NeuroDegen

Epigenetics and dynamics of memory systems

Leaders: Dr. Anne-Laurence BOUTILLIER et Pr. Jean-Christophe CASSEL
Research unit: Laboratory of Cognitive and Adaptative Neuroscience (LNCA) UMR 7364

The team's research focuses on the functional dynamics of memory consolidation and on the molecular and cellular mechanisms - particularly epigenetic mechanisms - responsible for memory deficits in neurodegenerative diseases (Alzheimer's disease and related disorders, Lewy body and fronto-temporal dementias, Huntington's disease). We are looking for epigenetic/transcriptomic signatures associated with the pathology (integrated analyses by high-throughput sequencing: RNA-seq, ChIP-seq, CUT & Tag-seq, ATAC-seq, 4C-seq...), in the different brain regions involved and in a cell-specific manner (neurons, astrocytes, micoglia, oligodendrocytes...). sorted by FACS/FANS or magnetic beads) from transgenic animal models (THY-Tau22, Thy1-SNCA, FUS∆NLS, HD R6/1, HD KI-Q140,...). We are studying how these signatures are modified by learning, and/or certain genetic (e.g. EpoE3/4) or environmental (e.g. radio frequency) risk factors, as well as by environmental enrichment (social, physical, novelty). The neurodegenerative diseases we study are currently incurable and many clinical tests have recently failed. Our research in neuro-epigenetics deciphers fundamental mechanisms associated with the diseases and could provide new therapeutic leads. The studies conducted in our team include characterisation from the molecular to the behavioural scale.

ENGRAM

Leaders: Dr. Chantal MATHIS et Dr. Lucas LECOURTIER
Research unit: Laboratory of Cognitive and Adaptative Neuroscience (LNCA) UMR 7364

ENGRAM aims to identify the neural networks involved in the elaboration and reactivation of a memory engram during spatial memory, recognition or fear conditioning tasks. The fate of these networks is also studied during ageing and in pathological conditions (mainly models of Alzheimer's disease and depression). Early biomarkers of Alzheimer's disease: we are evaluating the earliest markers of cognitive decline and alterations in neuronal networks in parallel with the emergence of neuropathological signs characteristic of Alzheimer's disease in mouse models. Lateral habenula, memory, stress: through behavioural, electrophysiological and pharmacogenetic approaches, we are determining the role of neural networks involving the lateral habenula in spatial memory, and emotional processes (fear conditioning, stress response). Depression: we are involved in collaborative research projects exploring the validity of therapeutic strategies such as deep brain stimulation and ketamine administration. Housing conditions and cognitive ageing in rats: we are evaluating the effects of enriched housing conditions on the decline of certain cognitive functions and are investigating the neurobiological correlates of successful ageing, focusing on the study of the cholinergic and endocannabinoid systems.

Neuroanatomy, pain and psychopathology

Leaders: Dr Pierre-Eric LUTZ, Dr Ipek YALCIN, Dr Michel BARROT, Dr Jennifer KAUFLING, Pr Pierre VEINANTE
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

Our team studies the role of epigenetic mechanisms in psychiatric diseases, in particular anxiety-depressive disorders and addictions, especially when they originate from chronic pain. In humans, we conduct studies of molecular biomarkers of these pathologies. In mice, we develop and use genetic and behavioral models. In both cases, epigenetic plasticity is studied using high-throughput sequencing, bioinformatics and high performance computing to better understand the polygenic mechanisms of these diseases.

Circadian clocks and metabolism

Leader: Dr. Étienne CHALLET
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

In the framework of an FRM collaborative project led by Chantal Mathis (ENGRAM team), our team is seeking to understand the mechanisms underlying circadian alterations in a mouse model of Alzheimer's disease.

Central and peripheral mechanisms of neurodegeneration

Responsable : Dr Luc DUPUIS
Unité de recherche : unité Inserm "Mécanismes centraux et périphériques de la neurodégénérescence" UMR_S 1118

Our laboratory aims at deciphering the pathological mechanisms that trigger Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia, two closely related fatal and currently untractable neurodegenerative diseases. Our originality lies in the study of the reciprocal interactions that occur between the central nervous system and the peripheral organs, and the general aim of understanding the myriad of signs and symptoms associated with these diseases.

Light, vision and the brain

Leaders: Dr. Marie-Paule FELDER-SCHMITTBUHL et Dr. Frank PFRIEGER
Research unit: Institute of Cellular and Integrative Neuroscience (INCI) UPR 3212

Our team studies the molecular and cellular mechanisms underlying neurodegeneration in the retina and in a rare disease, Niemann-Pick type C, for which the retina serves as a model. In particular, we are implementing methods for monitoring degeneration in vivo in retinal neurons, which will be used to develop therapeutic approaches.

Integrative Multimodal Imaging in Healthcare

Leader: Dr. Laura HARSAN
Research unit: Integrative Multimodal Imaging in Healthcare team (IMIS) within The Engineering science, computer science and imaging laboratory (iCube) UMR 7357

Neuroprotection in Multiple Sclerosis and Myelin-Related Peripheral Neuropathies

Leaders: Pr. Jérôme DE SEZE and Pr. Guy MENSAH-NYAGAN
Research unit: Inserm unit "Myelin biopathology, neuroprotection and therapeutic strategies" UMR_S 1119

The objective of the laboratory is to generate preclinical and clinical data that can be used to develop effective neuroprotective strategies against neurological and neurodegenerative diseases (NDD), which constitute a major health problem. In the clinic, the neurologists of our Unit consult and treat mainly patients with multiple sclerosis (MS), Neuromyelitis Optica (NMO) or Peripheral Neuropathies (PN). Our laboratory research is therefore focused on preclinical and clinical models of PN (chemo-induced, CIDP, CMT1A), MS and NMO. The researchers of our Unit also have a strong experience in the field of neuroprotection using cellular and animal models of Alzheimer's disease (AD).

Myelin Biomarkers and Neuroprotection in Neurodegenerative Contexts

Leaders: Pr. Guy MENSAH-NYAGAN, Pr. Michel MAITRE et Dr. Christine PATTE-MENSAH
Research unit: Inserm unit "Myelin biopathology, neuroprotection and therapeutic strategies" UMR_S 1119

The objective of the laboratory is to generate preclinical and clinical data that can be used to develop effective neuroprotective strategies against neurological and neurodegenerative diseases (NDD), which constitute a major health problem. In the clinic, the neurologists of our Unit consult and treat mainly patients with multiple sclerosis (MS), Neuromyelitis Optica (NMO) or Peripheral Neuropathies (PN). Our laboratory research is therefore focused on preclinical and clinical models of PN (chemo-induced, CIDP, CMT1A), MS and NMO. The researchers of our Unit also have a strong experience in the field of neuroprotection using cellular and animal models of Alzheimer's disease (AD).

Medical Genetics Laboratory

Leader: Pr. Hélène DOLLFUS
Research unit: Laboratoire de génétique médicale (LGM) - UMR_S 1112

The starting point of our team is the clinical observation of patients suffering from rare diseases of genetic origin (Bardet-Biedl syndrome, Alström syndrome, ciliopathies, rare and ultra-rare sensory diseases and in particular ophthalmological diseases, Cockayne syndrome and related repair diseases, rare hereditary dental diseases. ...), to identify the genetic causes of their disease(s) and to study the pathophysiological mechanisms at the cellular level and at the level of model organisms in order to arrive at therapeutic hypotheses opening the way to preclinical therapy projects and, ultimately, to return to the patient. The deep motivation, which drives the team, made up of both doctors and scientists, is based on our desire to develop truly translational research.

Laboratory of Pharmacology and Neurocardiovascular Toxicology (LPTNC) - UR 7296

Leader: Pr. Laurent MONASSIER
Research unit: Laboratoire de Pharmacologie et de Toxicologie Neurocardiovasculaire (LPTN) UR 7296

Our laboratory is specialised in pharmacological approaches to the serotonin system for various pathologies such as cardiac valve degeneration but also in the development of analytical systems for the detection of various synthetic substances including serotonin agonists of the synthetic cathinone family, used as hallucinogens. Our work in neurodegenerative diseases focuses on the involvement of this system in the regulation of the permeability of the blood-brain barrier and the possibilities offered by its modulation to promote the clearance of beta-amyloid from the central nervous system while limiting its penetration from the periphery. Our team is thus approaching an original facet of the treatment of neurodegenerative diseases through the regulation of the vascular permeability of the important capillary bed that vascularises the brain.

Channel receptors and their neuromediators: from biophysics to the development of opto-neuro-pharmacological tools for in vivo studies

Leader: Dr. Thomas GRUTTER
Research unit: Chemistry and Molecular Neurobiology team (CNM) within the Laboratory of Design and Application of Bioactive Molecules (LCAMB) UMR 7199

We work on ion channels (Piezo) and receptor channels (P2X) involved in many neurophysiological processes (pain, neurotransmission, sensory pathways). We study structure-function relationships and biophysical aspects and we design new molecular and chemical tools to better understand their mechanism of action. These tools also allow us to control the activity of these channels orthogonally in vivo. Dysfunction of these channels or channel receptors can trigger chronic pain or promote neurodegenerative diseases, such as Alzheimer's disease.