ArticleMolecular neurodegeneration2016
Early-life stress leads to impaired spatial learning and memory in middle-aged ApoE4-TR mice.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Early-Life Psychological Stress Impairs Spatial Learning and Memory in Rats by Altering the Hippocampal Proteome.Behavior genetics · 2026Article
- APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.Cell death & disease · 2026Article
- Article
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- Protective Potential ofCurrent issues in molecular biology · 2025Review
- Sex differences in cognition, anxiety-phenotype and therapeutic effect of metformin in the aged apoE-TR mice.Biology of sex differences · 2025Article
- S-ketamine alleviates depression-like behavior and hippocampal neuroplasticity in the offspring of mice that experience prenatal stress.Scientific reports · 2024Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- A Moderate Duration of Stress Promotes Behavioral Adaptation and Spatial Memory in Young C57BL/6J Mice.Brain sciences · 2022Article
- Ginsenoside Rh2 administration produces crucial antidepressant-like effects in a CUMS-induced mice model of depression.Brain and behavior · 2022Article
- Effect of metal ions on Alzheimer's disease.Brain and behavior · 2022Review
- KangPiLao decoction modulates cognitive and emotional disorders in rats with central fatigue through the GABA/Glu pathway.Frontiers in pharmacology · 2022Article
- Network and Experimental Pharmacology to Decode the Action of Wendan Decoction Against Generalized Anxiety Disorder.Drug design, development and therapy · 2022Article
- APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline.Translational psychiatry · 2021Article
- Hippocampal Glycerol-3-Phosphate Acyltransferases 4 and BDNF in the Progress of Obesity-Induced Depression.Frontiers in endocrinology · 2021Article
- Microglia, Lifestyle Stress, and Neurodegeneration.Immunity · 2020Review
- Corticotrophin releasing factor receptor 1 antagonists prevent chronic stress-induced behavioral changes and synapse loss in aged rats.Psychoneuroendocrinology · 2018Article
- Inhibiting RIP1 Improves Chronic Stress-Induced Cognitive Impairments in D-Galactose-Induced Aging Mice.Frontiers in behavioral neuroscience · 2018Article
- ApoE4-associated phospholipid dysregulation contributes to development of Tau hyper-phosphorylation after traumatic brain injury.Scientific reports · 2017Article
- Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism.Alzheimer's research & therapy · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApolipoprotein 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.
resultsAll 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.
conclusionThese 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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