PPAR-α modulates the anti-inflammatory effect of melatonin in the secondary events of spinal cord injury.

Melatonin is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and reduces the development of inflammation and tissue injury events associated with spinal cord trauma. Previous results suggest that Peroxisome proliferator activated receptor alpha- α (PPAR-α), an intracellular transcription factor activated by fatty acids, plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI).

With the aim to characterize the role of PPAR-α in melatonin mediated anti-inflammatory activity, we tested the efficacy of melatonin (30 mg/kg) in an experimental model of spinal cord trauma induced in mice by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-αKO) with wild type (WT) mice.

The results obtained indicate that melatonin -mediated anti-inflammatory activity is weakened in PPAR-α KO mice, as compared to WT controls. In particular, melatonin was less effective in PPAR-α KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, pro-inflammatory cytokine expression, NF-κB activation, inducible nitric-oxide synthase (iNOS) expression. This study indicates that PPAR-α can contribute to the anti-inflammatory activity of melatonin in SCI.