Sex differences in the effect of acute peripheral IL-1b administration on the brain and serum BDNF and VEGF expression in rats Ewa Obuchowicz a,⇑ , Marta Nowacka a,b,c , Monika Paul-Samojedny d , Anna M. Bielecka-Wajdman a , Andrzej Malecki b a Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland b Laboratory of Molecular Biology, Faculty of Physiotherapy, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland c Center for Experimental Medicine, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland d Department of Medical Genetics, Faculty of Pharmacy with Division of Laboratory Medicine, Sosnowiec, Medical University of Silesia in Katowice, Poland article info Article history: Received 12 April 2016 Received in revised form 7 September 2016 Accepted 3 October 2016 Keywords: BDNF VEGF IL-1b Male and female rats abstract 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-1b given ip. Peripheral overproduction of this cytokine mediates the pathophysiology of various acute neuroinflammatory states. Until now, the effect of IL-1b 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-1b (50 lg/kg ip.) administration, a higher serum IL-1b level was detected in females than in males. In male rats, IL-1b decreased BDNF mRNA in all the brain structures, except for the pituitary, and VEGF mRNA in the amygdala. In opposite, IL-1b 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-1b 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. Ó 2016 Elsevier Ltd. All rights reserved. 1. Introduction Sex differences in brain morphology and function and in hor- mone levels are believed to be the basis of differences in the preva- lence, symptoms and course of neuropsychiatric disorders between women and men. The key element undoubtedly determining the risk of development of affective diseases is the stress-coping system, in which the hypothalamic-pituitaryadrenal (HPA) axis plays an important role. In fact, females and males were reported to differ in the regulation of the stress response [1,2]. Moreover, the sexual dimorphism of immunity is also of significance since the interaction between the brain and the immune system contributes to pathophysiology of mental diseases [3]. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are representatives of neu- rotrophins. BDNF discovered by Barde et al. [4] is the most abundant trophic factor with widespread expression in the mammalian brain. Mature BDNF binds to TrkB receptors and stim- ulates downstream signaling pathways influencing such effects as neuronal differentiation, neurite outgrowth, increased cell survival and strengthening of synapse [5]. Due to its role in neurogenesis and long term potentiation, the BDNF signaling in the limbic struc- tures and cerebral cortex is essential for learning and memory [6]. http://dx.doi.org/10.1016/j.cyto.2016.10.001 1043-4666/Ó 2016 Elsevier Ltd. All rights reserved. Abbreviations: ACTH, adrenocorticotropin hormone; AVP, arginine vasopressin; BDNF, brain-derived neurotrophic factor; CORT, corticosterone; CNS, central nervous system; CRH, corticotropin-releasing hormone; CVOs, circumventricular organs; FS cells, folliculo–steallate cells; HPA axis, hypothalamic–pituitary–adrenal axis; LPS, lipopolysaccharide, OXT, oxytocin; PAC, peritoneal adherent cells; VEGF, vascular endothelial growth factor. ⇑ Corresponding author at: Department of Pharmacology, School of Medicine, Medyków 18 Street, 40-752 Katowice, Medical University of Silesia in Katowice, Poland. E-mail address: eobuchowicz@sum.edu.pl (E. Obuchowicz). Cytokine 90 (2017) 6–13 Contents lists available at ScienceDirect Cytokine journal homepage: www.journals.elsevier.com/cytokine