Since 2012, I have developed with Joëlle Chabry and Agnès Petit a theme about the beneficial effects of environmental enrichment in the treatment of depression, in the team of Catherine Heurteaux at the IPMC.

I became interested in the more neuro-immunological aspects of this project by studying more precisely the role of microglia and T cells in the antidepressant effects of environmental enrichment. This project allowed me to use both my knowledge of neuro-immunology and my skills in electrophysiology, and I benefited from all the techniques available in the laboratory. For this project, I have also established numerous collaborations within the IPMC with notably Nicolas Glaichenhaus's teams (immunologist) but also outside the IPMC in France and abroad.

​

      Depression is accompanied by structural and neurochemical changes in the brain, particularly within the limbic system, in particular the hippocampus, including a decrease in its overall volume, a reduction in neurogenesis and synaptogenesis, and synaptic plasticity. There are also changes in the activity of mono-aminergic systems, particularly serotoninergic in the Raphé nuclei, dysregulation of the hypothalamic-pituitary-adrenal axis and neuroinflammation. The classical treatments for depression rely mainly on the modulation of mono-aminergic neurotransmission systems, but these treatments have limitations and disadvantages, in particular a long delay in action and resistance to treatment in many patients.

​

      In addition to the pharmacological approach, another strategy to combat depression in humans is the use of behavioral therapies: increased physical activity, sensory stimulation and social interaction would have beneficial effects in patients depressive. In mice, the enriched environment model that is to say stimulant without being stressful, limits the anxio-depressive syndromes induced for example by prolonged treatment with corticosterone, the stress hormone in mice. Depression is accompanied by neuroinflammation. Different cell populations contribute to inflammation of the central nervous system, including resident immune cells of the brain (microglia and perivascular macrophages) and infiltrating immune cells (inflammatory and neutrophilic monocytes). The cytokines produced by these cells can by altering the activity of the neural networks lead to a depressive state.

      In the first part of our work, we have shown that one of the mediators of the beneficial effects of EE is an adipokine (hormone produced by adipose tissue), adiponectin, which by its anti-inflammatory effects on microglia and resident macrophages has beneficial effects on the depressive anxiety behavior of mice. We have shown the antidepressant properties of an adiponectin receptor agonist called adiporon, for which we have filed a patent.       We went further by developing the novel idea that T cells also might play a role in depression, but a beneficial role in promoting plasticity and we investigated the mechanisms by which CD8 + and CD4 + T cells selectively affect the brain plasticity.