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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2016

Open Access 01-12-2016 | Research article

Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice

Authors: Lan-yan Lin, Jing Zhang, Xiao-man Dai, Nai-an Xiao, Xi-lin Wu, Zhen Wei, Wen-ting Fang, Yuan-gui Zhu, Xiao-chun Chen

Published in: Molecular Neurodegeneration | Issue 1/2016

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Abstract

Background

Apolipoprotein E (ApoE) is a major lipid carrier that supports lipid transport and injury repair in the brain. The APOE ε4 allele is associated with depression, mild cognitive impairment (MCI) and dementia; however, the precise molecular mechanism through which ApoE4 influences the risk of disease development remains unknown. To address this gap in knowledge, we investigated the potential effects of chronic unpredictable mild stress (CUMS) on ApoE3 and ApoE4 target replacement (ApoE3-TR and ApoE4-TR) mice.

Results

All ApoE-TR mice exposed to CUMS at 3 months old recovered from a depression-like state by the age of 12 months. Of note, ApoE4-TR mice, unlike age-matched ApoE3-TR mice, displayed impaired spatial cognitive abilities, loss of GABAergic neurons, decreased expression of Reelin, PSD95, SYN and Fyn, and reduced phosphorylation of NMDAR2B and CREB.

Conclusion

These results suggest that early-life stress may mediate cognitive impairment in middle-age ApoE4-TR mice through sustained reduction of GABAergic neurons and Reelin expression, which might further diminish the activation of the Fyn/NMDAR2B signaling pathway.
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Metadata
Title
Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice
Authors
Lan-yan Lin
Jing Zhang
Xiao-man Dai
Nai-an Xiao
Xi-lin Wu
Zhen Wei
Wen-ting Fang
Yuan-gui Zhu
Xiao-chun Chen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2016
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-016-0107-2

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