دورية أكاديمية
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 |
|---|---|
| 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 (UCA), Université Clermont Auvergne (UCA), 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 - CNRS Chimie (INC-CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Faculty of Chemistry Krakow, 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) |
| المصدر: | ISSN: 0301-0082 ; Progress in Neurobiology ; https://uca.hal.science/hal-02906397Test ; Progress in Neurobiology, 2020, 193, pp.101846. ⟨10.1016/j.pneurobio.2020.101846⟩. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2020 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | Neuropathic pain, Cognitive deficit, 5-HT6 receptor, Constitutive activity, mTOR, Inverse agonist, MESH: Animals, MESH: Behavior Animal/drug effects, MESH: Male, MESH: Mice, Inbred C57BL, Transgenic, MESH: Neuralgia/complications, MESH: Neuralgia/drug therapy, MESH: Neuralgia/metabolism, MESH: Nociception/drug effects, MESH: Rats, Sprague-Dawley, MESH: Receptors, Serotonin/drug effects, MESH: Cognitive Dysfunction/drug therapy, Serotonin/metabolism, MESH: Serotonin Agents/administration & dosage, MESH: Serotonin Agents/pharmacology, MESH: TOR Serine-Threonine Kinases/drug effects, MESH: TOR Serine-Threonine Kinases/metabolism, MESH: Cognitive Dysfunction/etiology, MESH: Cognitive Dysfunction/metabolism, 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32512114; hal-02906397; https://uca.hal.science/hal-02906397Test; https://uca.hal.science/hal-02906397/documentTest; https://uca.hal.science/hal-02906397/file/Martin-Prog-Neurobiol.pdfTest; PUBMED: 32512114 |
| DOI: | 10.1016/j.pneurobio.2020.101846 |
| الإتاحة: | https://doi.org/10.1016/j.pneurobio.2020.101846Test https://uca.hal.science/hal-02906397Test https://uca.hal.science/hal-02906397/documentTest https://uca.hal.science/hal-02906397/file/Martin-Prog-Neurobiol.pdfTest |
| حقوق: | http://creativecommons.org/licenses/byTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.3D2DAFD8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.pneurobio.2020.101846 |
|---|