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Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice
Abstract
Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early life inflammation in adulthood.
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“while minocycline treatment can rescue the effects of early life stress induced neuroinflammation during adulthood (Majidi et al., 2016).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Majidi et al., 2016
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Metadata
- Authors
- Majidi, J., Kosari-Nasab, M., & Salari, A.-A.
- Affiliations
- Tabriz University of Medical Sciences (IR)
- Corresponding author
- Salari, Ali-Akbar
- Venue
- Brain Research Bulletin
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 120
- Pages
- 1-13
- ISSN
- 0361-9230 (ISSN-L)
- OpenAlex
- W2190926078
- Cited by
- 109
- References
- 93
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 14 · 2020: 16 · 2019: 12 · 2018: 11 · 2017: 15 · 2016: 1
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Drug Applied Research Center at Tabriz University of Medical Sciences (GN-90-32)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- minocycline, lipopolysaccharide, anxiety-like behavior, depression-like behavior, HPA axis hyperactivity, hippocampal inflammation, microglial activation, early-life inflammation, stress response, corticosterone, TNF-α, IL-1β, neuroinflammation, antidepressant effects
- MeSH terms
- Animals, Animals, Newborn, Anti-Bacterial Agents, Anxiety Disorders, Depressive Disorder, Disease Models, Animal, Female, Hippocampus, Hypothalamo-Hypophyseal System, Inflammation, Lactation, Lipopolysaccharides, Male, Minocycline, Pituitary-Adrenal System, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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