Prohibitin 1 gene delivery promotes functional recovery in rats with spinal cord injury.

Abstract

Spinal cord injury (SCI) represents a severe health problem worldwide usually associated with severe disability and reduced quality of life. The aim of this work was to investigate the role of prohibitin 1 (PHB1) in the progression of SCI in rats. Firstly, we observed that expression of PHB1 was downregulated following SCI in rats. Then, we hypothesized that PHB1 overexpression by delivery of Ad-PHB1 could result in neuroprotection and promote functional recovery following SCI. Briefly, Wistar rats received a 35-g clip-compression injury and were administered Ad-PHB1 or Ad immediately following SCI. It was found that Ad-PHB1 administration significantly improved locomotor function and increased pain tolerance in rats with SCI. Furthermore, Ad-PHB1 administration following SCI attenuated axonal degradation and increased neuron sparing. Ad-PHB1 administration following SCI reduced apoptosis through inhibiting the Bcl-2/Bax/caspase-3 pathway. Ad-PHB1 administration following SCI suppressed endoplasmic reticulum stress, evidenced by reduced mRNA levels of CCAAT enhancer binding protein homologous protein, chaperone-ucose-regulated protein 78, and X-box protein 1. Ad-PHB1 administration following SCI restored mitochondrial adenosine triphosphate formation, reduced reactive oxygen species formation, and improved mitochondrial respiration rates. Finally, Ad-PHB1 administration following SCI activated downstream signals including phosphatidylinositol-3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK1/2), and nuclear factor-kappaB. These data indicate that the PHB1 plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.

• Authors: L Li, J-D Guo, H-D Wang, Y-M Shi, Y-L Yuan, S-X Hou
• Journal: Neuroscience (Neuroscience) Vol. 286 Pg. 27-36 (Feb 12 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 25463519 (Publication Type: Journal Article)
• Copyright: Copyright © 2015. Published by Elsevier Ltd.

Chemical References

• Neuroprotective Agents
• Prohibitins
• Repressor Proteins

Topics

• Adenoviridae
• Animals
• Apoptosis (drug effects)
• Disease Progression
• Endoplasmic Reticulum Stress (drug effects)
• Female
• Genetic Vectors
• Hyperalgesia (drug therapy)
• Locomotion (drug effects)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (metabolism, therapeutic use)
• Prohibitins
• Rats
• Rats, Wistar
• Recovery of Function (drug effects)
• Repressor Proteins (genetics, metabolism, therapeutic use)
• Signal Transduction (drug effects)
• Spinal Cord Injuries (drug therapy, genetics, metabolism)