期刊
ENEURO
卷 4, 期 6, 页码 -出版社
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0147-17.2017
关键词
anxiety; astrocytes; cytokines; IL-33; oligodendrocytes; social behavior
资金
- National Institute of Mental Health [R00 MH093458]
- Johns Hopkins Medicine Discovery Fund
- National Institute of Health [S10OD016374]
Interleukin (IL)-33 is a member of the IL-1 family of cytokines. IL-33 is expressed in nuclei and secreted as alarmin upon cellular damage to deliver a danger signal to the surrounding cells. Previous studies showed that IL-33 is expressed in the brain and that it is involved in neuroinflammatory and neurodegenerative processes in both humans and rodents. Nevertheless, the role of IL-33 in physiological brain function and behavior remains unclear. Here, we have investigated the behaviors of mice lacking IL-33 (Il33(-/-) mice). IL-33 is constitutively expressed throughout the adult mouse brain, mainly in oligodendrocyte-lineage cells and astrocytes. Notably, Il33(-/-) mice exhibited reduced anxiety-like behaviors in the elevated plus maze (EPM) and the open field test (OFT), as well as deficits in social novelty recognition, despite their intact sociability, in the three-chamber social interaction test. The immunoreactivity of c-Fos proteins, an indicator of neuronal activity, was altered in several brain regions implicated in anxiety-related behaviors, such as the medial prefrontal cortex (mPFC), amygdala, and piriform cortex (PCX), in Il33(-/-) mice after the EPM. Altered c-Fos immunoreactivity in Il33(-/-) mice was not correlated with IL-33 expression in wild-type (WT) mice nor was IL-33 expression affected by the EPM in WT mice. Thus, our study has revealed that Il33(-/-) mice exhibit multiple behavioral deficits, such as reduced anxiety and impaired social recognition. Our findings also indicate that IL-33 may regulate the development and/or maturation of neuronal circuits, rather than control neuronal activities in adult brains.
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