title: Local Interleukin-18 System in the Basolateral Amygdala Regulates Susceptibility to Chronic Stress.
abstract: Interleukin-18 (IL18) is a multifunctional cytokine that has been implicated in increased susceptibility to depression; however, the underlying mechanism remains unknown. We found that the IL18 system in the basolateral amygdala (BLA) determined susceptibility to chronic stress. Mice subjected to chronic restraint stress or chronic foot-shock stress demonstrated increased expression of IL18 in the BLA, and exhibited depression-like behaviors, whereas IL18 knockout (KO) mice were resilient to these chronic stresses. IL18 and IL18 receptors in the BLA were expressed in glutamatergic and GABAergic neurons in addition to glial cells. Local inhibition of IL18 and IL18 receptors in the BLA by stereotaxic injection of siRNA-IL18 or siRNA-IL18 receptor-1α was sufficient to suppress stress-induced depression-like behaviors. Following chronic stress, the downstream mediator of IL18 receptor activation, phospho-NF-kB, was increased in BLA neurons expressing IL18 receptors. Furthermore, siRNA-mediated inhibition of NF-kB in the BLA significantly suppressed stress-induced depression-like behaviors, and NF-kB KO mice were resilient to chronic stress. The siRNA-mediated inhibition of NF-kB in the BLA downregulated stress-induced increased expression of Hcrt, MCH, OXT, AVP, and TRH, the neuropeptides that were induced by chronic stress in the BLA and promoted depression-like behaviors. These results suggest that the local IL18 and its receptor system in the BLA function as molecular regulators promoting susceptibility to chronic stress.
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors: Tae-Kyung
authors: TK
authors: Kim
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors: Ji-Eun
authors: JE
authors: Kim
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors: Juli
authors: J
authors: Choi
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors: Jin-Young
authors: JY
authors: Park
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors: Jung-Eun
authors: JE
authors: Lee
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors: Eun-Hwa
authors: EH
authors: Lee
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
authors: Yunjin
authors: Y
authors: Lee
authors: World Class Institute, Korea Research Institute of Bioscience & Biotechnology, Science Park, Cheongwon, 363-883, South Korea.
authors: Bo Yeon
authors: BY
authors: Kim
authors: Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul, 120-749, South Korea. yjoh@yonsei.ac.kr.
authors: Young J
authors: YJ
authors: Oh
authors: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea. plhan@ewha.ac.kr.|Chemistry and Nano Science, Ewha Womans University, Seoul, Republic of Korea. plhan@ewha.ac.kr.
authors: Pyung-Lim
authors: PL
authors: Han
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D066272:Basolateral Nuclear Complex / Q000378:metabolism*; D003863:Depression / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012149:Restraint, Physical / Q000379:methods; D013312:Stress, Physiological; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D020382:Interleukin-18
keywords: BLA; Chronic stress; Depression; Interleukin-18