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Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the Aβ 25-35 non-transgenic mouse model of Alzheimer’s disease

Abstract : Erythropoietin (EPO) promotes neurogenesis and neuroprotection. We here compared the protection induced by two EPO formulations in a rodent model of Alzheimer's disease (AD): rHu-EPO and a low sialic form, Neuro-EPO. We used the intracerebroventricular administration of aggregated Aβ₂₅₋₃₅ peptide, a non-transgenic AD model. rHu-EPO was tested at 125-500 µg/kg intraperitoneally and Neuro-EPO at 62-250 µg/kg intranasally (IN). Behavioural procedures included spontaneous alternation, passive avoidance, water-maze and object recognition, to address spatial and non-spatial, short- and long-term memories. Biochemical markers of Aβ₂₅₋₃₅ toxicity in the mouse hippocampus were examined and cell loss in the CA1 layer was determined. rHu-EPO and Neuro-EPO led to a significant prevention of Aβ₂₅₋₃₅-induced learning deficits. Both EPO formulations prevented the induction of lipid peroxidation in the hippocampus, showing an antioxidant activity. rHu-EPO (250 µg/kg) or Neuro-EPO (125 µg/kg) prevented the Aβ₂₅₋₃₅-induced increase in Bax level, TNFα and IL-1β production and decrease in Akt activation. A significant prevention of the Aβ₂₅₋₃₅-induced cell loss in CA1 was also observed. EPO is neuroprotective in the Aβ₂₅₋₃₅ AD model, confirming its potential as an endogenous neuroprotection system that could be boosted for therapeutic efficacy. We here identified a new IN formulation of EPO showing high neuroprotective activity. Considering its efficacy, ease and safety, IN Neuro-EPO is a new promising therapeutic agent in AD.
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Journal articles
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https://www.hal.inserm.fr/inserm-02462908
Contributor : Catherine Desrumaux <>
Submitted on : Friday, January 31, 2020 - 3:39:47 PM
Last modification on : Saturday, February 15, 2020 - 1:34:50 AM

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Tangui Maurice, Muhammad-Hariri Mustafa, Catherine Desrumaux, Emeline Keller, Gaëlle Naert, et al.. Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the Aβ 25-35 non-transgenic mouse model of Alzheimer’s disease. Journal of Psychopharmacology, SAGE Publications, 2013, 27 (11), pp.1044-1057. ⟨10.1177/0269881113494939⟩. ⟨inserm-02462908⟩

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