ $$0PERI:(DE-600)2587355-6$$a10.3389/fphar.2022.1038285$$gVol. 13, p. 1038285$$p1038285$$tFrontiers in pharmacology$$v13$$x1663-9812$$y2022 000912541 8564_ $$uhttps://juser.fz-juelich.de/record/912541/files/PDF.pdf$$yOpenAccess 000912541 909CO $$ooai:juser.fz-juelich.de:912541$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000912541 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)131720$$aForschungszentrum Jülich$$b10$$kFZJ 000912541 9131_ $$0G:(DE-HGF)POF4-525$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5251$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vDecoding Brain Organization and Dysfunction$$x0 000912541 9141_ $$y2022 000912541 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-04 000912541 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-02-04 000912541 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000912541 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000912541 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2021-02-04 000912541 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-04 000912541 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2021-02-04 000912541 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFRONT PHARMACOL : 2021$$d2022-11-09 000912541 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-09 000912541 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-09 000912541 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2021-05-11T14:28:21Z 000912541 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2021-05-11T14:28:21Z 000912541 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Blind peer review$$d2021-05-11T14:28:21Z 000912541 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-09 000912541 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-09 000912541 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-09 000912541 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2022-11-09 000912541 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bFRONT PHARMACOL : 2021$$d2022-11-09 000912541 920__ $$lyes 000912541 9201_ $$0I:(DE-Juel1)INM-3-20090406$$kINM-3$$lKognitive Neurowissenschaften$$x0 000912541 980__ $$ajournal 000912541 980__ $$aVDB 000912541 980__ $$aUNRESTRICTED 000912541 980__ $$aI:(DE-Juel1)INM-3-20090406 000912541 9801_ $$aFullTexts