Authors
Hongguo Li, Siqi Song, Dongmei Tang, Yuchen Zhu, Xiping Zhang, Chaojie Wang, Yao Zhang, Mengxiao Du, Chenxu Liu, Yushi Hu
Published in
Neuroscience and biobehavioral reviews. Pages 106847. Jul 04, 2026. Epub Jul 04, 2026.
Abstract
Anxiety-related disorders are highly prevalent and persistently difficult to treat, largely due to insufficient understanding of peripheral-central regulatory mechanisms governing emotional behaviors. Irisin, an exercise-dependent myokine, serves as a critical peripheral-to-central signaling mediator modulating brain function and anxiety-like behavioral phenotypes. This review systematically integrates current preclinical evidence illustrating how irisin regulates anxiety through multi-level neural mechanisms. Irisin suppresses microglial NF-κB/STAT3-mediated neuroinflammation, enhances prefrontal-hippocampal synaptic plasticity via BDNF upregulation and AMPK/mTOR-related autophagy, and improves gut-brain axis homeostasis by stabilizing intestinal barrier integrity and reshaping microbial composition. Crucially, we propose a context-dependent therapeutic window model to reconcile contradictory pro-anxiogenic and anxiolytic findings across stress severity and pathological stages, resolving existing controversies in this field. We further summarize key unresolved limitations, including ambiguous central receptor identity, peripheral-central dissociation and sex-dependent heterogeneity. This work provides an integrated mechanistic framework linking muscular metabolic signals to affective circuit regulation, offering novel translational perspectives for anxiety behavioral modulation and targeted therapeutic development.
PMID:
42401319
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.
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