title: Memantine prevents memory consolidation failure induced by soluble beta amyloid in rats.
abstract: It has been well documented that β-amyloid (Aβ) peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer's disease (AD). However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ) are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 μM), on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC) glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA) receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2 h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p), administered immediately after the familiarization trial (T1). On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of early cognitive impairment.
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Foggia Foggia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tucci
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Foggia Foggia, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mhillaj
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Foggia Foggia, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Morgese
authors.affiliation: Department of Pathology and Immunology, University of Geneva Geneva, Switzerland.
authors.forename: Marilena
authors.initials: M
authors.lastname: Colaianna
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Foggia Foggia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Zotti
authors.affiliation: Department of Mental Health and Psychiatry, Geneva University Hospital and University of Geneva Geneva, Switzerland.
authors.forename: Stefania
authors.initials: S
authors.lastname: Schiavone
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Foggia Foggia, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cicerale
authors.affiliation: Department of Sciences, University "Roma Tre" Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Trezza
authors.affiliation: Department of Physiology and Pharmacology, La Sapienza, University of Rome Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Campolongo
authors.affiliation: Department of Physiology and Pharmacology, La Sapienza, University of Rome Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cuomo
authors.affiliation: Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Foggia Foggia, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Trabace
keywords: glutamate; long term memory; memantine; short term memory; soluble beta amyloid