ArticleJournal of neuroinflammation2022
Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Consideration of sex as a biological variable over the history of the 5xFAD Alzheimer's Disease mouse model.Biology of sex differences · 2025Article
- Chronic social isolation-unpredictable stress induces early-onset cognitive deficits and exacerbates Aβ accumulation in the 5xFAD mouse model of Alzheimer's disease.Molecular psychiatry · 2025Article
- Chloride Homeostasis in Neuronal Disorders: Bridging Measurement to Therapy.Life (Basel, Switzerland) · 2025Review
- Human milk-derived extracellular vesicles promote the heat shock response in polarized microglia.Cell stress & chaperones · 2025Article
- Nutritional interventions to counteract the detrimental consequences of early-life stress.Molecular psychiatry · 2025Review
- SARS-CoV-2 post-acute sequelae linked to inflammation via extracellular vesicles.Frontiers in immunology · 2025Article
- Sex-specific fear acquisition following early life stress is linked to amygdala and hippocampal purine and glutamate metabolism.Communications biology · 2024Article
- Developmental functions of microglia: Impact of psychosocial and physiological early life stress.Neuropharmacology · 2024Review
- Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice.Neurobiology of stress · 2024Article
- The neural basis of neuropsychiatric symptoms in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Maternal separation differentially modulates early pathology by sex in 5xFAD Alzheimer's disease-transgenic mice.Brain, behavior, & immunity - health · 2023Article
- Role of TET1-mediated epigenetic modulation in Alzheimer's disease.Neurobiology of disease · 2023Article
- Life Experience Matters: Enrichment and Stress Can Influence the Likelihood of Developing Alzheimer's Disease via Gut Microbiome.Biomedicines · 2023Review
- Article
- Sex-specific behavioral outcomes of early-life adversity and emerging microglia-dependent mechanisms.Frontiers in behavioral neuroscience · 2022Article
- Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe risk of developing Alzheimer's disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD.
methodsHere, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS.
resultsWe detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found altered Bdnf and Arc expression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure.
conclusionOverall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.