[en] Neuroinflammation and hippocampal synaptic plasticity during experimental autoimmune encephalomyelitis
It is now clear that the immune system plays an important role on neuronal functions like cognition and synaptic plasticity. A complex crosstalk takes place between neurons, glia and infiltrating immune cells to promote the remodeling of synaptic circuits. However, this system can be rapidly disrupted during inflammatory conditions inducing cognitive impairments by mechanisms still poorly understood. Immune responses are complex, being either neuroprotective or detrimental, and largely dependent on the context, the duration of the inflammatory process and the type of activated inflammatory cells. This project aims to study the impact of neuroinflammation on neuronal network activity and synaptic plasticity in mouse hippocampus and to highlight inflammatory actors related to cognitive disorders. Our analyses are performed during the course of EAE (experimental autoimmune encephalomyelitis), a model of CNS chronic inflammatory disease induced by a specific autoimmune reaction leading to demyelination and motor disorders. Electrophysiological recordings made on acute hippocampal slices from EAE mice revealed a higher synaptic plasticity at the peak of EAE but which decreases when motor symptoms improve (remission). A cognitive impairment was also demonstrated in vivo during this remission stage by the contextual fear conditionning. These results are not related to demyelination as no modification of MBP expression was found in EAE hippocampus by western-blotting and IHC. However, our immunostainings and ELISA experiments revealed a higher glial activation and a production of inflammatory factors like IL1beta in the hippocampus of EAE mice. So, microglia and astrocytes could contribute to modifications of hippocampal synaptic plasticity during EAE.
