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丙咪嗪可逆转母婴分离诱导的成年大鼠细胞因子和 BDNF 水平的改变。

Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats.

机构信息

Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.

出版信息

Behav Brain Res. 2013 Apr 1;242:40-6. doi: 10.1016/j.bbr.2012.11.044. Epub 2012 Dec 10.

Abstract

A growing body of evidence is pointing toward an association between immune molecules, as well brain-derived neurotrophic factor (BDNF) and the depression. The present study was aimed to evaluate the behavioral and molecular effects of the antidepressant imipramine in maternally deprived adult rats. To this aim, maternally deprived and non-deprived (control group) male rats were treated with imipramine (30mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming test. In addition to this, IL-10, TNF-α and IL-1β cytokines were assessed in the serum and cerebrospinal fluid (CSF). In addition, BDNF protein levels were assessed in the prefrontal cortex, hippocampus and amygdala. In deprived rats treated with saline was observed an increase on immobility time, compared with non-deprived rats treated with imipramine (p<0.05). Deprived rats treated with saline presented a decrease on BDNF levels in the amygdala (p<0.05), compared with all other groups. The IL-10 levels were decreased in the serum (p<0.05). TNF-α and IL-1β levels were increased in the serum and CSF of deprived rats treated with saline (p<0.05). Interestingly, imipramine treatment reversed the effects of maternal deprivation on BDNF and cytokines levels (p<0.05). Finally, these findings further support a relationship between immune activation, neurotrophins and the depression, and considering the action of imipramine, it is suggested that classic antidepressants could exert their effects by modulating the immune system.

摘要

越来越多的证据表明,免疫分子与脑源性神经营养因子(BDNF)与抑郁症之间存在关联。本研究旨在评估抗抑郁药丙咪嗪对母婴分离成年大鼠的行为和分子影响。为此,对母婴分离和未分离(对照组)的雄性大鼠进行了为期 14 天的成年期丙咪嗪(30mg/kg)治疗。然后使用强迫游泳试验评估它们的行为。除此之外,还评估了血清和脑脊液(CSF)中的 IL-10、TNF-α 和 IL-1β 细胞因子。此外,还评估了前额叶皮质、海马体和杏仁核中的 BDNF 蛋白水平。与用丙咪嗪治疗的未分离大鼠相比,用生理盐水治疗的分离大鼠的不动时间增加(p<0.05)。与所有其他组相比,用生理盐水治疗的分离大鼠的杏仁核中的 BDNF 水平降低(p<0.05)。血清中的 IL-10 水平降低(p<0.05)。用生理盐水治疗的分离大鼠的血清和 CSF 中的 TNF-α 和 IL-1β 水平升高(p<0.05)。有趣的是,丙咪嗪治疗逆转了母婴分离对 BDNF 和细胞因子水平的影响(p<0.05)。最后,这些发现进一步支持了免疫激活、神经营养因子与抑郁症之间的关系,并且考虑到丙咪嗪的作用,提示经典抗抑郁药可能通过调节免疫系统发挥作用。

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