2. Academic Validation
  3. HMGB1/RAGE signaling mediates the activation of microglia and participates in depressive-like behaviors and cognitive deficits in rats after ischemia-reperfusion

HMGB1/RAGE signaling mediates the activation of microglia and participates in depressive-like behaviors and cognitive deficits in rats after ischemia-reperfusion

  • Behav Brain Res. 2025 Aug 24:492:115662. doi: 10.1016/j.bbr.2025.115662.
Lifei Fan 1,  Xinyue Zhang 2,  Xiaojia Song 2,  Lina Yang 3,  Huanhuan Liu 2,  Yunfei Zhang 1,  Kun Li 1,  Xuejiao Jin 2,  Hao Lei 2,  Zhaohui Zhang 4,  Fuping Zhang 5,  Jinggui Song 6
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Xinxiang Medical College, Xinxiang 453000, China; Henan Provincial Key Laboratory of Biological Psychiatry (Xinxiang Medical College), Xinxiang 453000, China.
  • 2 The Second Affiliated Hospital of Xinxiang Medical College, Henan Provincial Psychiatric Hospital, Xinxiang 453000, China; Henan Provincial Key Laboratory of Biological Psychiatry (Xinxiang Medical College), Xinxiang 453000, China.
  • 3 The Second Affiliated Hospital of Xinxiang Medical College, Henan Provincial Psychiatric Hospital, Xinxiang 453000, China.
  • 4 The First Affiliated Hospital of Xinxiang Medical College, Xinxiang 453000, China.
  • 5 The Second Affiliated Hospital of Xinxiang Medical College, Henan Provincial Psychiatric Hospital, Xinxiang 453000, China; Henan Provincial Key Laboratory of Biological Psychiatry (Xinxiang Medical College), Xinxiang 453000, China. Electronic address: zhangfuping2141@163.com.
  • 6 The Second Affiliated Hospital of Xinxiang Medical College, Henan Provincial Psychiatric Hospital, Xinxiang 453000, China; Henan Provincial Key Laboratory of Biological Psychiatry (Xinxiang Medical College), Xinxiang 453000, China. Electronic address: songjg62@126.com.
PMID: 40419119 DOI: 10.1016/j.bbr.2025.115662
Abstract

Post-stroke depression (PSD) is a common psychiatric complication that occurs after stroke, especially in ischemic stroke (I/S). It has been reported that high-mobility group box-1 (HMGB1) is highly expressed in clinical PSD patients, but the exact molecular mechanism of its involvement in PSD is not completely clear, the neuroinflammation may participate in its development. Thus, we established a PSD rat model, observed behavioral and cognitive deficits, and found that the HMGB1/ receptor for advanced glycation end products (RAGE) pathway were activated in microglia. Glycyrrhizin acid (GA), an inhibitor of HMGB1, inhibited microglial activation, reversed the expression of HMGB1/RAGE, and ameliorated depressive-like behaviors in PSD rats. GA also reduced the expression of MAPK and NF-κB, which further led to decreased expression of IL-1β and NLRP3 inflammasome. These results suggested that the HMGB1/RAGE pathway was involved in microglial activation in the PSD model, promoting neuroinflammation and depressive-like behaviors.

Keywords

GA; HMGB1; Microglia; Neuroinflammation; PSD; RAGE.

Figures
Products