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- Title
Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory.
- Authors
Palmeri, Agostino; Ricciarelli, Roberta; Gulisano, Walter; Rivera, Daniela; Rebosio, Claudia; Calcagno, Elisa; Tropea, Maria Rosaria; Conti, Silvia; Das, Utpal; Roy, Subhojit; Pronzato, Maria Adelaide; Arancio, Ottavio; Fedele, Ernesto; Puzzo, Daniela
- Abstract
High levels of amyloid-β peptide (Aβ) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of Aβ are necessary for long-term potentiation (LTP) and memory. Because cGMP plays a key role in these processes, here we investigated whether the cyclic nucleotide cGMP influences Aβ levels and function during LTP and memory. We demonstrate that the increase of cGMP levels by the phosphodiesterase-5 inhibitors sildenafil and vardenafil induces a parallel release of Aβ due to a change in the approximation of amyloid precursor protein (APP) and the β-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking Aβ function, by using anti-murine Aβ antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates Aβ levels in the healthy brain which, in turn, boosts synaptic plasticity and memory.
- Subjects
AMYLOID beta-protein; ETIOLOGY of Alzheimer's disease; ALZHEIMER'S disease treatment; MEMORY; AMYLOID beta-protein precursor; AMYLOID beta-protein precursor genetics
- Publication
Journal of Neuroscience, 2017, Vol 37, Issue 29, p6926
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3607-16.2017