Presentation

Confirmed speakers

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• Rita Bardoni , University of Modena and Reggio Emilia - IT

  

  Rita Bardoni

  University of Modena and Reggio Emilia

  Address:  Via Campi, 287 41125 Modena, Italy

   Email: rita.bardoni@unimore.it

  Rita Bardoni is an Associate Professor of Physiology at the University of Modena and Reggio Emilia. Her research focuses on the cellular and synaptic mechanisms underlying somatosensory transmission in the spinal cord dorsal horn. Using primarily electrophysiological approaches in in vitro spinal cord preparations, Dr. Bardoni has characterized the functional properties of identified dorsal horn neuronal populations and examined the role of specific synaptic receptors in the modulation of pain and itch signalling. More recently, her work has concentrated on the impact of serotonergic receptor activation on dorsal horn circuit activity, with particular emphasis on 5-HT1 and 5-HT7 receptors.

  5-HT7 receptor–mediated modulation of identified neuronal circuits in the superficial dorsal horn of the spinal cord

  5-HT7 receptors are abundantly expressed in the dorsal horn of the spinal cord, in both neuronal and glial populations. Their expression is predominantly associated with inhibitory GABAergic and glycinergic interneurons. Consistent with this distribution, behavioral studies indicate that spinal 5-HT7 receptors exert a primarily antinociceptive effect in both inflammatory and neuropathic pain models. Using an in vitro mouse spinal cord slice preparation, we showed that activation of 5-HT7 receptors by the selective agonist LP-211 modulates inhibitory synaptic transmission in laminae I–II of the dorsal horn, key regions for nociceptive processing. Specifically, LP-211 increased GABA and glycine release and enhanced the excitability of tonic-firing neurons, which are largely inhibitory interneurons. Optogenetic experiments further demonstrated that 5-HT7 receptor activation potentiates both spontaneous and light-evoked inhibitory synaptic transmission. This potentiation was mainly observed in excitatory interneurons, where inhibitory inputs were predominantly glycinergic. Consistently, preliminary data obtained with the 5-HT7 biased agonist serodolin revealed an increase in spontaneous inhibitory synaptic currents in excitatory interneurons.
  Overall, our results show that activation of 5-HT7 receptors strengthens inhibitory control over dorsal horn nociceptive interneurons, providing mechanistic support for the antinociceptive role of these receptors at the spinal level.

• Monika Bijata, Nencki Institute of Experimental Biology PAS - PL

  

  Monika Bijata

  Nencki Institute of Experimental Biology PAS

  Address:  Pasteur 3, 02-093 Warsaw - Poland

   Email: m.bijata@nencki.edu.pl

  Dr hab. Monika Bijata is a neuroscientist at the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw. Her research focuses on molecular and structural mechanisms of synaptic plasticity in neuropsychiatric disorders. She investigates how serotonin signaling, particularly via the 5-HT7 receptor, influences brain function under stress. Through a combination of behavioral, biochemical, imaging, and electrophysiological methods, she identified a novel signaling pathway linking 5-HT7 receptor activation with matrix metalloproteinase-9 (MMP-9) activity in the hippocampus. This pathway plays a key role in dendritic spine remodeling and the emergence of depressive-like behaviors, offering new insight into antidepressant mechanisms and potential therapeutic targets.

  5-HT7 receptor as a regulator of synaptic plasticity and molecular driver of depressive-like behaviors   

  Serotonergic signaling plays a fundamental role in regulating synaptic plasticity and emotional behavior. Our work synthesizes molecular and behavioral evidence identifying the 5-HT7 receptor (5-HT7R) as a critical modulator of hippocampal plasticity and a driver of depressive-like behaviors. We show that activation of 5-HT7R induces changes in synaptic structure. Acute and chronic 5-HT7R activation produce distinct synaptic and behavioral effects, with sustained receptor stimulation promoting maladaptive plasticity associated with depressive-like phenotypes in animal models. At the molecular level, these effects are mediated by a downstream signaling cascade involving matrix metalloproteinase-9 (MMP-9), which translates 5-HT7R activity into structural remodeling of dendritic spines and changes in synaptic efficacy. Importantly, the functional outcome of 5-HT7R signaling is further shaped by post-translational regulation, including receptor palmitoylation, which modulates constitutive receptor activity and downstream signaling and is disrupted under chronic stress conditions. It is associated with increased hippocampal MMP-9 activity, a finding mirrored in post mortem brain samples from individuals with depression. Together, these data position the 5-HT7R as a central molecular switch integrating serotonergic signaling, stress-dependent regulatory mechanisms, and synaptic remodeling underlying mood-related behaviors.

• Sylvie Claeysen , Institute of Functional Genomics (IGF) / INSERM, CNRS, Montpellier University - FR

  

  Sylvie Claeysen

  Institute of Functional Genomics (IGF) / INSERM, CNRS, University of Montpellier 

  Address:  141 rue de la Cardonille 34094 Montpellier cedex 5

   Email: sylvie.claeysen@igf.cnrs.fr

  Sylvie Claeysen is an Inserm researcher based at the Institute of Functional Genomics in Montpellier. She specialises in neuropharmacology, serotonin receptors and neurodegenerative diseases. Working with a network of clinicians, chemists and biotechnology companies, she proposes innovative strategies for treating Alzheimer's disease (multi-target drugs, biomarkers). A member of the Scientific Council of France Alzheimer (2015-2023) and of Inserm's Microbiota programme (2016-2025), she is currently a partner in the PREANALYTICS project of the national programme ‘Food Systems, Microbiomes and Health’ and co-leader of the MICMALZ clinical study. In this context, she is exploring the potential of gut microbiota modulation as a new therapeutic and preventive approach to Alzheimer's disease.

  Serotonin and the gut-brain axis  

  The gut microbiota plays a key role in human health and is capable of affecting brain function via the gut-brain axis. Serotonin plays a crucial role in this axis, acting as a signalling molecule that links gastrointestinal function with emotional and cognitive processes. Around 90% of the body’s serotonin is produced in the gut, where it regulates motility, secretion and sensory signalling. This peripheral serotonin interacts with the enteric nervous system and communicates with the central nervous system via neural pathways, particularly the vagus nerve, as well as through immune and endocrine routes. Disorders such as irritable bowel syndrome, anxiety, and depression are associated with alterations in serotonin signalling, highlighting its dual influence on gut and brain health. Understanding the integrative role of serotonin offers insight into novel therapeutic approaches that target gut-brain communication.

• Pascale Crépieux, Physiology of Reproduction and Behaviour (PRC) / Centre INRAE Val de Loire, CNRS, University of Tours, IFCE - FR

  

  Pascale Crépieux

  Physiology of Reproduction and Behaviour (PRC) / Centre INRAE Val de Loire, CNRS, University of Tours, IFCE

  Address:  Centre INRAE Val de Loire, 37380 Nouzilly, France

   Email: pascale.crepieux@inrae.fr

  Dr Pascale Crépieux is a CNRS research director at the Laboratory of Physiology of Reproduction and Behaviors in Nouzilly, France. She obtained her PhD in Molecular Oncology at the Pasteur Institute, France, then spent 3 years at McGill University, Canada, as a post-doc. Her research has revealed a developmental regulation of signalling processes during gonadal post-natal development, and have highlighted the importance of translational regulations in the trophic role of FSH in these cells. She is now exploring new approaches based on intracellular VHH, to interfere with the FSHR-mediated signalling and clarify the relationships between the FSHR structure and its activity. 

  Targeting FSHR and LHR with intracellular antibodies for structure-activity studies  

  Intracellular variable fragments of camelid heavy chain antibodies (intra-VHHs or nanobodies) have been successfully used as chaperones to resolve the 3D structure of active G protein-coupled receptors (GPCRs) bound to transducing proteins. They also provide insights into the relationships between receptor conformational states and signaling activity. So far, this property has been mainly examined for GPCRs binding peptide ligands. Using a next-generation sequencing approach after phage display selection with FSHR or its intracellular domains, we isolated and characterized several intra-VHHs, some of which also recognize LHCGR. Both receptors target gonadal cells and have key roles in orchestrating reproduction in Mammals. In my talk, I will present the functional impact of these intra-VHHs on FSHR and LHR signaling and trafficking and explain why these intra-VHHs may be useful to complement the structure/activity studies performed so far on gonadotropin receptors.

• Marcello Leopoldo, University of Bari Aldo Moro - IT

  

  Marcello Leopoldo

  University of Bari Aldo Moro 

  Address:  Dipartimento di Farmacia – Scienze del Farmaco, via Orabona 4, 70125 Bari - Italy

   Email: marcello.leopoldo@uniba.it

  Marcello Leopoldo is a full professor of Medicinal Chemistry at the University of Bari Aldo Moro (Italy). He has been studying the structure-activity relationships of small molecules targeting various G Protein-Coupled Receptors (GPCRs), including dopamine, serotonin, bombesin, and formyl peptide receptors, to identify drug-like selective agonists or antagonists as pharmacological tools, fluorescent probes, and positron emission tomography radioligands. He has authored more than 150 articles. One of the most relevant outcomes of his research is the brain-penetrant selective serotonin 5-HT7 receptor agonist LP-211, which indicated that 5-HT7 receptor activation may have therapeutic effects in neurodevelopmental diseases, such as Fragile X syndrome, Rett syndrome, and Angelman syndrome.

  Identification of the First-in-Class Photo-Activatable 5-HT7 Receptor Agonist

  The serotonin 5-HT7 receptor (5-HT7R) is a G protein-coupled receptor (GPCR) within the 5-HT receptor family, widely distributed across both peripheral tissues and the central nervous system (CNS). In the CNS, 5-HT₇R is expressed in limbic areas, the putamen, the raphe, the caudate nuclei, and cortical regions. This receptor plays a pivotal role in various physiological and pathophysiological processes, such as thermoregulation, circadian rhythm regulation, sleep, learning and memory, cognitive function, and stress response. Moreover, substantial evidence implicates 5-HT7R in mood disorders, including anxiety and depression. Investigating the specific roles of 5-HT7R in these complex processes poses significant challenges due to the intricate nature of CNS mechanisms. To this end, a photopharmacological approach might be of support. We will present the chemical design of a caged 5-HT7R agonist. Following the caging strategy, three photoprotective groups were attached to the basic nitrogen of two 5-HT7R ligands, resulting in reduced binding affinity. The new light-sensitive molecules release the agonist under suitable light conditions. The biological properties of the molecules released upon illumination have been studied in in vitro and ex vivo models, confirming that these tools can be used to study the role of 5-HT7R in a temporally controlled manner.

• Kara Margolis, New York University - USA

  

  Kara Margolis

  New York University

  Address:  433 First Avenue; NY, NY 10010 - USA

   Email: km5994@nyu.edu

  Kara Margolis is a Professor of Pediatrics and Cell biology at the NYU Grossman School of Medicine and a Professor of Molecular Pathobiology at the NYU College of Dentistry where she is also the Director for the NYU Pain Research Center. Dr. Margolis is a pediatric gastroenterologist and physician-scientist with clinical and scientific expertise in disorders that affect the gut and the brain, including abdominal pain-related disorders of gut brain interactions (DGBIs). In the laboratory, Dr. Margolis leads clinical, translational and basic science research programs whose themes center around the discovery of novel mediators that connect abdominal pain-linked disorders to mental health conditions like anxiety and depression.

  The role of serotonergic signaling in abdominal pain and mood dysfunction   

  Mood disorders and disorders of gut brain (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Though serotonergic drugs are often prescribed for both conditions, they are often unsuccessful and/or cause adverse effects.

  In this talk, Dr. Margolis will cover the patient presentations of these comorbid conditions, the physiology of gut serotonin in the context of mood and visceral pain and how we her laboratory has segued between mouse and human studies to develop a novel therapeutic concept for treating abdominal pain and mood disorders

• Evgeni Ponimaskin, Hannover Medical School - DE

  

  Evgeni Ponimaskin

  Dept. of Cellular Neurophysiology, Institute of Neurophysiology, Hannover Medical School 

  Address:  Carl-Neuberg-Str. 1, 30627 Hannover, Germany

   Email: Ponimaskin.Evgeni@mh-hannover.de

  Prof. Dr. Evgeni Ponimaskin is Professor of Cellular Neurophysiology at Hannover Medical School, Germany. He studied biochemistry at the University of Oldenburg and received his PhD from the Free University Berlin. After postdoctoral training in Berlin and Göttingen, he became group leader at the DFG Research Center “Molecular Physiology of the Brain” in Göttingen and obtained his habilitation in physiology. Since 2008 he heads the Department of Cellular Neurophysiology in Hannover. His research focuses on molecular mechanisms of neurodegeneration, particularly serotonin receptor signalling, tau pathology, and therapeutic strategies for tauopathies using cellular and animal models.

  Serotonin 5-HT7 Receptor as a Therapeutic Target in Tauopathies: From Mechanism to Intervention  

  Aggregation of the microtubule-associated protein Tau drives tauopathies, including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Although the serotonergic system has re-emerged as a therapeutic target in neurodegeneration, the contribution of specific serotonin receptors to pathological Tau aggregation remained unclear.
  We identified a causal link between the constitutive activity of the serotonin GPCR 5-HT7 (5-HT7R) and pathological Tau hyperphosphorylation as well as neurofibrillary tangle formation in primary neurons and cortical neurons in vivo. Mechanistically, 5-HT7R physically interacts with the Tau kinase CDK5, inducing its G protein-independent activation. We defined the structural determinants of the 5-HT7R–CDK5 interaction and mapped their binding interface.
  Structural and functional screening identified clinically approved drugs with strong inverse agonism at 5-HT7R, with amisulpride emerging as a lead compound. Using biochemical, pharmacological, imaging, and behavioral analyses in primary mouse neurons, human iPSC-derived neurons carrying an FTD-associated Tau mutation, and two tauopathy mouse models, we demonstrated that amisulpride reduces Tau hyperphosphorylation, tangle formation, apoptosis, and memory deficits. We have also initiated treatment of three FTD patients under individual therapeutic use. Moreover, we optimized amisulpride structure to enhance 5-HT7R selectivity and reduce side effects.  
  These findings establish inverse agonism at 5-HT7R as a novel therapeutic strategy for tauopathies.

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