Impaired TrkB receptor signaling contributes to memory impairment in APP/PS1 mice

被引：75

作者：

Kemppainen, Susanna ^{[1
]}

Rantamaki, Tomi ^{[2
]}

Jeronimo-Santos, Andre ^{[3
,4
]}

Lavasseur, Gregoire ^{[5
,6
]}

Autio, Henri ^{[2
]}

Karpova, Nina ^{[2
]}

Karkkainen, Elisa ^{[1
]}

Staven, Saara ^{[1
]}

Vicente Miranda, Hugo ^{[7
]}

Outeiro, Tiago F. ^{[7
,8
,9
]}

Diogenes, Maria J. ^{[3
,4
]}

Laroche, Serge ^{[5
,6
]}

Davis, Sabrina ^{[5
,6
]}

Sebastiao, Ana M. ^{[3
,4
]}

Castren, Eero ^{[2
]}

Tanila, Heikki ^{[1
,2
,10
]}

机构：

[1] Univ Eastern Finland, AI Virtanen Inst, Kuopio 70211, Finland

[2] Univ Helsinki, Ctr Neurosci, Helsinki, Finland

[3] Univ Lisbon, Inst Mol Med, Fac Med, Inst Pharmacol & Neurosci, P-1699 Lisbon, Portugal

[4] Univ Lisbon, Unit Neurosci, P-1699 Lisbon, Portugal

[5] CNRS, UMR 8195, F-91405 Orsay, France

[6] Univ Paris 11, Ctr Neurosci Paris Sud, UMR 8195, Orsay, France

[7] Inst Mol Med, Cell & Mol Neurosci Unit, Lisbon, Portugal

[8] Univ Lisbon, Fac Med, Inst Fisiol, P-1699 Lisbon, Portugal

[9] Univ Med Gottingen, Dept NeuroDegenerat & Restaurat Res, Gottingen, Germany

[10] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland

来源：

NEUROBIOLOGY OF AGING | 2012年 / 33卷 / 06期

基金：

芬兰科学院;

关键词：

BDNF; Tyrosine kinase receptor; Amyloid; Memory; Hyperactivity; APPSWE/PS1DE9 MOUSE MODEL; BETA-AMYLOID PEPTIDE; NEUROTROPHIC FACTOR; TRANSGENIC MICE; ALZHEIMERS-DISEASE; SPATIAL MEMORY; TRUNCATED TRKB.T1; FULL-LENGTH; IN-VIVO; DEPOSITION;

D O I：

10.1016/j.neurobiolaging.2011.11.006

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, learning, and memory. Levels of BDNF and its main receptor TrkB (TrkB.TK) have been reported to be decreased while the levels of the truncated TrkB (TrkB.T1) are increased in Alzheimer's disease. We show here that incubation with amyloid-beta increased TrkB.T1 receptor levels and decreased TrkB.TK levels in primary neurons. In vivo, APPswe/PS1dE9 transgenic mice (APdE9) showed an age-dependent relative increase in cortical but not hippocampal TrkB.T1 receptor levels compared with TrkB.TK. To investigate the role of TrkB isoforms in Alzheimer's disease, we crossed AP mice with mice overexpressing the truncated TrkB.T1 receptor (T1) or the full-length TrkB.TK isoform. Overexpression of TrkB.T1 in APdE9 mice exacerbated their spatial memory impairment while the overexpression of TrkB.TK alleviated it. These data suggest that amyloid-beta changes the ratio between TrkB isoforms in favor of the dominant-negative TrkB.T1 isoform both in vitro and in vivo and supports the role of BDNF signaling through TrkB in the pathophysiology and cognitive deficits of Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：1122.e23 / 1122.e39

页数：17

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