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The SIRT1-HMGB1 pathway in hippocampal microglia is involved in chronic heroin-induced cognitive impairment

Chunlu Li1, Yvjie Wei2, Dan Yin1

  • 1Department of Histology and Embryology, School of Basic Medical Sciences, Guizhou Medical University, Gui'an New District, 561113, Guizhou, China; Key Laboratory for Research on Autoimmune Diseases of Higher Education schools in Guizhou Province, Guiyang, China.

Pharmacology, Biochemistry, and Behavior
|January 23, 2026
PubMed

Insights

Chronic heroin use impairs learning and memory by activating the SIRT1-HMGB1 pathway in microglia, leading to hippocampal damage. This pathway contributes to cognitive deficits and inflammation in the brain.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Chronic heroin treatment is linked to cognitive impairment.
  • Microglia-mediated hippocampal damage is a potential mechanism.
  • The specific molecular pathways involved remain unclear.

Purpose of the Study:

  • To investigate the role of the SIRT1-HMGB1 pathway in heroin-induced cognitive impairment.
  • To explore the involvement of microglia and their polarization.

Main Methods:

  • Mice were subjected to chronic heroin treatment for 15 and 30 days.
  • Learning and memory were assessed using the water maze task.
  • Hippocampal expression of SIRT1 and HMGB1, microglial polarization, and cell apoptosis were analyzed.
  • Selective knockdown of SIRT1 in hippocampal microglia was performed.

Main Results:

  • 30 days of heroin treatment, but not 15 days, impaired learning and memory.
  • Longer heroin exposure increased hippocampal SIRT1 and HMGB1 expression, particularly in microglia.
  • Heroin treatment promoted proinflammatory microglial polarization and exacerbated hippocampal cell apoptosis.
  • SIRT1 knockdown worsened cognitive deficits and apoptosis while reducing HMGB1-positive microglia.

Conclusions:

  • Chronic heroin treatment impairs cognitive function by activating the SIRT1-HMGB1 pathway in microglia.
  • This activation promotes neuroinflammation and cell apoptosis in the hippocampus.
  • The SIRT1-HMGB1 pathway in microglia is a key player in heroin-induced cognitive impairment.
Keywords:
Chronic heroin treatmentCognitive impairmentMicrogliaSIRT1-HMGB1hippocampus

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