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DTSTART;TZID=Europe/Paris:20250905T143000
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CREATED:20250218T103042Z
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UID:180664-1757082600-1757082600@www.bordeaux-neurocampus.fr
SUMMARY:Thesis defense - Thibault Dhellemmes
DESCRIPTION:Venue: Centre Broca Nouvelle-Aquitaine \nThesis defended in french \n \n\nThibault Dhellemmes\n \nTeam: Purinergic mediated neuroinflammation and brain disorders\nThesis directed by Marc Landry\nIMN \nTitle\nStudy of morpho-functionnal plasticity of Relaxin-3/RXFP3 peptidergic system\, in chronic pain condition \nAbstract\nAt least 25% of the global population is currently affected by chronic pain\, with 85% of these individuals presenting with psychiatric comorbidities. Despite this high prevalence\, available treatments remain poorly adapted. Pain is a multidimensional process integrated across various regions of the pain matrix (somatosensory cortex\, anterior cingulate cortex [ACC]\, amygdala). Under pathological pain conditions\, these neural circuits undergo anatomical and functional rearrangements that are largely controlled by neuropeptides. \nOur hypothesis is that the relaxin-3 (RLN3)/RXFP3 peptidergic system plays a key role in pain neural networks and could represent an innovative target for the treatment of pathological pain. To test this hypothesis\, we used models of persistent inflammatory pain (CFA model) and chronic neuropathic pain (Cuff model)\, induced in transgenic mice (RLN3-Cre\, RLN3-Cre::SOM-Flp) as well as in wild-type mice.\nFrom an anatomical perspective\, a tissue-clearing approach enabled visualization of all RLN3 projections originating from the nucleus incertus (NI). We developed an automated method for quantitative 3D analysis of fluorescence signals\, which revealed\, under CFA conditions\, an increase in RXFP3 mRNA expression in somatostatin (SOM)-positive interneurons\, and a decrease in interactions between RLN3 fibers in the ACC and SOM interneurons. This RLN3–SOM interaction\, in proximity to PV (parvalbumin) neurons\, was further confirmed using a correlative microscopy approach (CLEM). \nFunctionally\, we demonstrated an antinociceptive effect resulting from both acute and chronic activation of the RXFP3 receptor in the ACC and the amygdala\, along with its impact on associated psychiatric comorbidities. We also confirmed this antinociceptive effect following optogenetic activation of the relaxin-3 system at the level of the NI or its projections in the ACC. The specificity of this effect was further confirmed by using a selective RXFP3 antagonist in the ACC. Patch-clamp experiments also showed a decrease in the activity of RLN3 neurons in the NI under CFA and Cuff conditions. \nThese findings highlight RLN3 as a promising target for the development of effective therapeutic solutions addressing both the affective and sensory components of pain. \nKey words\nChronic pain\, Neuropeptide\, Relaxin-3\, GPCR\, Neuroanatomy\, Anterior cingulate cortex\, Nociception \nJury\nDr. Myriam ANTRI\, MCU / Université Clermont Auvergne\, Rapportrice\nDr. Pierre VEINANTE\, PU / Université de Strasbourg\, Rapporteur\nDr. Aude PANATIER\, DR / Université de Bordeaux\, Examinatrice\nDr. Cyril RIVAT\, PU / Université de Montpellier\, Examinateur\nDr. Matilde CORDERO-ERAUSQUIN\, DR / Université de Strasbourg\, Examinatrice \n
URL:https://www.bordeaux-neurocampus.fr/en/event/soutenance-de-these-thibault-dhellemmes/
CATEGORIES:IMN,Thesis
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