🧬 BDNF Extraction Viewer

Chronic psychological stress drives neuroimmune crosstalk and accelerates atherosclerosis progression. Physical exercise confers broad health benefits and is associated with reduced inflammation. However, the exercise-mediated factors and mechanisms that mitigate stress-induced vascular inflammation remain unclear. Chronic restraint stress (CRS) and voluntary exercise models were established to investigate the role of exercise in neuroimmune crosstalk. RNA sequencing identified kinesin family member 4 (Kif4) as a key gene associated with the attenuation of stress-induced inflammatory responses in peripheral blood monocytes following exercise. Combined co-immunoprecipitation-mass spectrometry and membrane proteomics identified T cell-interacting activating receptors on myeloid cell 1 (TARM1) as the Kif4 cargo. The function of TARM1 was validated using an immobilized TARM1-Fc fusion protein. Brain-derived neurotrophic factor (BDNF), a key effector during exercise and stress, regulated the Kif4-TARM1 axis using recombinant BDNF (rBDNF) and the TrkB inhibitor ANA-12. Finally, exercise-mediated effects and mechanisms were examined in atherosclerotic CRS-exposed mouse models and in patients with coronary artery disease (CAD) experiencing high psychological stress. Physical exercise alleviated stress-induced neuroimmune crosstalk, reduced the proinflammatory CD11b Physical exercise alleviates stress-induced neuroimmune crosstalk through the BDNF-Kif4-TARM1 axis, revealing a novel neuroimmune-mediated brain-heart axis that supports exercise-based therapeutic strategies for psychogenic CAD. Chronic psychological stress drives systemic inflammation through neuroimmune mechanisms, thereby accelerating the progression of coronary artery disease (CAD). Physical exercise alleviates stress-induced neuroimmune crosstalk, partly by suppressing proinflammatory responses in monocytes/macrophages. This study provides novel insights into exercise-regulated neuroimmune mechanisms involving the monocyte BDNF-Kif4-TARM1 axis. In both an atherosclerotic mouse model and patients with CAD, exercise mitigated stress-induced inflammation via the BDNF-Kif4-TARM1 axis.