Inrae, Bordeaux Neurocampus, France
Role of microglia in the deleterious effects of gestational inflammation on brain functioning
Maternal immune activation (MIA) disrupts the central innate immune system during a critical neurodevelopmental period. Microglia are primary innate immune cells in the brain although their direct influence on the MIA phenotype is largely unknown. I will present data indicating that MIA alters microglial gene expression associated to increased Neuron-microglia interactions, repetitive behavior, social deficits, and synaptic dysfunction to layer V intrinsically bursting pyramidal neurons in the prefrontal cortex of mice. Treating MIA offspring by colony stimulating factor 1 receptor inhibitors induces depletion and repopulation of microglia, and corrects protein expression of the newly identified MIA associated neuritogenic molecules in microglia, which coalesces with correction of MIA-associated synaptic, neurophysiological, and behavioral abnormalities. Going further we found a sex-dependent long-lasting pathological effect by MIA leading to abnormal behaviors including social and memory impairments. We also found a sex-dependent therapeutic effect of CSF1R inhibitor on sociability deficit in male mice and contextual memory impairment in both male and female mice while there was no obvious adverse effect in animal behavior by CSF1R inhibition. Our study demonstrates that maternal immune insults perturb microglial phenotypes and influence neuronal functions throughout adulthood, and reveals a potent effect of colony stimulating factor 1 receptor inhibitors on the correction of MIA-associated microglial, synaptic, and neurobehavioral dysfunctions.
He obtained his Ph.D. at the University of Bordeaux in 2012 on the effect of central inflammation on memory and its modulation by nutrition. He then studied the role of microglia in the deleterious effects of early-life-adversity (Yale University 2013-2016) and then moved to Boston University where he worked on two lines of research. On one hand he worked on understanding the role of microglia in the detrimental effects of gestational inflammation on brain functioning and on the other hand on the mechanisms of tau propagation in Alzheimer’s disease and how exosomes can participate in tau spread (2016-2020). He was recruited as an INRAE researcher at the NutriNeuro laboratory in France in 2020 and his current main interests are in relation to nutrition, microglia, aging and age-associated disorders. In particular he is interested in the role of exosomes in mediating or as a source of markers of age-associated cognitive decline and its modulation by nutrition.