Amyloid-β Peptide Is Needed for cGMP-Induced Long-Term Potentiation and Memory

被引：65

作者：

Palmeri, Agostino ^{[1
]}

Ricciarelli, Roberta ^{[2
]}

Gulisano, Walter ^{[1
]}

Rivera, Daniela ^{[2
]}

Rebosio, Claudia ^{[3
]}

Calcagno, Elisa ^{[2
]}

Tropea, Maria Rosaria ^{[1
]}

Conti, Silvia ^{[9
,10
]}

Das, Utpal ^{[5
,6
]}

Roy, Subhojit ^{[5
,6
,7
,8
]}

Pronzato, Maria Adelaide ^{[2
]}

Arancio, Ottavio ^{[9
,10
]}

Fedele, Ernesto ^{[3
,4
]}

Puzzo, Daniela ^{[1
]}

机构：

[1] Univ Catania, Physiol Sect, Dept Biomed & Biotechnol Sci, Via S Sofia 89, I-95123 Catania, Italy

[2] Univ Genoa, Sch Med & Pharmaceut Sci, Sect Gen Pathol, Dept Expt Med, I-16132 Genoa, Italy

[3] Univ Genoa, Sch Med & Pharmaceut Sci, Sect Pharmacol & Toxicol, Dept Pharm, I-16148 Genoa, Italy

[4] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy

[5] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[7] Univ Wisconsin, Dept Pathol, Madison, WI 53705 USA

[8] Univ Wisconsin, Dept Neurosci, Madison, WI 53705 USA

[9] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[10] Columbia Univ, Taub Inst, New York, NY 10032 USA

来源：

JOURNAL OF NEUROSCIENCE | 2017年 / 37卷 / 29期

基金：

美国国家卫生研究院;

关键词：

amyloid beta; APP; cGMP; long-term potentiation; memory; synaptic plasticity; HIPPOCAMPAL SYNAPTIC PLASTICITY; CYCLIC ADENOSINE-MONOPHOSPHATE; DEPENDENT PROTEIN-KINASE; APP/PS1 TRANSGENIC MICE; DISEASE MOUSE MODEL; ALZHEIMERS-DISEASE; GUANYLYL CYCLASE; IN-VIVO; APP; INHIBITION;

D O I：

10.1523/JNEUROSCI.3607-16.2017

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

High levels of amyloid-beta peptide (A beta) have been related to Alzheimer's disease pathogenesis. However, in the healthy brain, low physiologically relevant concentrations of A beta 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 A beta 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 A beta due to a change in the approximation of amyloid precursor protein (APP) and the beta-site APP cleaving enzyme 1. Moreover, electrophysiological and behavioral studies performed on animals of both sexes showed that blocking A beta function, by using anti-murine A beta antibodies or APP knock-out mice, prevents the cGMP-dependent enhancement of LTP and memory. Our data suggest that cGMP positively regulates A beta levels in the healthy brain which, in turn, boosts synaptic plasticity and memory.

引用

页码：6926 / 6937

页数：12

共 59 条

[1] Cyclic GMP-dependent protein kinase regulates the expression of thioredoxin and thioredoxin peroxidase-1 during hormesis in response to oxidative stress-induced apoptosis [J].