title: Tumor necrosis factor-alpha during neonatal brain development affects anxiety- and depression-related behaviors in adult male and female mice.
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.
authors.affiliation: Laboratory of Physiology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Babri
authors.affiliation: Laboratory of Immunology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad-Hossein
authors.initials: MH
authors.lastname: Doosti
authors.affiliation: Laboratory of Physiology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Laboratory of Immunology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: aa.salari@yahoo.com.
authors.forename: Ali-Akbar
authors.initials: AA
authors.lastname: Salari
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003623:Dark Adaptation / Q000187:drug effects; D003863:Depression / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D019417:Hindlimb Suspension / Q000379:methods; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D051379:Mice; D012727:Sex Characteristics; D013550:Swimming / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone
keywords: Anxiety; Cytokines; Depression; Early life stress; HPA axis; Neonatal infection; TNF-α