Figure 12. NCS1 overexpression induces neuroprotection in axotomized corticospinal neurons after pyramidotomy.

Photomicrographs of corticospinal neurons (CSN) in coronal sections of the sensorimotor cortex following a unilateral intracortical injection of lentivector and a pyramidotomy. Fast Blue retrograde tracer was injected into the lesion site to enable identification of CSN at the sensorimotor cortex. In unlesioned rats, Fast Blue was injected into the pyramidal tract carefully to minimise any lesioning effect. Cortical sections were immunostained for NCS1 (red) and GFP (green). The Fast Blue tracer was visible without the need of immunostaining (blue). (A–C) In unlesioned rats, CSN with large healthy somata (arrows) can be observed with low NCS1 and no GFP immunostaining. (D–F) In contrast, the control HIV-GFP-transduced rats with a pyramidotomy have CSN with severely shrunken somata with GFP (arrows) or without GFP (arrowhead) labelling. (G–I) In HIV-GFP-NCS1-transduced rats with a pyramidotomy, GFP-labelled CSN with elevated NCS1 expression have similar somata size as the unlesioned rats (arrows). (J–K) Cell size distributions of CSN determined from colabelled Fast Blue and GFP (Fast Blue alone for unlesioned rats) neurons. The CSN from control HIV-GFP- (black bar and line) but not HIV-GFP-NCS1- (red bar and line) transduced rats had undergone significant atrophy, causing a leftward shift in the cell size distribution towards the small cell areas compared to the CSN from unlesioned rats (white bar and dotted line). Statistical significance of p<0.05 was obtained using the Kolmogorov-Smirnov test.