Neuropeptides et Néprilysines : rôle dans la mémoire chez la Drosophile

Abstract : During my PhD, I studied neprilysins, proteinases known to degrade small neuropeptides, in particular mammalian amyloid-β peptides (Aβ). During Alzheimer’s disease, Aβ peptides aggregate to form toxic plaques. It has been shown that neprilysins expression modulates toxic effects of Aβ on memory in murine models of the disease. However, the role of neprilysins in memory under physiological conditions is still unknown. Drosophila expresses 4 neprilysins in the adult central nervous system. First we have analyzed their role in olfactive memory. We have shown that all of them are required for 2 specific memory phases: Middle-Term Memory (MTM) and Long-Term Memory (LTM). We also have identified the neurons in which they are required: the Mushroom Bodies (MB) and a pair of afferent neurons, the Dorsal Paired Medial (DPM) neurons. Then we investigated whether Aβ peptides could be one of the neprilysins’ targets. We have shown that Aβ expression in DPM neurons alters MTM only when Nep1 expression is inhibited. Furthermore, the LTM deficit of flies expressing Aβ in DPM neurons is rescued by Nep1 overexpression. To conclude, our results suggest that Nep1 degrades endogenous Aβ peptides during memory processes, and that Aβ is a physiological target for Nep1 under non-pathological condition.Finally, we became interested in the amnesiac neuropeptide, described as being required for memory in DPM neurons. Our work shows that amnesiac is actually required in DPM neurons for their development, and in the MB of adult flies in order to activate the adenylate cyclase responsible for coincidence detection leading to MTM formation.
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Oriane Turrel. Neuropeptides et Néprilysines : rôle dans la mémoire chez la Drosophile. Neurosciences [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066274⟩. ⟨tel-02300838⟩

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