mTOR activation by constitutively active serotonin6 receptors as new paradigm in neuropathic pain and its treatment
| العنوان: | mTOR activation by constitutively active serotonin6 receptors as new paradigm in neuropathic pain and its treatment |
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| المؤلفون: | Martin, Pierre-Yves, Doly, Stéphane, Hamieh, Al Mahdy, Chapuy, Eric, Canale, Vittorio, Drop, Marcin, Chaumont-Dubel, Séverine, Bantreil, Xavier, Lamaty, Frédéric, Bojarski, Andrzej, Zajdel, Pawel, Eschalier, Alain, Marin, Philippe, COURTEIX, Christine |
| المساهمون: | Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), ANR-17-CE16-0010,Sero6Dev,Réseau de signalisation associé au récepteur 5-HT6 et développement neuronal(2017), ANR-17-CE16-0013,StopSero6TOR,La signalisation mTOR induite par le récepteur 5-HT6 comme cible thérapeutique pour prévenir l'apparition des déficits cognitifs dans la schizophrénie(2017), ANR-19-CE18-0018,SERO6Pain,Les voies de signalisation du récepteur 5-HT6: de nouvelles cibles pour le traitement de la douleur neuropathique?(2019), COURTEIX, Christine, Réseau de signalisation associé au récepteur 5-HT6 et développement neuronal - - Sero6Dev2017 - ANR-17-CE16-0010 - AAPG2017 - VALID, La signalisation mTOR induite par le récepteur 5-HT6 comme cible thérapeutique pour prévenir l'apparition des déficits cognitifs dans la schizophrénie - - StopSero6TOR2017 - ANR-17-CE16-0013 - AAPG2017 - VALID, Les voies de signalisation du récepteur 5-HT6: de nouvelles cibles pour le traitement de la douleur neuropathique? - - SERO6Pain2019 - ANR-19-CE18-0018 - AAPG2019 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Université Clermont Auvergne (UCA) |
| المصدر: | Progress in Neurobiology Progress in Neurobiology, Elsevier, 2020, 193, pp.101846. ⟨10.1016/j.pneurobio.2020.101846⟩ Progress in Neurobiology, 2020, 193, pp.101846. ⟨10.1016/j.pneurobio.2020.101846⟩ |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | MESH: Cognitive Dysfunction/drug therapy, Male, Nociception, MESH: Neuralgia/drug therapy, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Hyperalgesia/drug therapy, MESH: Rats, Sprague-Dawley, MESH: Nociception/drug effects, Neuropathic pain, MESH: Neuralgia/complications, Rats, Sprague-Dawley, Serotonin Agents, MESH: Animals, MESH: Receptors, Serotonin/drug effects, Neuropathic pain Cognitive deficit 5-HT6 receptor Constitutive activity mTOR Inverse agonist, Behavior, Animal, TOR Serine-Threonine Kinases, MESH: Hyperalgesia/metabolism, MESH: Cognitive Dysfunction/metabolism, [SDV] Life Sciences [q-bio], MESH: Serotonin Agents/pharmacology, Hyperalgesia, MESH: HEK293 Cells, mTOR, MESH: Neuralgia/metabolism, Inverse agonist, MESH: Serotonin Agents/administration & dosage, MESH: Behavior Animal/drug effects, MESH: Rats, MESH: Mice, Transgenic, MESH: Cognitive Dysfunction/etiology, Mice, Transgenic, MESH: TOR Serine-Threonine Kinases/metabolism, Constitutive activity, MESH: Mice, Inbred C57BL, Animals, Humans, Cognitive Dysfunction, MESH: Humans, Cognitive deficit, MESH: Receptors, Serotonin/metabolism, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: TOR Serine-Threonine Kinases/drug effects, MESH: Male, Rats, Mice, Inbred C57BL, Disease Models, Animal, HEK293 Cells, 5-HT6 receptor, Receptors, Serotonin, Neuralgia, MESH: Disease Models, Animal |
| الوصف: | International audience; Chronic neuropathic pain is a highly disabling syndrome that is poorly controlled by currently available analgesics. Here, we show that painful symptoms and associated cognitive deficits induced by spinal nerve ligation in the rat are prevented by the administration of serotonin 5-HT6 receptor inverse agonists or by the mTOR inhibitor rapamycin. In contrast, they are not alleviated by the administration of 5-HT6 receptor neutral antagonists. Likewise, activation of mTOR by constitutively active 5-HT6 receptors mediates allodynia in oxaliplatin-induced peripheral neuropathy in rats but not mechanical nociception in healthy rats. Furthermore, both painful and co-morbid cognitive symptoms in neuropathic rats are strongly reduced by intrathecal delivery of a cell-penetrating peptide that disrupts 5-HT6 receptor/mTOR physical interaction. Collectively, these findings demonstrate a deleterious influence of non-physiological mTOR activation by constitutively active spinal 5-HT6 receptors upon painful and cognitive symptoms in neuropathic pains of different etiologies. They suggest that targeting the constitutive activity of 5-HT6 receptors with inverse agonists or disrupting the 5-HT6 receptor/mTOR interaction might be valuable strategies for the alleviation of neuropathic pain and cognitive co-morbidities. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0301-0082 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::8aef17b38cdcef4604d7c319d906c1cbTest https://hal.uca.fr/hal-02906397/documentTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....8aef17b38cdcef4604d7c319d906c1cb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03010082 |
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