PPSN - EA 4674

Physiology and Physiopathology of the Somatomotor and autonomous Nervous system

Director : Jérôme TROUSLARD

Campus Saint-Jérôme – Case 351
52 Avenue Escadrille Normandie Niemen
F-13397 Marseille CEDEX 20
France

Located on the St Jérôme Campus, the Laboratory of Physiology and physiopathology  of the autonomous nervous system (PPSN, EA 4674) regroups 3 research teams and hosts a young Startup in biotechnology (Biomeostasis).

Pictures from the PPSN laboratory

The research teams

All PPSN research teams are affiliated to the neuroscience master’s program and can thus train neuroscience master’s students and offer them projects to apply for a Ph.D. scholarship.

Nervous system and liquid compartment interactions (Jérôme Trouslard)

1. Physiology of neurons that contact the cerebrospinal fluid

Neurons that contact the cerebrospinal fluid exist at the ependymal layer of the central canal of the brain stem and spinal cord. Although they are present in all vertebrates, their functions remain unknown, including their roles in the spinal neurogenic niche. These neurons express PKD2L1, a protein forming a cationic channel sensitive to pH and osmolarity, which would correspond to sensory functions. At the spinal cord level, these neurons have preserved some immaturity and migration characteristics, and could thus constitute an important neuron reservoir alternative to neurogenesis which is very limited at the spinal cord level. We are now characterizing their responses to hormones and neurotransmitters present in the cerebrospinal fluid and the network in which these neurons are inserted

2. Role of microRNAs in energy homeostasis

Hypothalamic neurons expressing pro-opiomelanocortin (POMC) play an important role in the central control of energy balance. These neurons integrate several nervous and hormonal messengers, including leptin, which reflects the state of energy reserves. The role of microRNAs (non-coding RNAs that regulate gene expression) in the regulation of energy balance at a central level needs to be clarified. We identified in silico microRNAs potentially targeting POMC mRNA and showed that the hypothalamic expression of 3 microRNAs (miR-383, miR-384-3p, and miR-488) was increased in obese mice deficient for leptin (ob / ob) or its receptor (db / db). Our results highlight the involvement of microRNAs in the modulation of POMC expression downstream of leptin signaling.

Members

Jérôme TROUSLARD, Anne KASTNER, Lourdes MOUNIEN, Riad  SEDDIK, Nicolas WANAVERBECQ, Adel DERGHAL, Ghizlane ER-RAOUI, Nina JURCIC. Total: 2 HDRs.

Research axes

  • Physiology of neurons that contact the cerebrospinal fluid
  • Role of microRNAs in energy homeostasis

Techniques:

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Pharmacology
  • Animal behavior

Keywords

Cerebrospinal fluid, brainstem, spinal cord, hypothalamus, PKD2L1, pH, synaptic transmission, GABA, pro-opiomelanocortin (POMC), energy balance, leptin

Animal cognition and behavior - Excitability, synaptic transmission, network functions - Motor systems - Sensory systems - Sleep, autonomic and neuroendocrine systems

Molecular Interactions in Model and Biological Membrane Systems (Nouara Yahi, Jacques Fantini)

The main thematic of our group is dedicated to the elucidation of the role played by brain lipids (gangliosides and cholesterol) in the formation of neurotoxic oligomers of amyloid proteins (amyloid pores). We have elucidated the biochemical code controlling the binding of gangliosides to amyloid proteins. On the basis of this discovery, we have designed a chimeric peptide able to block the formation of amyloid pores in the context of Alzheimer’s and Parkinson’s diseases. Because it binds to all brain gangliosides, our chimeric peptide competitively inhibits the binding of amyloid proteins to their respective ganglioside receptor (GM1 for Alzheimer and GM3 for Parkinson). Correspondingly, the neurotoxic effects induced by amyloid pores are blocked by nanomolar concentrations of chimeric peptide. We have thus developed a new therapeutic strategy for the treatment of various neurodegenerative diseases and synthesized the first universal “anti-amyloid pore” molecule. A gene therapy approach based on our chimeric peptide is also developed by our group. An international patent describing this invention covers a broad range of ganglioside-associated pathologies including viral, bacterial and parasite infections as well as brain metastasis of peripheral tumors.

 

Members

Nouara YAHI, Jacques FANTINI, Henri CHAHINIAN, Coralie DI SCALA. Total: 2 HDRs.

Research axes

Molecular mechanisms of the neurotoxicity of amyloid oligomers

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Calcium imaging
  • Bioinformatics
  • Molecular modelling

Keywords

Alzheimer’s disease, Parkinson’s disease, cholesterol, gangliosides, oligomers, therapy

Disorders of the nervous system - Human cognition and behavior - Novel methods and technology development

Feeding behaviour and energy homeostasis disorders (Jean-Denis Troadec)

The team works on the regulation of feeding behavior and associated energetic disorders (obesity, anorexia, cachexia) by characterizing the non-neuronal and neuronal mechanisms operating at the level of the bulbar and hypothalamic structures.

Our team projects are based on general physiology approaches and functional exploration (eating behavior, calorimetry, telemetry, forced feeding, stereotactic surgery, electrophysiology). The team has mouse models with energy imbalance either induced (diet, inflammation) or genetic (KO models). Cell biology techniques (cell culture, Western blotting) and molecular techniques (qPCR) complete our analysis potential.

Members

Jean-Denis TROADEC, Anne ABYSIQUE, Rym BARBOUCHE, Michel DALLAPORTA, Stéphanie GAIGE (RAMI), Florent GUILLEBAUD, Bruno LEBRUN, Clément PIERRE.

Research axes

  • Determining the contribution of the glial compartment of the hypothalamus and brainstem in the regulation of food intake and glucose homeostasis
  • Characterizing the involvement of peptides in energy homeostasis
  • Testing the efficacy of peptides in the treatment of diet-induced obesity.

Techniques

  • Biochemistry
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Indirect calorimetry

Keywords

Food intake, obesity, glia, connexin 43, hypothalamus, brainstem

Animal cognition and behavior - Disorders of the nervous system - Sleep, autonomic and neuroendocrine systems
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