Pigment Epithelium-Derived Factor Promotes Axon Regeneration and Functional Recovery After Spinal Cord Injury.

Abstract

Although neurons in the adult mammalian CNS are inherently incapable of regeneration after injury, we previously showed that exogenous delivery of pigment epithelium-derived factor (PEDF), a 50-kDa neurotrophic factor (NTF), promoted adult retinal ganglion cell neuroprotection and axon regeneration. Here, we show that PEDF and other elements of the PEDF pathway are highly upregulated in dorsal root ganglion neurons (DRGN) from regenerating dorsal column (DC) injury paradigms when compared with non-regenerating DC injury models. Exogenous PEDF was neuroprotective to adult DRGN and disinhibited neurite outgrowth, whilst overexpression of PEDF after DC injury in vivo promoted significant DC axon regeneration with enhanced electrophysiological, sensory, and locomotor function. Our findings reveal that PEDF is a novel NTF for adult DRGN and may represent a therapeutically useful factor to promote functional recovery after spinal cord injury.

• Authors: Andrew R Stevens, Umar Ahmed, Vasanthy Vigneswara, Zubair Ahmed
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 56 Issue 11 Pg. 7490-7507 (Nov 2019) ISSN: 1559-1182 [Electronic] United States
• PMID: 31049830 (Publication Type: Journal Article)

Chemical References

• Eye Proteins
• Nerve Growth Factors
• RNA, Messenger
• Receptors, Nerve Growth Factor
• Serpins
• pigment epithelium-derived factor

Topics

• Animals
• Axons (drug effects, physiology)
• Cell Survival (drug effects)
• Disease Models, Animal
• Eye Proteins (pharmacology)
• Female
• Ganglia, Spinal (drug effects, metabolism)
• Nerve Growth Factors (metabolism, pharmacology)
• Nerve Regeneration (drug effects)
• Neurites (drug effects, metabolism)
• Neuroprotection (drug effects)
• RNA, Messenger (genetics, metabolism)
• Rats, Sprague-Dawley
• Receptors, Nerve Growth Factor (metabolism)
• Recovery of Function (drug effects)
• Sciatic Nerve (drug effects, physiopathology)
• Serpins (pharmacology)
• Signal Transduction (drug effects)
• Spinal Cord Injuries (pathology, physiopathology)
• Up-Regulation (drug effects)