PPAR-a Modulates the Anti-Inflammatory Effect of Melatonin in the Secondary Events of Spinal Cord Injury.

Molecular neurobiology

PubMedID: 27686077

Paterniti I, Campolo M, Cordaro M, Impellizzeri D, Siracusa R, Crupi R, Esposito E, Cuzzocrea S. PPAR-a Modulates the Anti-Inflammatory Effect of Melatonin in the Secondary Events of Spinal Cord Injury. Mol Neurobiol. 2016;.
Melatonin is the principal secretory product of the pineal gland, and its role as an immunomodulator 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 a (PPAR-a), a nuclear receptor protein that functions as a 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-a 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-a (PPAR-a KO) with wild-type (WT) mice. THE RESULTS
obtained indicate that melatonin-mediated anti-inflammatory activity is weakened in PPAR-a KO mice, as compared to WT controls.In particular, melatonin was less effective in PPAR-a 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, nuclear factor ?B (NF-?B) activation, and inducible nitric oxide synthase (iNOS) expression. This study indicates that PPAR-a can contribute to the anti-inflammatory activity of melatonin in SCI.