Administration     Physiologie Recherche Master
L'EA 4324  ORPHY (Optimisation des Régulations Physiologiques) étudie les mécanismes physiologiques participant ŕ l’optimisation des interactions organismes-milieu  Physiology Research Master  

Ongoing projects

Experimentations in progress


 Metabolism of reactive oxygen species, ROS (comparative approach: fish and rat)

 

This research topic concerns the relation between metabolic rate and ROS production which is regulated by anti-oxidant systems. This relation and its changes are studied in the context of the animal adaptation to environmental factors (temperature, pressure, exercise) and are related to the capacity to maintain or to develop a performance.

 

These mechanisms are studied in vitro and in vivo respectively at the cellular (mitochondria and muscular permeabilized fibres) and  tissular levels (muscle, liver). Some approaches are developed in our lab:

 

  •  In a comparative physiology approach of the above mechanisms, species (fish and rat) used  have different metabolic rate and temperature behaviour (ectotherm/endotherm)
  • The place of ROS in the optimization of energetic metabolism is more precisely studied in fish which presents a metabolic rate dependent from environment. Our lab investigates in eel the metabolic aspects at cellular level in terms of energetic cost and efficiency. Indeed, the eel (Anguilla anguilla) is an interesting model because it presents physiological (resistance to hypoxia, metamorphosis processes, swimming efficiency) and ecophysiological particularities. More precisely, during its life, eel performs a long migration which exposes it to several environmental factors (temperature, luminosity, pressure) susceptible to act as pro or antioxidant .

ROS production by mitochondria

 

 

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 Cell volume regulation (fish, rat)

 



Turbot hepatocytes

The maintenance of constant volume is a homeostatic imperative in animal cells. Indeed, cell volume perturbations and changes in cell water content affect the concentration of messenger molecules and disturb the complex signalling network that is crucial for cell functioning. Moreover, there is evidence suggesting a signalling role of cell volume itself in a variety of situations, from regulation of metabolic reactions to receptor recycling, hormone secretion, cell proliferation and in cell death. Whatever the cause of volume perturbation, cells respond by mechanisms of volume adjustment and, Regulatory Volume Decrease process (RVD) triggered by hypo-osmotic stimulation of cells constitutes a practical and interesting tool for the study of all signalling pathways and factors typically involved in physiological cellular responses.  Mechanism of RVD can be divided into three main steps: 

 

  • the detection of transient changes in cell volume by volume sensors
  • the transduction of this signal through the activation of signalling cascades
  • the regulation and/or activation of osmolyte extrusion pathways

In that context, our objective is to characterize these three steps in fish cells which represent suited model systems for these studies and to determine interactions between environmental changes and cell volume regulation ability.  

 

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Energetic metabolism and hydrostatic pressure (fish)

 

During its migration for reproduction the European eel (Anguilla anguilla) must cope with several extreme conditions: temperature (medium in the rivers, low in the oceans), salinity      (from fresh water to sea water), fasting ( the eel eats in the river but not during migration) and finally pressure (migration is performed at depth). The energy requirement due to the migration is very high (swimming activity, gonads development and gametogenesis) which let few possibilities for extra physiological activities because the energy budget is restrained to the fish fat stores. Under such environmental conditions whose the effects can interact, is there a hierarchy in the physiological functions? Are these functions optimised? Is the fish able to cope with a new stressing conditions?

For both sexes, the interactions of different factors such as pressure, temperature, swimming, salinity are studied in terms of energy metabolism.



Hyper chamber

 

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Cardiovascular risk factors  (rat)

 

Improvement of endothelial function by physical activity is well documented in human as well as animal models. Data from our and other research groups indicate that training improves endothelium-dependent relaxation in a frequency dependent manner, while intensity should be limited to 50-65% of maximal oxygen uptake. Conversely, the type of aerobic activities (concentric vs eccentric) has no influence. Finally, in healthy animals, we did not find any interaction between the acute effects of physical activity and those of a diet enriched with omega-3 polyunsaturated fatty acids. We are now investigating mecanisms involved in secondary prevention of endothelial dysfunction. Beneficial effects of physical activity are more pronouced in subjects with impaired endothelial function. Indeed, in spontaneously hypertensive rats (SHR, a model of essential hypertension), physical training restores endothelium-dependent vasorelaxation. We are currently studying the interactions between cardiométabolic risks factors, such as physical activity / nutrition / metabolic syndrome.

 

 

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 Sepsis

 

Sepsis remains the first cause of mortality in intensive care units despite the large amount of research conducted over the last twenty years. Sepsis is a pathological state associated with a systemic inflammatory reaction resulting from an infection. The difficulty in grasping sepsis lies in the fact that it is  multifactorial and involves several interacting physiological mechanisms : inflammatory, cardiovascular, endothelial, haemostatic, mitochondrial energetic metabolism ...
Sepsis is associated with a dysfunction of the vascular endothelium associated with oxidative stress, hypercoagulation and hypoperfusion. In many cases, it results in organs failure (severe sepsis) and, ultimately, in a stage of septic shock.

One of our objectives is to investigate the role of the vascular endothelium in the evolution of sepsis from a localized inflammation to a fully developed septic shock. To reach that goal, we validate a standardized procedure using an instrumented rat akin to human patient clinical take care. This rat experimental model allows blood sampling (for acid-base analyses and serum biomarkers assays) and measures of cardiovascular activity (heart rate , blood pressure, blood flow), ventilatory rate and  oxygen blood saturation level. Moreover, rings of the thoracic aorta are dissected for motricity tests to evaluate endothelial dysfunction. In the long run, we hope to able to reveal specific markers of sepsis and therefore improve current diagnostic abilities.
Moreover, we have shown that body temperature  plays a key role in the evolution of sepsis. The current work aims at improving therapeutic care through the use of body temperature control.
Within the next few years, we intend to apply our standardized experimental model to drug testing and more particularly to specify their  mode of action.

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 Hemorrhage and trauma

About 10% of worldwide deaths are due to traumas and 30 to 40% of those are linked to hemorrhage. During a state of hemorrhagic shock, a persistent systemic tissue hypoxia due to hypovolemia and loss of red blood cells is observed. To compensate for the lack of oxygen at tissue level, the anaerobic metabolism is activated. A lactic acidosis, the production of ROS and protons are observed thereby inducing inflammation and cell death the consequence of which can provoke patient death. Enhancing tissue oxygenation in case of hemorrhagic shock is paramount when treating patients. Hence, with Pr Y. Ozier and within the development of the trauma center (O. Grimault), our objective is to improve knowledge of the physiopathological mechanisms involved in the evolution of the hemorrhagic shock and therefore to acquire new means of diagnostic, thereby improving patient care.  
ORPHY Laboratory has developed murine models of hemorrhagic shock and trauma. They allow to study the consequences of these shocks on tissue metabolism and vascular function as well as to analyse the kinetic implementation of the shock. Taking that into account, different treatment modalities are tested with a specific focus on blood substitutes. We therefore explore the efficiency of Hemoxycarrier HM-101 (extracellular haemoglobin of Arenicola marina developed by Hemarina Society) during the treatment of hemorrhagic shock.

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Laboratoire ORPHY
UFR Sciences et Techniques, Université de Bretagne Occidentale

6 Av. Le Gorgeu  -  CS 93837
  29238 BREST Cedex 3   -   FRANCE

Directrice : C.MOISAN (+332.98.01.62.63)
Directrice adjointe: M-A.GIROUX-METGES(+332.98.01.80.67)
recherche@physiology-orphy.fr

 


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