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Article: Neurons reduce glial responses to lipopolysaccharide (LPS) and prevent injury of microglial cells from over-activation by LPS

TitleNeurons reduce glial responses to lipopolysaccharide (LPS) and prevent injury of microglial cells from over-activation by LPS
Authors
Issue Date2001
PublisherBlackwell Publishing Ltd.
Citation
Journal Of Neurochemistry, 2001, v. 76 n. 4, p. 1042-1049 How to Cite?
AbstractThe microenvironment of the CNS has been considered to tonically inhibit glial activities. It has been shown that glia become activated where neuronal death occurs in the aging brain. We have previously demonstrated that neurons tonically inhibit glial activities including their responses to the bacterial endotoxin lipopolysaccharide (LPS). It is not clear whether activation of glia, especially microglia in the aging brain, is the consequence of disinhibition due to neuronal death. This study was designed to determine if glia regain their responsiveness to LPS once the neurons have died in aged cultures. When cultured alone, glia from postnatal day one rat mesencephalons stimulated with LPS (0.1-1000 ng/mL) produced both nitric oxide (NO) and tumor necrosis factor α (TNFα), yielding a sigmoid and a bell-shaped curve, respectively. When neuron-containing cultures were prepared from embryonic day 14/15 mesencephalons, the shape of the dose-response curve for NO was monotonic and the bell-shaped curve for TNFα production was shifted to the right. After 1 month of culture under conditions where neurons die, the production curves for NO and TNFα in LPS-stimulated glia shifted back to the left compared to mixed neuron-glia cultures. Immunostaining of rat microglia for the marker CR3 (the receptor for complement component C3) demonstrated that high concentrations of LPS (1 μg/mL) reduced the number of microglia in mixed-glial cultures. In contrast, reduction of CR3 immunostaining was not observed in LPS-stimulated mixed neuron-glia cultures. Taken together, the results demonstrate that disinhibition of the glial response to LPS occurs after neurons die in aged cultures. Once neurons have died, the responsiveness of glia to LPS is restored. Neurons prevented injury to microglia by reducing their responsiveness to LPS. This study broadens our understanding of the ways in which the CNS microenvironment affects cerebral inflammation.
Persistent Identifierhttp://hdl.handle.net/10722/67964
ISSN
2015 Impact Factor: 3.842
2015 SCImago Journal Rankings: 2.021
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChang, RCCen_HK
dc.contributor.authorChen, Wen_HK
dc.contributor.authorHudson, Pen_HK
dc.contributor.authorWilson, Ben_HK
dc.contributor.authorHan, DSKen_HK
dc.contributor.authorHong, JSen_HK
dc.date.accessioned2010-09-06T05:59:52Z-
dc.date.available2010-09-06T05:59:52Z-
dc.date.issued2001en_HK
dc.identifier.citationJournal Of Neurochemistry, 2001, v. 76 n. 4, p. 1042-1049en_HK
dc.identifier.issn0022-3042en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67964-
dc.description.abstractThe microenvironment of the CNS has been considered to tonically inhibit glial activities. It has been shown that glia become activated where neuronal death occurs in the aging brain. We have previously demonstrated that neurons tonically inhibit glial activities including their responses to the bacterial endotoxin lipopolysaccharide (LPS). It is not clear whether activation of glia, especially microglia in the aging brain, is the consequence of disinhibition due to neuronal death. This study was designed to determine if glia regain their responsiveness to LPS once the neurons have died in aged cultures. When cultured alone, glia from postnatal day one rat mesencephalons stimulated with LPS (0.1-1000 ng/mL) produced both nitric oxide (NO) and tumor necrosis factor α (TNFα), yielding a sigmoid and a bell-shaped curve, respectively. When neuron-containing cultures were prepared from embryonic day 14/15 mesencephalons, the shape of the dose-response curve for NO was monotonic and the bell-shaped curve for TNFα production was shifted to the right. After 1 month of culture under conditions where neurons die, the production curves for NO and TNFα in LPS-stimulated glia shifted back to the left compared to mixed neuron-glia cultures. Immunostaining of rat microglia for the marker CR3 (the receptor for complement component C3) demonstrated that high concentrations of LPS (1 μg/mL) reduced the number of microglia in mixed-glial cultures. In contrast, reduction of CR3 immunostaining was not observed in LPS-stimulated mixed neuron-glia cultures. Taken together, the results demonstrate that disinhibition of the glial response to LPS occurs after neurons die in aged cultures. Once neurons have died, the responsiveness of glia to LPS is restored. Neurons prevented injury to microglia by reducing their responsiveness to LPS. This study broadens our understanding of the ways in which the CNS microenvironment affects cerebral inflammation.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Ltd.en_HK
dc.relation.ispartofJournal of Neurochemistryen_HK
dc.rightsJournal of Neurochemistry. Copyright © Blackwell Publishing Ltd.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAntigens, CDen_HK
dc.subject.meshAntigens, CD147en_HK
dc.subject.meshAntigens, Neoplasmen_HK
dc.subject.meshAntigens, Surfaceen_HK
dc.subject.meshAvian Proteinsen_HK
dc.subject.meshBlood Proteinsen_HK
dc.subject.meshCell Counten_HK
dc.subject.meshCell Survival - drug effectsen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCoculture Techniquesen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshLipopolysaccharides - pharmacologyen_HK
dc.subject.meshMembrane Glycoproteins - metabolismen_HK
dc.subject.meshMesencephalon - cytology - drug effects - embryology - metabolismen_HK
dc.subject.meshMicroglia - cytology - drug effects - metabolismen_HK
dc.subject.meshNeuroglia - cytology - drug effects - metabolismen_HK
dc.subject.meshNeurons - cytology - drug effects - metabolismen_HK
dc.subject.meshNitric Oxide - biosynthesisen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Inbred F344en_HK
dc.subject.meshTime Factorsen_HK
dc.subject.meshTumor Necrosis Factor-alpha - biosynthesisen_HK
dc.titleNeurons reduce glial responses to lipopolysaccharide (LPS) and prevent injury of microglial cells from over-activation by LPSen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3042&volume=76&spage=1042&epage=1049&date=2001&atitle=Neurons+reduce+glial+responses+to+lipopolysaccharide+(LPS)+and+prevent+injury+of+microglial+cells+from+over-activation+by+LPSen_HK
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_HK
dc.identifier.authorityChang, RCC=rp00470en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1046/j.1471-4159.2001.00111.xen_HK
dc.identifier.pmid11181823-
dc.identifier.scopuseid_2-s2.0-0035116418en_HK
dc.identifier.hkuros64021en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035116418&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume76en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1042en_HK
dc.identifier.epage1049en_HK
dc.identifier.isiWOS:000167049800010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChang, RCC=7403713410en_HK
dc.identifier.scopusauthoridChen, W=55168776300en_HK
dc.identifier.scopusauthoridHudson, P=35566903000en_HK
dc.identifier.scopusauthoridWilson, B=35243580200en_HK
dc.identifier.scopusauthoridHan, DSK=36985828100en_HK
dc.identifier.scopusauthoridHong, JS=7404117981en_HK

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