期刊
PSYCHOPHARMACOLOGY
卷 236, 期 10, 页码 2959-2973出版社
SPRINGER
DOI: 10.1007/s00213-019-5186-7
关键词
3 '-deoxyadenosine; Anxiolytic effect; Neuroimmune; Cytokines; Interleukin-4
资金
- National Natural Science Foundation of China [31560274, 31650005, 81760651]
- Yunnan Province Funding [KC1710123]
- Yunnan High-level Professional Funding [2012HA004]
- Department of Science and Technology of Yunnan Province
Rationale Converging evidence suggests that neuroimmunity plays an important role in the pathophysiology of anxiety. Interleukin (IL)-4 is a key cytokine regulating neuroimmune functions in the central nervous system. More efficient anxiolytics with neuro-immune mechanisms are urgently needed. Objective To determine whether 3'-deoxyadenosine (3'-dA) exerts an anxiolytic effect and to examine the role of IL-4 in the anxiolytic effect of 3'-dA in mice. Methods We investigated the effects of 3'-dA on anxiety-like behaviors using elevated plus maze (EPM) or light-dark box (LDB) tests after 45 min or 5 days of treatment. Expression of IL-4, IL-10, IL-1 beta, TNF-alpha, and IL-6 in the prefrontal cortex (PFC) was detected by Western blot and/or double immunostaining. Intracerebroventricular injection of RIL-4R alpha (an IL-4-specific inhibitor) and intraperitoneal injection of 3'-dA or imipramine were co-administered, followed by EPM test. Results 3'-dA exhibited a stronger and faster anxiolytic effect than imipramine in behavioral tests. Furthermore, 3'-dA enhanced IL-4 expression after 45 min or 5 days, TNF-alpha and IL-1 beta expression decreased significantly after a 5-day treatment with 3'-dA, and IL-10 expression increased after a 5-day treatment with 3'-dA or imipramine in the PFC. IL-4 was expressed in neurons and in some astrocytes and microglia. IL-4 expression showed a strong positive correlation with reduced anxiety behaviors. RIL-4R alpha completely blocked the anxiolytic effects induced by 3'-dA and imipramine. Conclusions This study identifies a novel and common anxiolytic IL-4 signaling pathway and provides an innovative drug with a novel neuro-immune mechanism for treating anxiety disorder.
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