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PLoS Biol. 2010 Jun 22;8(6):e1000399. doi: 10.1371/journal.pbio.1000399.

Cortical overexpression of neuronal calcium sensor-1 induces functional plasticity in spinal cord following unilateral pyramidal tract injury in rat.

Author information

1
Neurorestoration Group, Wolfson CARD, King's College London, Guy's Campus, London, United Kingdom. ping.yip@kcl.ac.uk

Abstract

Following trauma of the adult brain or spinal cord the injured axons of central neurons fail to regenerate or if intact display only limited anatomical plasticity through sprouting. Adult cortical neurons forming the corticospinal tract (CST) normally have low levels of the neuronal calcium sensor-1 (NCS1) protein. In primary cultured adult cortical neurons, the lentivector-induced overexpression of NCS1 induces neurite sprouting associated with increased phospho-Akt levels. When the PI3K/Akt signalling pathway was pharmacologically inhibited the NCS1-induced neurite sprouting was abolished. The overexpression of NCS1 in uninjured corticospinal neurons exhibited axonal sprouting across the midline into the CST-denervated side of the spinal cord following unilateral pyramidotomy. Improved forelimb function was demonstrated behaviourally and electrophysiologically. In injured corticospinal neurons, overexpression of NCS1 induced axonal sprouting and regeneration and also neuroprotection. 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.

PMID:
20585375
PMCID:
PMC2889931
DOI:
10.1371/journal.pbio.1000399
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors Ping K. Yip, Liang-Fong Wong and Stephen McMahon would like to declare competing financial interests in relation to this work. There is a patent application submitted by King's College London and Oxford BioMedica Ltd entitled: System for delivering neuronal calcium sensor-1 (NCS-1) (International Application No.: PCT/GB2006/003367). The abstract on the application is: The present invention provides a system capable of delivering neuronal calcium sensor-1 (NCS-1), or a nucleotide sequence encoding NCS-1 to a target cell, for promoting neurite outgrowth. The system may be used in the manufacture of a pharmaceutical composition for the treatment of a condition such as spinal cord injury.

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