Affiliations: [a] Department of Physiology, Faculty of Medicine, Universitat de València, Valencia, Spain
| [b] Department of Anatomy and Human Embriology, Faculty of Medicine, Universitat de València, Valencia, Spain
| [c] Department of Psychobiology, Faculty of Psycology, Universitat de València, Valencia, Spain
| [d] Neonatal Research Group, Health Research Institut LaFe, Valencia, Spain
| [e] Department of Computer Science, School of Engineering ETSE, Universitat de València, Burjassot, Spain
Correspondence:
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Correspondence to: Prof. Ana Lloret, Department of Physiology, Faculty of Medicine, Universitat de València, Avda. Blasco Ibañez, 15, 46010 Valencia, Spain. Tel.: +34 963864154; E-mail: [email protected].
Abstract: Glutamate excitotoxicity has long been related to Alzheimer’s disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we observed a decrease in the AMPA receptor subunit GluA1 and they had impaired long-term potentiation. The Hebb-Williams Maze revealed that they had memory deficits. We show here for the first time that oral MSG supplementation can accelerate AD-like pathophysiology in a mouse model of AD.
