Adenosine triphosphate promotes locomotor recovery after spinal cord injury by activating mammalian target of rapamycin pathway in rats

Neural Regen Res, 2013 · DOI: 10.3969/j.issn.1673-5374.2013.02.001 · Published: January 1, 2013

Spinal Cord Injury Genetics Regenerative Medicine & Stem Cells

Simple Explanation

This study investigates how adenosine triphosphate (ATP) affects recovery after spinal cord injury (SCI) in rats. It focuses on the mammalian target of rapamycin (mTOR) pathway, which is important for nerve cell growth and function. Rat models of SCI were treated with ATP (to activate mTOR) or rapamycin (to inhibit mTOR). The researchers then observed the rats' ability to move and examined their spinal cord tissue to see how these treatments affected nerve cell growth and related factors. The findings suggest that ATP, by activating the mTOR pathway, helps promote nerve regeneration, reduce harmful inflammation, and improve locomotor function in rats after SCI.

Study Duration

1-4 weeks

Participants

128 adult specific pathogen-free female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
ATP promotes locomotor recovery after spinal cord injury in rats, as demonstrated by improved BBB scores in the ATP group compared to control groups.
2
ATP can activate the Akt/mammalian target of rapamycin pathway (mTOR)/signal transduction and activator of transcription 3 (STAT3) pathway after spinal cord injury in rats, enhancing the expression of key proteins in this pathway.
3
ATP-activated Akt/mTOR/STAT3 pathway contributes to locomotor recovery after spinal cord injury in rats by increasing endogenous neural stem cells, inducing neurogenesis and axonal growth, and inhibiting excessive astrogliosis.

Research Summary

This study investigated the role of ATP-activated mTOR signaling in the physiology and pathology of SCI, with a special focus on molecular targets of upstream, downstream, and inhibitor of mTOR kinase that potentially contributes to neurogenesis and neuropathology. BBB scores, immunohistochemistry, western blot analysis, results showed that ATP can activate Akt/mTOR/STAT3 pathway, increase nestin, NeuN, NSE and NF200 expression but decrease GFAP expression, thereby promoting the locomotor recovery of rats with SCI. Therefore, we confirmed that in vivo ATP promoted locomotor recovery by activating the Akt/mTOR/STAT3 pathway after SCI in rats.

Practical Implications

Therapeutic Potential

ATP and activators of mTOR signaling may be potential therapeutic agents for promoting neurogenesis and locomotor recovery after spinal cord injury.

Drug Development

A better understanding of the molecular mechanisms of downstream and upstream mTOR signaling actions can contribute to developing more accurate pharmacological interventions for SCI.

Combination Therapies

Combining ATP with other treatments that prolong mTOR signaling activation may create conditions conducive to proper neuronal proliferation and differentiation.

Study Limitations

1
The study was conducted on rats, and the results may not be directly applicable to humans.
2
The study focused on the Akt/mTOR/STAT3 pathway, and other pathways may also be involved in locomotor recovery after SCI.
3
The study did not investigate whether extracellular ATP-activated mTOR signaling occurs through P2X7 receptors in the injured spinal cord.

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