Nowacka-Chmielewska Marta M, Kasprowska Daniela, Paul-Samojedny Monika, Bielecka-Wajdman Anna M, Barski Jarosław J, Małecki Andrzej, Obuchowicz Ewa
Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland; Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland.
Pharmacol Rep. 2017 Jun;69(3):520-525. doi: 10.1016/j.pharep.2017.01.004. Epub 2017 Jan 17.
Stress is a major predisposing factor in the development of psychiatric disorders and potential source of augmented inflammatory processes in the brain. Increasing body of evidence shows an important role of alterations in the olfactory bulbs (OBs) function in stress-related disorders. The aim of the present study was to investigate the impact of antidepressants on the alterations of brain-derived neurotrophic factor (BDNF) induced by lipopolysaccharide (LPS) in female rats subjected to chronic social instability stress (CSIS).
9 weeks old female rats were subjected to CSIS and injected ip once daily with desipramine (10mg/kg), fluoxetine (5mg/kg), or tianeptine (10mg/kg) for 4 weeks. On the last day of the experiment, rats being at the estrus phase of cycle were injected ip with LPS (1mg/kg) or saline.
The BDNF mRNA and protein levels were evaluated in the olfactory bulbs. and the BDNF protein levels were measured in plasma. A single LPS administration in the stressed rats resulted in significant decrease in the bulbar BDNF mRNA, but not in the protein level. Chronic administration of desipramine, fluoxetine, or tianeptine increased the BDNF mRNA expression and protein levels in the LPS-injected stressed rats. There was no effect of the studied antidepressants on the reduction of the plasma BDNF protein level induced by CSIS and LPS.
These results suggest that studied antidepressants were effective in inhibiting the impact of LPS on BDNF expression in the stressed rats what may be significant for beneficial action of this drugs.
应激是精神疾病发生的主要诱发因素,也是大脑炎症过程增强的潜在来源。越来越多的证据表明嗅球(OBs)功能改变在应激相关疾病中起重要作用。本研究的目的是调查抗抑郁药对遭受慢性社会不稳定应激(CSIS)的雌性大鼠中脂多糖(LPS)诱导的脑源性神经营养因子(BDNF)改变的影响。
9周龄雌性大鼠接受CSIS处理,并每天一次腹腔注射去甲丙咪嗪(10mg/kg)、氟西汀(5mg/kg)或噻奈普汀(10mg/kg),持续4周。在实验的最后一天,处于发情周期阶段的大鼠腹腔注射LPS(1mg/kg)或生理盐水。
在嗅球中评估BDNF mRNA和蛋白水平,并在血浆中测量BDNF蛋白水平。在应激大鼠中单次注射LPS导致嗅球BDNF mRNA显著降低,但蛋白水平未降低。慢性给予去甲丙咪嗪、氟西汀或噻奈普汀可增加注射LPS的应激大鼠中BDNF mRNA表达和蛋白水平。所研究的抗抑郁药对CSIS和LPS诱导的血浆BDNF蛋白水平降低没有影响。
这些结果表明,所研究的抗抑郁药可有效抑制LPS对应激大鼠BDNF表达的影响,这可能对这些药物的有益作用具有重要意义。