1. Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.
- Author
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Babri S, Doosti MH, and Salari AA
- Subjects
- Animals, Animals, Newborn, Anxiety pathology, Body Weight drug effects, Corticosterone metabolism, Cytokines metabolism, Dark Adaptation drug effects, Depression pathology, Disease Models, Animal, Dose-Response Relationship, Drug, Exploratory Behavior drug effects, Female, Hindlimb Suspension methods, Immobility Response, Tonic drug effects, Male, Mice, Swimming psychology, Tumor Necrosis Factor-alpha drug effects, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha pharmacology, Anxiety chemically induced, Brain drug effects, Brain growth & development, Brain metabolism, Depression chemically induced, Sex Characteristics
- Abstract
A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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