Obuchowicz Ewa, Nowacka Marta, Paul-Samojedny Monika, Bielecka-Wajdman Anna M, Małecki Andrzej
Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, 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; Center for Experimental Medicine, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Cytokine. 2017 Feb;90:6-13. doi: 10.1016/j.cyto.2016.10.001. Epub 2016 Oct 12.
The present study was designed to evaluate, for the first time, the potential sex differences in BDNF and VEGF systems under normal conditions and in response to IL-1β given ip. Peripheral overproduction of this cytokine mediates the pathophysiology of various acute neuroinflammatory states. Until now, the effect of IL-1β on VEGF expression in rat brain structures and its serum level has not been examined. In male and female rats, the BDNF and VEGF mRNA expression, and BDNF level were evaluated in the amygdala, hippocampus, hypothalamus and pituitary gland. The VEGF levels were determined in the pituitary. Serum BDNF and VEGF levels were also measured. The pituitary BDNF mRNA, and BDNF and VEGF levels were higher in females than in male rats whereas in males, the BDNF levels were higher in the other brain structures. The serum BDNF concentration was similar in both groups but VEGF levels were enhanced in females. Following IL-1β (50μg/kg ip.) administration, a higher serum IL-1β level was detected in females than in males. In male rats, IL-1β decreased BDNF mRNA in all the brain structures, except for the pituitary, and VEGF mRNA in the amygdala. In opposite, IL-1β challenge in females increased the pituitary VEGF mRNA and serum BDNF and VEGF levels. These results suggest that in females BDNF and VEGF may play a more important role in the pituitary function. In males, amygdala trophic system seems to be especially sensitive to the enhanced peripheral IL-1β production. Our findings point to the need to consider sex-related differences to be able to draw reliable conclusions about changes in BDNF and VEGF levels during inflammation.
本研究旨在首次评估正常条件下以及腹腔注射白细胞介素-1β后，脑源性神经营养因子（BDNF）和血管内皮生长因子（VEGF）系统中潜在的性别差异。这种细胞因子的外周过量产生介导了各种急性神经炎症状态的病理生理学过程。到目前为止，白细胞介素-1β对大鼠脑结构中VEGF表达及其血清水平的影响尚未得到研究。在雄性和雌性大鼠中，评估了杏仁核、海马体、下丘脑和垂体中BDNF和VEGF mRNA的表达以及BDNF水平。测定了垂体中的VEGF水平。还测量了血清BDNF和VEGF水平。雌性大鼠垂体中的BDNF mRNA、BDNF和VEGF水平高于雄性大鼠，而在雄性大鼠中，其他脑结构中的BDNF水平较高。两组的血清BDNF浓度相似，但雌性大鼠的VEGF水平升高。腹腔注射白细胞介素-1β（50μg/kg）后，检测到雌性大鼠的血清白细胞介素-1β水平高于雄性大鼠。在雄性大鼠中，白细胞介素-1β降低了除垂体外所有脑结构中的BDNF mRNA以及杏仁核中的VEGF mRNA。相反，雌性大鼠接受白细胞介素-1β刺激后，垂体VEGF mRNA以及血清BDNF和VEGF水平升高。这些结果表明，BDNF和VEGF在雌性大鼠的垂体功能中可能发挥更重要的作用。在雄性大鼠中，杏仁核营养系统似乎对外周白细胞介素-1β产生的增加特别敏感。我们的研究结果表明，需要考虑性别相关差异，以便能够就炎症期间BDNF和VEGF水平的变化得出可靠的结论。
