Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury

Qiang Li1, Shane Gao2, Zhanrong Kang3

  • 1Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Frontiers in Neuroscience
|December 19, 2018
PubMed

Insights

Rapamycin enhances mitophagy and reduces apoptosis in spinal cord injury models. This neuroprotective effect improves locomotor function, suggesting rapamycin as a potential therapy for spinal cord injury.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Spinal cord ischemia-reperfusion (I/R) injury poses a significant threat to the central nervous system.
  • Mitochondria are key targets in I/R injury.
  • Rapamycin's neuroprotective potential via autophagy is recognized, but its role in spinal cord injury-induced mitophagy and apoptosis is unclear.

Purpose of the Study:

  • To investigate rapamycin's effect on mitophagy and mitochondria-dependent apoptosis in a mouse model of spinal cord ischemia-reperfusion injury (SCIRI).

Main Methods:

  • Utilized a SCIRI mouse model.
  • Assessed mitophagy by measuring p62 and Parkin translocation to damaged mitochondria.
  • Evaluated mitochondrial apoptosis by analyzing Apaf-1, Caspase-3, Caspase-9 expression, Bax translocation, and cytochrome c release.
  • Quantified TUNEL-positive cells and assessed locomotor function 24 hours post-SCIRI.

Main Results:

  • Rapamycin significantly enhanced mitophagy, evidenced by increased p62 and Parkin translocation.
  • Rapamycin significantly reduced mitochondrial apoptosis markers, inhibiting Bax translocation and cytochrome c release.
  • Rapamycin treatment decreased TUNEL-positive cells and improved locomotor function in SCIRI mice.

Conclusions:

  • Rapamycin promotes mitophagy and attenuates SCIRI-induced apoptosis.
  • Rapamycin improves locomotor function following spinal cord injury.
  • Rapamycin demonstrates potential as a therapeutic agent for spinal cord injury.

Related Concept Videos

Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
18.4K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
14.5K
Self-Evaluation: Self-Enhancement and Self-Verification03:00

Self-Evaluation: Self-Enhancement and Self-Verification

Social psychologists have documented that feeling good about ourselves and maintaining positive self-esteem is a powerful motivator of human behavior (Tavris & Aronson, 2008). In the United States, members of the predominant culture typically think very highly of themselves and view themselves as good people who are above average on many desirable traits (Ehrlinger, Gilovich, & Ross, 2005). Often, our behavior, attitudes, and beliefs are affected when we experience a threat to our...
5.8K
Bioavailability Enhancement: Drug Solubility Enhancement01:16

Bioavailability Enhancement: Drug Solubility Enhancement

Body:Bioavailability is a critical factor in determining a drug's effectiveness. It refers to the proportion of a drug that enters the circulation when introduced into the body and is, as a result, able to have an active effect. Enhancing bioavailability is essential for drugs with poor solubility, as it can significantly impact their therapeutic efficacy. Various methods are employed to increase the solubility of drugs, thereby enhancing their bioavailability.Micronization and nanonization are...
259
Bioavailability Enhancement: Drug Permeability Enhancement01:27

Bioavailability Enhancement: Drug Permeability Enhancement

Body:After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt...
205
Spinal Cord01:26

Spinal Cord

The spinal cord, a critical component of the central nervous system, extends from the base of the brainstem to the lumbar region of the vertebral column. It is essential for maintaining physical stability and facilitating communication between the brain and peripheral parts of the body.
1.9K