Babri Shirin, Doosti Mohammad-Hossein, Salari Ali-Akbar
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.
Behav Brain Res. 2014 Mar 15;261:305-14. doi: 10.1016/j.bbr.2013.12.037. Epub 2014 Jan 5.
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.
新出现的文献表明，新生儿感染是大脑、行为以及下丘脑-垂体-肾上腺轴发育的一个风险因素，这可能会影响其成年后的焦虑和抑郁相关行为。据记载，新生儿感染会提高新生啮齿动物体内肿瘤坏死因子-α（TNF-α）的浓度，并且这种感染可能至少部分地通过促炎细胞因子导致新生儿脑损伤。此外，先前的研究表明，TNF-α参与中枢神经系统发育过程中的细胞分化、神经发生和程序性细胞死亡。我们首次研究了新生儿期接触TNF-α是否会影响成年小鼠的体重、应激诱导的皮质酮（COR）、焦虑和抑郁相关行为。在本研究中，在出生后第3天和第5天给新生小鼠注射重组小鼠TNF-α（0.2、0.4、0.7和1μg/kg）或生理盐水，然后对成年雄性和雌性小鼠进行不同的行为测试。结果表明，新生儿期TNF-α处理会降低两性新生儿期的体重。此外，本研究结果表明，高剂量的TNF-α会增加成年雄性小鼠应激诱导的COR水平、焦虑和抑郁相关行为，但会增加成年雌性小鼠的焦虑水平，而对抑郁没有显著影响[已修正]。我们的研究结果表明，新生儿期接触TNF-α会以剂量和性别依赖的方式改变小鼠的大脑和行为发育。
