Cited by 109Stress Responses and CortisolTryptophan and brain disordersNeuroinflammation and Neurodegeneration Mechanisms

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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

Majidi, Jafar, Kosari-Nasab, Morteza, Salari, Ali-Akbar·2016·Brain Research Bulletin

DOI 10.1016/j.brainresbull.2015.10.009

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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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Authors: Majidi, J., Kosari-Nasab, M., & Salari, A.-A.
Affiliations: Tabriz University of Medical Sciences (IR)
Corresponding author: Salari, Ali-Akbar
ORCID: Majidi, Jafar
Salari, Ali-Akbar
Venue: Brain Research Bulletin
Publisher: Elsevier BV
Published: 2016-01
Volume: 120
Pages: 1-13
ISSN: 0361-9230 (ISSN-L)
DOI: 10.1016/j.brainresbull.2015.10.009
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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

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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

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