Cortical Overexpression of Neuronal Calcium Sensor-1 Induces Functional Plasticity in Spinal Cord Following Unilateral Pyramidal Tract Injury in Rat

PLoS Biology, 2010 · DOI: 10.1371/journal.pbio.1000399 · Published: June 22, 2010

Spinal Cord Injury Neurology Neuroplasticity

Simple Explanation

Following trauma to the central nervous system (brain or spinal cord), neurons show very little capacity to re-grow their axons, which can lead to a permanent loss of function in those regions. In this study, we show that this failure of axon re-growth is associated with low intracellular levels of a small molecule called neuronal calcium sensor-1 (NCS1). These findings demonstrate that increasing the intracellular levels of NCS1 in neurons can aid in the recovery from central nervous system injury, and can help improve behavioural function.

Study Duration

6 weeks

Participants

Adult male Wistar rats

Evidence Level

Level II: Experimental study in rats

Key Findings

1
NCS1 overexpression in uninjured corticospinal neurons exhibited axonal sprouting across the midline into the CST-denervated side of the spinal cord following unilateral pyramidotomy.
2
In injured corticospinal neurons, overexpression of NCS1 induced axonal sprouting and regeneration and also neuroprotection.
3
These findings demonstrate that increasing the levels of intracellular NCS1 in injured and uninjured central neurons enhances their intrinsic anatomical plasticity within the injured adult central nervous system.

Research Summary

This present study demonstrates that the intracellular levels of NCS1 in adult cortical neurons can be significantly elevated by transduction with a lentiviral vector. Similarly, analogous experiments conducted in vivo show that CSN overexpressing NCS1 with intact CST axons can undergo distal collateral sprouting and cross the midline into the CST-denervated side of the spinal cord. Furthermore, studies on the axotomized CSN show that NCS1 overexpression not only induces axonal sprouting and regeneration at the lesion site but also exerts a neuroprotective affect on injured CSN.

Practical Implications

Therapeutic Target

NCS1 emerges as a potential intracellular target for therapeutic intervention following injury to the central nervous system.

Functional Recovery

Overexpression of NCS1 in CSN can induce intact CST to form functional connections in the CST-denervated side of the spinal cord, improving motor function.

Neuroprotection

NCS1 overexpression can increase the intrinsic capacity of CSN to overcome the inhibitory environment and compensate for the lack of trophic support associated with CNS injury.

Study Limitations

1
Study conducted only on rats, further research needed to validate in humans.
2
Intracellular mechanisms for therapies investigated only on purine-sensitive ste20-like protein kinase (Mst3b).
3
The study focused primarily on anatomical and functional outcomes; molecular mechanisms require further investigation.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury