Early life stress from allergic dermatitis causes depressive-like behaviors in adolescent male mice through neuroinflammatory priming
Open accessAbstract
Allergic dermatitis (AD), associated with pruritus and itchiness, is one of the major stressful conditions early in life. AD also influences the incidence of neuropsychiatric disorders and developmental disorders through neuro-immune interactions. To the best of our knowledge, there is no report that assesses the effects of early childhood dermatitis on psychiatric disorders later in life using an animal model. Here, we developed an oxazolone (Ox)-induced AD model in the early life of male C57BL/6J mice whose ears were challenged by Ox repeatedly from postnatal days (PD) 2 to PD30. On PD30, the Ox-treated ears were remarkably thickened and showed epidermal hyperplasia coupled with increased expression of T helper 2 cytokines, interleukin (IL)-4, and IL-13 in the ear tissue. Additionally, serum immunoglobulin E levels and serum corticosterone levels were higher in the Ox-treated mice than those in the control mice. Although Ox-treated PD40 mice showed neither behavioral abnormalities nor increases in pro-inflammatory cytokine expression in the brain, this study revealed that they experienced downregulation of CD200R1 expression in the amygdala under basal conditions and that additional lipopolysaccharide (LPS) administration induced enhanced neuroinflammatory reaction as the priming effect was accompanied by an increase of Iba-1-positive microglia in the amygdala and hippocampus. Furthermore, the Ox-treated PD40 mice showed depressive-like behaviors 24 h after LPS administration, whereas the control mice did not. Interestingly, the expression of indoleamine 2,3-dioxygenase and kynurenine 3-monooxygenase, key rate-limiting enzymes of the kynurenine metabolism pathway, was upregulated in the hippocampus, prefrontal cortex, and amygdala of the Ox-treated mice 4 h after LPS administration. Based on these results, we suggest that early life stress from AD aggravates susceptibility to systemic inflammation in the adolescent brain, leading to depressive behaviors with abnormal kynurenine metabolism.
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Early life stress has been linked to systemic inflammation, and this can increase the risk for depression.
“Various determinants, such as early life stress, have also been linked to systemic inflammation, and this can increase the risk for depression [186].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [186]
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- Authors
- Hashimoto, O., Kuniishi, H., Nakatake, Y., Yamada, M., Wada, K., & Sekiguchi, M.
- Affiliations
- National Center of Neurology and Psychiatry (JP)
- Tokyo University of Science (JP)
- Corresponding author
- Hashimoto, Okito
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 90
- Pages
- 319-331
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W3087428371
- Cited by
- 17
- References
- 88
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2022: 3 · 2021: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- allergic dermatitis, early life stress, depression-like behavior, neuroinflammation, neuroimmune interactions, oxazolone-induced dermatitis, CD200R1, amygdala, hippocampus, microglia, lipopolysaccharide, kynurenine metabolism, indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase, Th2 cytokines, immunoglobulin E, corticosterone, adolescent brain development
- MeSH terms
- Adverse Childhood Experiences, Animals, Child, Child, Preschool, Depression, Dermatitis, Hippocampus, Humans, Kynurenine, Lipopolysaccharides, Male, Mice, Inbred C57BL, Cytokines, Mice
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