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Local Interleukin-18 System in the Basolateral Amygdala Regulates Susceptibility to Chronic Stress

Title
Local Interleukin-18 System in the Basolateral Amygdala Regulates Susceptibility to Chronic Stress
Authors
Kim, Tae-KyungKim, Ji-EunChoi, JuliPark, Jin-YoungLee, Jung-EunLee, Eun-HwaLee, YunjinKim, Bo YeonOh, Young J.Han, Pyung-Lim
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2017
Journal Title
MOLECULAR NEUROBIOLOGY
ISSN
0893-7648JCR Link1559-1182JCR Link
Citation
vol. 54, no. 7, pp. 5347 - 5358
Keywords
Interleukin-18Chronic stressDepressionBLA
Publisher
HUMANA PRESS INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
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-1 alpha 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.
DOI
10.1007/s12035-016-0052-7
Appears in Collections:
일반대학원 > 뇌·인지과학과 > Journal papers
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