Cortical overexpression of neuronal calcium sensor-1 induces functional plasticity in spinal cord following unilateral pyramidal tract injury in rat.
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.
Yip
Ping K
PK
Neurorestoration Group, Wolfson CARD, King's College London, Guy's Campus, London, United Kingdom. ping.yip@kcl.ac.uk
Wong
Liang-Fong
LF
Sears
Thomas A
TA
Yáñez-Muñoz
Rafael J
RJ
McMahon
Stephen B
SB
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D004789:Enzyme Activation; D005822:Genetic Vectors; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D017931:DNA Primers; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins; D011494:Protein Kinases