When experts in obesity meet experts in memory
Cutting-edge translational research in obesity-linked memory deficits
Patients affected with metabolic disorders often exhibit alterations of their mnesic performances, more particularly at the level of memory flexibility.
A collaboration joining together experts of memory impairments and of metabolic disorders has been initiated on OptoPath platform to develop personalized memory tests for Obese, Diabetic or Cushing patients. These very accurate tests involve a virtual radial-maze and will assess for very early signs of memory flexibility impairment. They will be completed by further metabolic studies and fMRI imaging. The scientists will then move back to animal models to identify the molecular/intracellular changes occurring within the integrate network of memory systems,. For these studies to come to a full circle, extra fundings will be necessary to cover the expenses of such an ambitious project.
From the metabolic side, the collaboration involves Daniela Cota, OptoPath’s expert in energy balance and obesity studies, and her two colleagues, clinician scientists from Bordeaux hospital (Blandine Gatta and Antoine Tabarin).
From the memory side, it involves Nicole Etchamendy, OptoPath’s expert in declarative memory and mnemonic flexibility impairments in aging.
This multi-disciplinary partnership is a good example of the capacity of OptoPath to foster collaborative research on psychobehavioral dimensions that can be shared by the four OptoPath targets, i.e. Obesity, Memory deficits in aging, Drug Addiction and PTSD. In other words, OptoPath meets the conditions for transnosographic dimensional research.
The virtual radial maze to study impairment in memory flexibility : an exemplary case of translational research
During her post-doctoral studies at McGill University in the Laboratory of Human Spatial Memory, Navigation and Functional Plasticity, Nicole Etchamendy was developing research projects on animal models to improve understanding of aging-related memory declines. She was using behavioral tools previously developed by Aline Marighetto (1) to study declarative memory and mnemonic flexibility impairments. In these procedures, mice are trained in an open eight-arm radial maze to find food pellets, and tested for their ability to correctly use the information learned into novel situations, for example by changing the way of presenting arms. Nicole’s studies showed that aged mice and young adult mice with damaged hippocampus learned accurately the first step of a task which required them to learn a constant reward location in a specific set of arms. In contrast, in a second stage, they were impaired relative to healthy young adult mice when faced with rearrangements of the same arms (memory flexibility impairment). This procedure was proposed as a model of the selective declarative and relational memory decline classically described in elderly people (2).
To examine the validity of this hypothesis, Nicole and her collaborators decided to adapt this protocol to humans, using a virtual radial-maze. This is where Nicole’s spouse, a graphic designer passionate about new technologies and videogames, comes in. Using and modifying the virtual environments provided by a videogame, he helped the scientists to design complex virtual surroundings, mimicking for instance real landscapes around the maze arms. This virtual radial-maze has since become a very sensitive tool to assess specific features of memory flexibility in humans. Similarly to mice, participants need to learn and remember the location of hidden rewards by encoding the spatial relationship between the target object and environmental landmarks. Their memory flexibility is then challenged by modifications of the rewards locations. To make a long and complicated story short, the scientists demonstrated that older participants displayed a deficit in the performance of their memory flexibility, similar to the one previously described in aged mice. Functional magnetic resonance imaging (fMRI) subsequently demonstrated the respective roles of hippocampus and caudate nucleus in spatial or response strategies upon navigation in a virtual maze. (3).
This is a perfect example of translational research: adapt an innovative behavioral tool carefully validated in animal models to personalized human medicine.
When Nicole joined Aline’s Marighetto team at Neurocentre Magendie in Bordeaux, OptoPath’s industrial partner, Imetronic, created a 3D fully automated version of the virtual radial-maze, therefore enabling automated administration of the task, data recording and analysis on a large number of subjects.