LEP Knockdown Improves Functional Recovery After Spinal Cord Injury and Potentially Regulates Microglial Polarization...

Area of Science:

• Neuroscience
• Immunology
• Regenerative Medicine

Background:

• Neuroinflammation, driven by microglial activation, impedes recovery after spinal cord injury (SCI).
• Leptin (LEP) is implicated in SCI pathogenesis, but its precise role in neuroinflammation and microglial response requires elucidation.

Purpose of the Study:

• To investigate the regulatory role of leptin (LEP) in spinal cord injury (SCI).
• To examine LEP's effects on the JAK-STAT signaling pathway, microglial polarization, and neuronal injury post-SCI.

Main Methods:

• Transcriptome sequencing identified differentially expressed genes and pathways in SCI.
• A mouse SCI model was used to assess functional recovery and pathology after LEP silencing via shRNA.
• Molecular techniques (qRT-PCR, Western blot, immunofluorescence) analyzed inflammatory mediators, microglial polarization, and JAK-STAT signaling.

Main Results:

• LEP knockdown significantly improved motor function recovery and reduced pathological damage after SCI.
• LEP silencing suppressed JAK-STAT pathway activation, shifted microglia from M1 to M2 phenotype, and reduced pro-inflammatory cytokines.
• LEP intervention attenuated neuronal apoptosis and oxidative stress, enhancing neuroprotection.

Conclusions:

• Leptin (LEP) acts as a key modulator in SCI-induced neuroinflammation, primarily through the JAK-STAT signaling pathway.
• Silencing LEP promotes M2 microglial polarization and reduces neuronal damage, ultimately enhancing spinal cord repair and functional recovery.
• Targeting LEP offers a promising therapeutic strategy for improving outcomes after spinal cord injury.