Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection
The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mech...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2008-08, Vol.33 (9), p.2237-2250 |
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| creator | Biber, Knut Pinto-Duarte, A Wittendorp, M C Dolga, A M Fernandes, C C Von Frijtag Drabbe Künzel, J Keijser, J N de Vries, R Ijzerman, A P Ribeiro, J A Eisel, U Sebastião, A M Boddeke, H W G M |
| description | The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A
1
receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A
1
receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling. |
| doi_str_mv | 10.1038/sj.npp.1301612 |
| format | Article |
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1
receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A
1
receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/sj.npp.1301612</identifier><identifier>PMID: 17987062</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adenosine ; Analysis of Variance ; Animals ; Autoradiography - methods ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; Cell Survival - drug effects ; Cells, Cultured ; Cerebral Cortex - cytology ; Cytokines ; Embryo, Mammalian ; Enzyme Inhibitors - pharmacology ; Excitatory Amino Acid Agents - pharmacology ; Excitatory Postsynaptic Potentials - drug effects ; Excitatory Postsynaptic Potentials - radiation effects ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Hippocampus - drug effects ; Hippocampus - physiology ; Hypoxia ; Interleukin-6 - deficiency ; Interleukin-6 - pharmacology ; Laboratories ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nervous system (semeiology, syndromes) ; Neurology ; Neurons - drug effects ; Neurosciences ; original-article ; Pentylenetetrazole - pharmacology ; Pharmacotherapy ; Physiology ; Polyclonal antibodies ; Psychiatry ; Radioligand Assay - methods ; Receptor, Adenosine A1 - genetics ; Receptor, Adenosine A1 - metabolism ; Seizures - chemically induced ; Seizures - drug therapy ; Seizures - genetics ; Synaptic Transmission - drug effects ; Time Factors ; Up-Regulation - drug effects</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2008-08, Vol.33 (9), p.2237-2250</ispartof><rights>American College of Neuropsychopharmacology 2008</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Aug 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.npp.1301612$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.npp.1301612$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20532377$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17987062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Biber, Knut</creatorcontrib><creatorcontrib>Pinto-Duarte, A</creatorcontrib><creatorcontrib>Wittendorp, M C</creatorcontrib><creatorcontrib>Dolga, A M</creatorcontrib><creatorcontrib>Fernandes, C C</creatorcontrib><creatorcontrib>Von Frijtag Drabbe Künzel, J</creatorcontrib><creatorcontrib>Keijser, J N</creatorcontrib><creatorcontrib>de Vries, R</creatorcontrib><creatorcontrib>Ijzerman, A P</creatorcontrib><creatorcontrib>Ribeiro, J A</creatorcontrib><creatorcontrib>Eisel, U</creatorcontrib><creatorcontrib>Sebastião, A M</creatorcontrib><creatorcontrib>Boddeke, H W G M</creatorcontrib><title>Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacol</addtitle><addtitle>Neuropsychopharmacology</addtitle><description>The immunological response in the brain is crucial to overcome neuropathological events. Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A
1
receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A
1
receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.</description><subject>Adenosine</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Autoradiography - methods</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - cytology</subject><subject>Cytokines</subject><subject>Embryo, Mammalian</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Excitatory Amino Acid Agents - pharmacology</subject><subject>Excitatory Postsynaptic Potentials - drug effects</subject><subject>Excitatory Postsynaptic Potentials - radiation effects</subject><subject>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - physiology</subject><subject>Hypoxia</subject><subject>Interleukin-6 - deficiency</subject><subject>Interleukin-6 - pharmacology</subject><subject>Laboratories</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Neurons - drug effects</subject><subject>Neurosciences</subject><subject>original-article</subject><subject>Pentylenetetrazole - pharmacology</subject><subject>Pharmacotherapy</subject><subject>Physiology</subject><subject>Polyclonal antibodies</subject><subject>Psychiatry</subject><subject>Radioligand Assay - methods</subject><subject>Receptor, Adenosine A1 - genetics</subject><subject>Receptor, Adenosine A1 - metabolism</subject><subject>Seizures - chemically induced</subject><subject>Seizures - drug therapy</subject><subject>Seizures - genetics</subject><subject>Synaptic Transmission - drug effects</subject><subject>Time Factors</subject><subject>Up-Regulation - drug effects</subject><issn>0893-133X</issn><issn>1740-634X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpFkc1LxDAQxYMouq5ePUoRPHY3k6RJ621Z_FhYFMSFvZU0TZfWblKT9uB_b0urngbe_OYNMw-hG8ALwDRe-mphmmYBFAMHcoJmIBgOOWX7UzTDcUJDoHR_gS69rzCGSPD4HF2ASGKBOZkhuzGtdrXuPksT8mDXOH3oatlqH7zqzlkj62CVa2N9aXSwguBdK9201vmHYHNs6lLJtrTGB4V148TR5oNBLwbS5KPWONtqNWhX6KyQtdfXU52j3dPjx_ol3L49b9arbdgQAiSkgHEecwDGEi3ymIgIEsx4lnDgiaCEM6pYIjLCiVKFghhLqqiUmCeYZIzO0d3o26_-6rRv08p2rr_Gp4REhMSMDdDtBHXZUedp48qjdN_p73t64H4CpFeyLpw0qvR_HMERJVSInluOnO9b5qDd_zbA6RBU6qu0DyqdgqI_lSWD-A</recordid><startdate>200808</startdate><enddate>200808</enddate><creator>Biber, Knut</creator><creator>Pinto-Duarte, A</creator><creator>Wittendorp, M C</creator><creator>Dolga, A M</creator><creator>Fernandes, C C</creator><creator>Von Frijtag Drabbe Künzel, J</creator><creator>Keijser, J N</creator><creator>de Vries, R</creator><creator>Ijzerman, A P</creator><creator>Ribeiro, J A</creator><creator>Eisel, U</creator><creator>Sebastião, A M</creator><creator>Boddeke, H W G M</creator><general>Springer International Publishing</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope></search><sort><creationdate>200808</creationdate><title>Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection</title><author>Biber, Knut ; Pinto-Duarte, A ; Wittendorp, M C ; Dolga, A M ; Fernandes, C C ; Von Frijtag Drabbe Künzel, J ; Keijser, J N ; de Vries, R ; Ijzerman, A P ; Ribeiro, J A ; Eisel, U ; Sebastião, A M ; Boddeke, H W G M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p2212-3100d8611449e7d827519046b96169732643c497b262ccfc180a3c3aa06902b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenosine</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Autoradiography - methods</topic><topic>Behavioral Sciences</topic><topic>Biological and medical sciences</topic><topic>Biological Psychology</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - cytology</topic><topic>Cytokines</topic><topic>Embryo, Mammalian</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Excitatory Amino Acid Agents - pharmacology</topic><topic>Excitatory Postsynaptic Potentials - drug effects</topic><topic>Excitatory Postsynaptic Potentials - radiation effects</topic><topic>Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. 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Some inflammatory mediators, such as the immunoregulatory cytokine interleukin-6 (IL-6) affect neuromodulation and may also play protective roles against various noxious conditions. However, the fundamental mechanisms underlying the long-term effects of IL-6 in the brain remain unclear. We now report that IL-6 increases the expression and function of the neuronal adenosine A
1
receptor, with relevant consequences to synaptic transmission and neuroprotection. IL-6-induced amplification of A
1
receptor function enhances the responses to readily released adenosine during hypoxia, enables neuronal rescue from glutamate-induced death, and protects animals from chemically induced convulsing seizures. Taken together, these results suggest that IL-6 minimizes the consequences of excitotoxic episodes on brain function through the enhancement of endogenous adenosinergic signaling.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>17987062</pmid><doi>10.1038/sj.npp.1301612</doi><tpages>14</tpages></addata></record> |
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| issn | 0893-133X 1740-634X |
| language | eng |
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| subjects | Adenosine Analysis of Variance Animals Autoradiography - methods Behavioral Sciences Biological and medical sciences Biological Psychology Cell Survival - drug effects Cells, Cultured Cerebral Cortex - cytology Cytokines Embryo, Mammalian Enzyme Inhibitors - pharmacology Excitatory Amino Acid Agents - pharmacology Excitatory Postsynaptic Potentials - drug effects Excitatory Postsynaptic Potentials - radiation effects Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Hippocampus - drug effects Hippocampus - physiology Hypoxia Interleukin-6 - deficiency Interleukin-6 - pharmacology Laboratories Male Medical sciences Medicine Medicine & Public Health Mice Mice, Inbred C57BL Mice, Knockout Nervous system (semeiology, syndromes) Neurology Neurons - drug effects Neurosciences original-article Pentylenetetrazole - pharmacology Pharmacotherapy Physiology Polyclonal antibodies Psychiatry Radioligand Assay - methods Receptor, Adenosine A1 - genetics Receptor, Adenosine A1 - metabolism Seizures - chemically induced Seizures - drug therapy Seizures - genetics Synaptic Transmission - drug effects Time Factors Up-Regulation - drug effects |
| title | Interleukin-6 Upregulates Neuronal Adenosine A1 Receptors: Implications for Neuromodulation and Neuroprotection |
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