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

Lookup NU author(s): Professor Tiago Outeiro

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Abstract

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-β 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-β 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. © 2012 Elsevier Inc.


Publication metadata

Author(s): Kemppainen S, Rantamaki T, Jeronimo-Santos A, Lavasseur G, Autio H, Karpova N, Karkkainen E, Staven S, Miranda HV, Outeiro TF, Diogenes MJ, Laroche S, Davis S, Sebastiao AM, Castren E, Tanila H

Publication type: Article

Publication status: Published

Journal: Neurobiology of Aging

Year: 2012

Volume: 33

Issue: 6

Pages: 1122.e23-1122.e39

Print publication date: 01/06/2012

Online publication date: 30/12/2011

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.neurobiolaging.2011.11.006

DOI: 10.1016/j.neurobiolaging.2011.11.006

PubMed id: 22209410


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