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Encéphalites à anticorps anti-NMDAR : étude clinique et mécanistique

Abstract : Anti-NMDAR autoimmune encephalitis is a newly described pathology, characterized by the presence of IgG antibodies (Abs) directed against NMDA receptor (NMDAR). Glutamatergic synapses are the main component of excitatory transmission in the adult brain and the ionotropic glutamate receptor NMDAR has a key role in synaptic plasticity. Synaptic plasticity is defined by the synapses property to modify their transmission strength and seems to be the cellular correlate of learning and memory. In vitro and in vivo studies on anti-NMDAR Abs effects showed an altered dynamic at the membrane followed by an internalization of NMDAR. Thus, Abs seem to have a pathogenic effect, able to explain clinical symptoms. During my thesis, I wanted to deepen the understanding of this pathology on the clinical and mechanistic level. To this end, I studied the clinical and histological features of patients with an associated tumor. Results obtained allow me to establish management recommendations considering the high mortality rate in these patients and a higher frequency of immature ovarian teratomas than in the general population. Simultaneously, I studied the effect of anti-NMDAR Abs on synaptic transmission and plasticity in a murine model allowing chronic Abs infusion. These results obtained by electrophysiology on acute slices allowed me to demonstrate an effect of CSF Abs on synaptic plasticity but of less amplitude that the in vitro studies had suggested. Results also highlighted the importance of the duration to antibodies exposure
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Submitted on : Wednesday, April 18, 2018 - 10:59:28 AM
Last modification on : Thursday, February 6, 2020 - 10:56:02 AM

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Chloé Bost. Encéphalites à anticorps anti-NMDAR : étude clinique et mécanistique. Neurobiologie. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1204⟩. ⟨tel-01769588⟩

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