Sitagliptin improves functional recovery via GLP-1R-induced anti-apoptosis and facilitation of axonal regeneration after spinal cord injury

J Cell Mol Med, 2020 · DOI: 10.1111/jcmm.15501 · Published: August 1, 2020

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

This study investigates the potential of sitagliptin, a DPP-4 inhibitor, to promote recovery after spinal cord injury (SCI). The roles and the underlying mechanisms of sitagliptin in SCI repairing remain unclear. The research uses a rat model of SCI and explores the mechanisms underlying sitagliptin's effects on SCI recovery using PC12 cells and primary cortical neurons. In this study, we used a rat model of SCI and PC12 cells/primary cortical neurons to explore the mechanism of sitagliptin underlying SCI recovery. The study reveals that sitagliptin increases GLP-1R protein levels, reduces neuronal apoptosis, enhances axon regeneration, and improves functional recovery after SCI. Administration of sitagliptin significantly increased GLP-1R protein level, alleviated neuronal apoptosis, enhanced axon regeneration and improved functional recovery following SCI.

Study Duration

28 days

Participants

Adult female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Sitagliptin administration significantly increased GLP-1R protein level, alleviated neuronal apoptosis following SCI. Administration of sitagliptin significantly increased GLP-1R protein level, alleviated neuronal apoptosis
2
Sitagliptin enhances axon regeneration and improves functional recovery following SCI in rats. enhanced axon regeneration and improved functional recovery following SCI
3
The protective effect of sitagliptin can be reversed by treatment with exendin9-39, a GLP-1R inhibitor, remarkably reversed the protective effect of sitagliptin.

Research Summary

This study assesses the neuroprotective effects of sitagliptin and explores the possible underlying molecular mechanism of the neuroprotection of sitagliptin after SCI both in vivo and in vitro. It was discovered that sitagliptin attenuated neuronal apoptosis, improved microtubule stabilization as well as axon regeneration, and preserved neurological function by stimulating GLP-1R after SCI. We discovered that administration of sitagliptin attenuated neuronal apoptosis, improved microtubule stabilization as well as axon regeneration, and preserved neurological function by stimulating GLP-1R after SCI. The study indicates that the beneficial effects of GLP-1R stimulated by sitagliptin in SCI is involved in activating AMPK/ PGC-1α signalling pathway. Additionally, we point out that the beneficial effects of GLP-1R stimulated by sitagliptin in SCI is involved in activating AMPK/ PGC-1α signalling pathway.

Practical Implications

Therapeutic Potential

Sitagliptin may represent a potential therapeutic agent for promoting axon regrowth and locomotor functional repair following spinal cord injury.

GLP-1R as a Target

GLP-1R stimulation is a viable therapeutic target.

Clinical Translation

The study lays groundwork for future clinical trials assessing sitagliptin or GLP-1R agonists in SCI recovery.

Study Limitations

1
The study is performed on rats.
2
The exact mechanisms by which sitagliptin stimulates GLP-1R are not fully elucidated.
3
Not specified

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