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Communication Dans Un Congrès Année : 2018

Cognitive deficits in a murine model of lupus and effects of therapeutic peptide P140

Viviane Pallage
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Nicolas Schall
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Sylviane Muller
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Résumé

Lupus is frequently accompanied by behavioral deficits of unknown etiology, which are severe complications of the illness with no specific treatment. The aim of this study was to characterize the neurobehavioral outcomes of MRL/lpr mice, which develop an accelerated form of lupus-like disease, and to evaluate the effects of P140, a therapeutic phosphopeptide developed in our laboratory, on these defects. Motricity, anxiety-like behavior and cognitive function (T-maze alternation; task known for its sensitivity to hippocampal damage) have been evaluated in 60 female MRL mice (30 MRL/lpr and 30 MRL+/+ -used as controls- treated or not with P140). The serum levels of several cytokines were measured by ELISA, and at sacrifice, brain and spleen were collected and used for flow cytometry evaluation to check cellular infiltration. Neither overt manifestations (dermatitis, alopecia) nor premature deaths were seen. Compared to 17-week-old MRL+/+ controls, MRL/lpr mice display splenomegaly and increased proteinuria (normalized by P140), reduced brain weight (indicative of brain atrophy), and cerebral infiltration of lymphoid cells and macrophages. They show diurnal hyperactivity but no sensorimotor deficit nor clear-cut anxiety-like signs. However, we found that they are significantly impaired in alternation behavior, likely reflecting a hippocampal failure. This defect was totally compensated by P140 administration. Collectively, these data are in line with the view that hippocampal neurodegeneration, at least impaired hippocampal function, accompanies lupus disease. They also demonstrate that the peptide P140 exerts central effects with cognitive expression, and arouse hope for patients suffering from neurolupus for which there is nowadays no specific treatment.
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Dates et versions

hal-02935009 , version 1 (09-09-2020)

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  • HAL Id : hal-02935009 , version 1

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Helene Jeltsch-David, Viviane Pallage, Nicolas Schall, Sylviane Muller. Cognitive deficits in a murine model of lupus and effects of therapeutic peptide P140. 11th International Congress on Autoimmunity, May 2018, Lisbon, Portugal. ⟨hal-02935009⟩

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