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Communication Dans Un Congrès Année : 2019

Cognition, hippocampus and neurolupus

Résumé

Characterized by cognitive dysfunctions and emotional disturbances, neurolupus is a severe manifestation of systemic lupus erythematosus, an inflammatory autoimmune polymorphic syndrome. Patients diagnosed with this pathology face a poor prognosis and suffer from treatment regimens prone to debilitating secondary effects. In the absence of a selective therapy and in the search for potential molecular targets specific to neurolupus, we conducted studies on a murine model, the MRL/lpr strain, that develops an accelerated form of lupus-like disease. Compared to MRL+/+ littermates, MRL/lpr mice display (i) higher proteinuria levels (P≤0.05), which confirms the presence of an active systemic disease, (ii) reduced brain weight (P≤0.01) and (iii) cerebral infiltration of immune cells (P≤0.001), which indicate cerebral atrophy and active neuroinflammatory mechanisms. Behaviorally, MRL/lpr mice are significantly impaired in the Y-maze and the T-maze (P≤0.05 and P≤0.01, respectively) likely reflecting a hippocampal failure. Congruently, Nissl staining shows neuronal loss and/or degeneration in the hippocampus of diseased MRL/lpr mice. In my ongoing studies, I am exploring which hippocampal regions are more specifically affected. Furthermore, since implication of a metabolically active process that maintains cellular homeostasis, called autophagy, has been recently described both in proper formation of hippocampal neuronal circuits and as a possible therapeutic target for treatment of lupus, I am hence investigating how autophagy might be engaged in neurolupus by observing LC3B autophagic marker expression in affected hippocampi. Indeed, autophagy is deregulated in immune cells in the blood of lupus patients and MRL/lpr mice, however such dysfunction remains to be confirmed in the case of central nervous system disease. In conclusion, MRL/lpr substrain is a suitable model for the study of neurolupus and research for therapeutic targets with autophagy as a promising candidate.

Domaines

Immunologie
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Dates et versions

hal-02935008 , version 1 (09-09-2020)

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  • HAL Id : hal-02935008 , version 1

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Mykolas Bendorius, Sylviane Muller, Hélène Jeltsch-David. Cognition, hippocampus and neurolupus. Les Journées du Campus d’Illkirch 2019, Apr 2019, Illkirch, France. ⟨hal-02935008⟩

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