TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ
Microglia (tissue-resident macrophages) represent the main cell type of the innate immune system in the CNS; however, the mechanisms that control the activation of microglia are widely unknown. We systematically explored microglial activation and functional microglia-neuron interactions in organotyp...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2016
|
| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2016, Jahrgang: 113, Heft: 1, Pages: 212-217 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.1513853113 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.1513853113 Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/113/1/212 
|
| Verfasserangaben: | Ismini E. Papageorgiou, Andrea Lewen, Lukas V. Galow, Tiziana Cesetti, Jörg Scheffel, Tommy Regen, Uwe-Karsten Hanisch, and Oliver Kann |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1702897370 | ||
| 003 | DE-627 | ||
| 005 | 20220818134615.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200630s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.1513853113 |2 doi | |
| 035 | |a (DE-627)1702897370 | ||
| 035 | |a (DE-599)KXP1702897370 | ||
| 035 | |a (OCoLC)1341341973 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Papageorgiou, Ismini E. |d 1982- |e VerfasserIn |0 (DE-588)1064119417 |0 (DE-627)812954823 |0 (DE-576)423646788 |4 aut | |
| 245 | 1 | 0 | |a TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ |c Ismini E. Papageorgiou, Andrea Lewen, Lukas V. Galow, Tiziana Cesetti, Jörg Scheffel, Tommy Regen, Uwe-Karsten Hanisch, and Oliver Kann |
| 246 | 3 | 3 | |a TLR 4-activated microglia require IFN-gamma to induce severe neuronal dysfunction and death in situ |
| 246 | 3 | 3 | |a TLR four-activated microglia require IFN-gamma to induce severe neuronal dysfunction and death in situ |
| 264 | 1 | |c 2016 | |
| 300 | |a 6 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Im Titel ist "gamma" als griechischer Buchstabe dargestellt | ||
| 500 | |a First published December 22, 2015 | ||
| 500 | |a Gesehen am 30.06.2020 | ||
| 520 | |a Microglia (tissue-resident macrophages) represent the main cell type of the innate immune system in the CNS; however, the mechanisms that control the activation of microglia are widely unknown. We systematically explored microglial activation and functional microglia-neuron interactions in organotypic hippocampal slice cultures, i.e., postnatal cortical tissue that lacks adaptive immunity. We applied electrophysiological recordings of local field potential and extracellular K+ concentration, immunohistochemistry, design-based stereology, morphometry, Sholl analysis, and biochemical analyses. We show that chronic activation with either bacterial lipopolysaccharide through Toll-like receptor 4 (TLR4) or leukocyte cytokine IFN-γ induces reactive phenotypes in microglia associated with morphological changes, population expansion, CD11b and CD68 up-regulation, and proinflammatory cytokine (IL-1β, TNF-α, IL-6) and nitric oxide (NO) release. Notably, these reactive phenotypes only moderately alter intrinsic neuronal excitability and gamma oscillations (30-100 Hz), which emerge from precise synaptic communication of glutamatergic pyramidal cells and fast-spiking, parvalbumin-positive GABAergic interneurons, in local hippocampal networks. Short-term synaptic plasticity and extracellular potassium homeostasis during neural excitation, also reflecting astrocyte function, are unaffected. In contrast, the coactivation of TLR4 and IFN-γ receptors results in neuronal dysfunction and death, caused mainly by enhanced microglial inducible nitric oxide synthase (iNOS) expression and NO release, because iNOS inhibition is neuroprotective. Thus, activation of TLR4 in microglia in situ requires concomitant IFN-γ receptor signaling from peripheral immune cells, such as T helper type 1 and natural killer cells, to unleash neurotoxicity and inflammation-induced neurodegeneration. Our findings provide crucial mechanistic insight into the complex process of microglia activation, with relevance to several neurologic and psychiatric disorders. | ||
| 650 | 4 | |a hippocampus | |
| 650 | 4 | |a microglia | |
| 650 | 4 | |a neuronal activity | |
| 650 | 4 | |a slice culture | |
| 650 | 4 | |a Toll-like receptor | |
| 700 | 1 | |a Lewen, Andrea |e VerfasserIn |0 (DE-588)1181730813 |0 (DE-627)166236427X |4 aut | |
| 700 | 1 | |a Galow, Lukas |d 1990- |e VerfasserIn |0 (DE-588)1129631702 |0 (DE-627)884264726 |0 (DE-576)486471527 |4 aut | |
| 700 | 1 | |a Cesetti, Tiziana |e VerfasserIn |0 (DE-588)115867323X |0 (DE-627)1020743360 |0 (DE-576)504286501 |4 aut | |
| 700 | 1 | |a Scheffel, Jörg |e VerfasserIn |4 aut | |
| 700 | 1 | |a Regen, Tommy |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hanisch, Uwe-Karsten |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kann, Oliver |d 1971- |e VerfasserIn |0 (DE-588)123125812 |0 (DE-627)70617223X |0 (DE-576)293567255 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |a National Academy of Sciences (Washington, DC) |t Proceedings of the National Academy of Sciences of the United States of America |d Washington, DC : National Acad. of Sciences, 1915 |g 113(2016), 1, Seite 212-217 |h Online-Ressource |w (DE-627)254235379 |w (DE-600)1461794-8 |w (DE-576)073260509 |x 1091-6490 |7 nnas |
| 773 | 1 | 8 | |g volume:113 |g year:2016 |g number:1 |g pages:212-217 |g extent:6 |a TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ |
| 856 | 4 | 0 | |u https://doi.org/10.1073/pnas.1513853113 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.pnas.org/content/113/1/212 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20200630 | ||
| 993 | |a Article | ||
| 994 | |a 2016 | ||
| 998 | |g 123125812 |a Kann, Oliver |m 123125812:Kann, Oliver |d 50000 |d 53200 |e 50000PK123125812 |e 53200PK123125812 |k 0/50000/ |k 1/50000/53200/ |p 8 |y j | ||
| 998 | |g 115867323X |a Cesetti, Tiziana |m 115867323X:Cesetti, Tiziana |d 50000 |d 53200 |e 50000PC115867323X |e 53200PC115867323X |k 0/50000/ |k 1/50000/53200/ |p 4 | ||
| 998 | |g 1129631702 |a Galow, Lukas |m 1129631702:Galow, Lukas |p 3 | ||
| 998 | |g 1181730813 |a Lewen, Andrea |m 1181730813:Lewen, Andrea |d 50000 |d 53200 |e 50000PL1181730813 |e 53200PL1181730813 |k 0/50000/ |k 1/50000/53200/ |p 2 | ||
| 999 | |a KXP-PPN1702897370 |e 3692302401 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"titleAlt":[{"title":"TLR 4-activated microglia require IFN-gamma to induce severe neuronal dysfunction and death in situ"},{"title":"TLR four-activated microglia require IFN-gamma to induce severe neuronal dysfunction and death in situ"}],"note":["Im Titel ist \"gamma\" als griechischer Buchstabe dargestellt","First published December 22, 2015","Gesehen am 30.06.2020"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"recId":"1702897370","language":["eng"],"title":[{"title":"TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ","title_sort":"TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ"}],"person":[{"given":"Ismini E.","family":"Papageorgiou","role":"aut","display":"Papageorgiou, Ismini E.","roleDisplay":"VerfasserIn"},{"family":"Lewen","given":"Andrea","display":"Lewen, Andrea","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","display":"Galow, Lukas","roleDisplay":"VerfasserIn","given":"Lukas","family":"Galow"},{"given":"Tiziana","family":"Cesetti","role":"aut","roleDisplay":"VerfasserIn","display":"Cesetti, Tiziana"},{"given":"Jörg","family":"Scheffel","role":"aut","display":"Scheffel, Jörg","roleDisplay":"VerfasserIn"},{"family":"Regen","given":"Tommy","display":"Regen, Tommy","roleDisplay":"VerfasserIn","role":"aut"},{"role":"aut","display":"Hanisch, Uwe-Karsten","roleDisplay":"VerfasserIn","given":"Uwe-Karsten","family":"Hanisch"},{"family":"Kann","given":"Oliver","roleDisplay":"VerfasserIn","display":"Kann, Oliver","role":"aut"}],"physDesc":[{"extent":"6 S."}],"relHost":[{"pubHistory":["1.1915 -"],"part":{"text":"113(2016), 1, Seite 212-217","volume":"113","extent":"6","year":"2016","pages":"212-217","issue":"1"},"titleAlt":[{"title":"PNAS online"},{"title":"PNAS"}],"note":["Gesehen am 09.03.2022"],"disp":"National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America","type":{"bibl":"periodical","media":"Online-Ressource"},"corporate":[{"role":"aut","roleDisplay":"VerfasserIn","display":"National Academy of Sciences"}],"language":["eng"],"recId":"254235379","title":[{"title_sort":"Proceedings of the National Academy of Sciences of the United States of America","title":"Proceedings of the National Academy of Sciences of the United States of America"}],"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"dateIssuedKey":"1915","publisher":"National Acad. of Sciences","dateIssuedDisp":"1915-","publisherPlace":"Washington, DC"}],"id":{"issn":["1091-6490"],"eki":["254235379"],"zdb":["1461794-8"]}}],"origin":[{"dateIssuedKey":"2016","dateIssuedDisp":"2016"}],"id":{"doi":["10.1073/pnas.1513853113"],"eki":["1702897370"]},"name":{"displayForm":["Ismini E. Papageorgiou, Andrea Lewen, Lukas V. Galow, Tiziana Cesetti, Jörg Scheffel, Tommy Regen, Uwe-Karsten Hanisch, and Oliver Kann"]}} | ||
| SRT | |a PAPAGEORGITLR4ACTIVA2016 | ||