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Cited by 41Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeurological Disease Mechanisms and Treatments

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

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Lin, Lan-yan, Zhang, Jing, Dai, Xiao-man, Xiao, Nai-an, Wu, Xi-lin, Wei, Zhen, Fang, Wen-ting, Zhu, Yuan-gui +1 more·2016·Molecular Neurodegeneration
DOI 10.1186/s13024-016-0107-2PMC PMC4941053
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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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  • An early-life depression event elevates the subsequent AD risk.

    “An early-life depression event elevates the subsequent AD risk [34].”

    From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [34]

    The Background (page unavailable) says early-life depressive symptoms may increase the risk of cognitive impairment in old age. It does not establish that an early-life depressive episode increases subsequent Alzheimer’s disease risk; the AD-risk finding it discusses concerns late-onset depression together with APOE4. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Compared with apoE3 at 3 months of age, apoE4 did not aggravate depression-like behaviors under chronic unpredictable mild stress (CUMS).

    “Our previous research has shown that compared with apoE3 at the age of 3 months, apoE4 did not aggravate the depression-like behaviors under chronic unpredictable mild stress (CUMS) [34].”

    From APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline (2021) · cites this paper as [34]

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Cited by

Sorted by citations

Authors
Lin, L.-Y., Zhang, J., Dai, X.-M., Xiao, N.-A., Wu, X.-L., Wei, Z., Fang, W.-T., Zhu, Y.-G., & Chen, X.-C.
Affiliations
Fujian Medical University (CN)
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2016-07-12
Volume
11
Issue
1
Pages
51-51
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/s13024-016-0107-2
PMC
PMC4941053
OpenAlex
W2468956168
Cited by
41
References
6
Citations by year
2026: 7 · 2025: 8 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3
FWCI
1.83
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (91232709, 81171216, 81161120496, 81401149)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
early life stress, chronic unpredictable mild stress, APOE ε4, APOE3, spatial learning and memory, cognitive impairment, depression-like behavior, GABAergic neurons, reelin, PSD-95, synaptophysin, Fyn, NMDAR2B, CREB, middle age (human life stage)
MeSH terms
Reelin Protein, Aging, Animals, Dementia, Humans, Male, Memory, Mice, Transgenic, Neurons, Stress, Psychological, Mice, Apolipoprotein E4, Spatial Learning

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