Interleukin-18 and its receptor are expressed in gonadotropin-releasing hormone neurons of mouse and rat forebrain

• Published in: Neuroscience letters 2017-05, Vol.650, p.33-37
• Main Authors: Kuwahara-Otani, Sachi, Maeda, Seishi, Kobayashi, Kimiko, Minato, Yusuke, Tanaka, Koichi, Yamanishi, Kyosuke, Hata, Masaki, Li, Wen, Hayakawa, Tetsu, Noguchi, Koichi, Okamura, Haruki, Yagi, Hideshi
• Format: Article
• Language: English
• Subjects: Animals; Gene Expression Regulation - physiology; GnRH neuron; Gonadotropin-Releasing Hormone - metabolism; Hypothalamus; Hypothalamus - metabolism; IL-18; IL-18Rα; Interleukin-18 - metabolism; Mice; Mice, Inbred C57BL; Neurons - cytology; Neurons - metabolism; Organ Specificity - physiology; Prosencephalon - cytology; Prosencephalon - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-18 - metabolism; Species Specificity; Tissue Distribution
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2017.03.051

•IL-18 and IL-18Rα are distributed within the basal forebrain in a continuum that extends from the medial septum through to the anterior hypothalamic area.•IL-18Rα is expressed in approximately 60% of GnRH neurons.•IL-18 is expressed in all GnRH neurons. Interleukin-18 (IL-18) is a pro-inflammatory cytokine and an important mediator of peripheral inflammation and host immune response. IL-18 functions through its binding with the IL-18 receptor (IL-18R), which consists of two chains, an IL-18-binding α chain (IL-18Rα) and a signaling β chain. IL-18 and IL-18R are expressed in the brain; however, limited information is available on IL-18R expression and the role of IL-18 in neurosecretory cells. In the present study, we used immunohistochemical techniques to investigate the distribution of IL-18Rα and IL-18 in the hypothalamus of male mice and rats. IL-18Rα-positive and IL-18-positive perikarya and fibers were found scattered throughout the medial septal nucleus, the nuclei of the vertical and horizontal limbs of the diagonal band, the organum vasculosum of the laminae terminalis, the preoptic area, and the anterior hypothalamic area. It is well known that gonadotropin-releasing hormone (GnRH) neuronal somata and/or fibers are found in these regions. Therefore, we performed double-label immunofluorescence for IL-18Rα/IL-18 and GnRH. IL-18Rα was expressed in approximately 60% of GnRH-immunopositive perikarya, and IL-18 was distributed in all GnRH-immunopositive perikarya. These observations suggest that IL-18 exerts direct effects upon the GnRH neuron via IL-18Rα and acts on GnRH neurons through an autocrine or paracrine pathway.