MiR-181c-5p ameliorates learning and memory in sleep-deprived mice via HMGB1/TLR4/NF-κB pathway

Area of Science:

• Neuroscience
• Molecular Biology
• Immunology

Background:

• Sleep deprivation (SD) induces cognitive impairment through neuroinflammation.
• The microRNA miR-181c-5p and High Mobility Group Box 1 (HMGB1) axis are implicated in anti-inflammatory processes.
• The precise mechanism by which miR-181c-5p enhances learning and memory in SD conditions is not fully understood.

Purpose of the Study:

• To investigate the role of miR-181c-5p in mitigating learning and memory deficits caused by sleep deprivation.
• To elucidate the molecular pathways involved in miR-181c-5p-mediated neuroprotection.

Main Methods:

• Overexpression of miR-181c-5p in the hippocampus of mice using lentivirus vector-miR-181c-5p (LV-miR-181c-5p) particles.
• Comparison of learning and memory performance, neuroinflammation markers (IBA-1), and key pathway proteins (HMGB1, TLR4, p-NF-κB) across four groups: control, SD, SD + miR-181c-5p, and SD + vector.

Main Results:

• Mice with overexpressed miR-181c-5p exhibited improved learning and memory compared to control vector-treated mice.
• Reduced levels of ionized calcium binding adaptor molecule 1 (IBA-1), a marker of neuroinflammation, were observed in the miR-181c-5p overexpressing group.
• Significant downregulation of HMGB1, TLR4, and phosphorylated NF-κB (p-NF-κB) expression in the hippocampus was noted.

Conclusions:

• miR-181c-5p effectively ameliorates learning and memory impairments induced by sleep deprivation in mice.
• The protective effect is mediated through the inhibition of the HMGB1/TLR4/NF-κB signaling pathway, thereby reducing neuroinflammation.