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

• Published in: Journal of psychopharmacology (Oxford) 2013-11, Vol.27 (11), p.1044-1057
• Main Authors: Maurice, Tangui, Mustafa, Muhammad-Hariri, Desrumaux, Catherine, Keller, Emeline, Naert, Gaëlle, García-Barceló, María de la C, Rodríguez Cruz, Yamila, Garcia Rodríguez, Julío César
• Format: Article
• Language: English
• Subjects: AKT protein; Life Sciences
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881113494939

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 Aβ 25-35 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 Aβ 25-35 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 Aβ 25-35 -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 Aβ 25-35 -induced increase in Bax level, TNFα and IL-1β production and decrease in Akt activation. A significant prevention of the Aβ 25-35 -induced cell loss in CA1 was also observed. EPO is neuroprotective in the Aβ 25-35 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.