In the central nervous system, oligodendroglial cells represent an abundant cell population with critical functions, as they sense, regulate, and provide insulation and trophic support to neurons. From oligodendrocyte progenitor cells (OPCs) to myelinating oligodendrocytes (OLs), the oligodendroglial lineage is therefore crucial for normal neurological functions, such as brain plasticity.
With age, in parallel with a profound decline of cognitive abilities, oligodendroglial capacities have been shown to decline. Defective myelination has been attributed to age-related epigenomic, transcriptomic and phenotypic changes in adult oligodendroglial cells, affecting their myelinating properties.
Our lab objectives are to better understand the role of oligodendroglial cells in the central nervous system, and how their functions are dysregulated in aging and in age-related diseases. By leveraging epigenetic activators, we aim at rejuvenating old oligodendroglial cells, to prevent the onset of neurological deficits normally associated with aging.
Our team works on a specific non-neuronal cell type, the oligodendroglial cell lineage, which is populating the brain and spinal cord. Oligodendroglial cells are crucial for brain functions, as they provide insulation and metabolic support to the neurons, essential for neuronal activity. They are also important for memory and learning functions, as they participate in neuronal network consolidation. However, with age, these oligodendroglial cells don't work as well as they used to. This decline in their abilities correlates with a decline in our cognitive abilities, like memory and learning skills. Our main goal is to better understand how aging affects oligodendroglial cells, and how this can directly affect our behavior and mental abilities. We want to develop new tools to rescue the properties of oligodendroglial cells, thus improve brain function in aging and in diseases like Alzheimer's Disease.
How age-related changes in the oligodendroglial lineage directly impact cognitive function in aging?
If neuronal circuits are the base of brain organization, an accumulation of evidence has now highlighted the role of oligodendroglial cells in brain plasticity. However, how age-related changes in oligodendroglial cells might explain cognitive deficits during aging is still unknown.
By challenging our aging-like oligodendroglial-specific mouse model with a battery of behavioral assays, we address the role of oligodendroglial cells in cognitive decline.
How age-related dysfunctions in oligodendroglial cells could directly drive neurodegeneration susceptibility and disease onset?
Recently, an accumulation of evidence has highlighted the role of glial cells in a myriad of neurological, neurodegenerative and psychiatric diseases. However, the role of oligodendroglial cell lineage in the pathogenesis of pathology, such as Alzheimer’s Disease, remains largely unknown.
By combining transcriptomic approaches and behavioral assays, we decode how oligodendroglial cells contribute to the pathogenetic onset of psychiatric and neurodegenerative diseases.
How age-related changes in the oligodendroglial lineage directly impact neuro-oligodendroglial communication?
The cross-talk between oligodendroglial cells and other cell types in the central nervous system, especially neurons, is essential for brain plasticity and cognitive functions.
By characterizing the molecular mechanisms that regulate neuro-oligodendroglial interaction, from a specific oligodendroglial point of view, we highlight novel oligodendroglial functions in cell-cell communication, and their dysregulations in aging and age-related diseases.
Development of translational strategies to rejuvenate oligodendroglial cells and improve brain cognition in aging and disease.
Currently, we are still lacking strategies to rejuvenate the brain and maintain longer neurological functions in aging and age-related diseases. Our better understanding of adult oligodendroglial proprieties is a crucial first step towards the development of strategies to rescue myelin plasticity and repair capacity with age.
We are leveraging epigenetic activators known to be dysregulated in aging, in combination with non-invasive delivery tools, to reactivate cells in our aging and disease models.
