Nature Neuroscience 9, 243 - 250 (2005)
Published online: 25 December 2005; | doi:10.1038/nn1622
Retinoic acid receptor  2 promotes functional regeneration of sensory axons in the spinal cordLiang-Fong Wong1, 4, Ping K Yip2, 4, Anna Battaglia2, John Grist2, Jonathan Corcoran3, Malcolm Maden3, Mimoun Azzouz1, Susan M Kingsman1, Alan J Kingsman1, Nicholas D Mazarakis1
& Stephen B McMahon21
Oxford BioMedica (UK) Ltd., Medawar Centre, Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK. 2
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, Wolfson Wing, Hodgkin Building, King's College London, Guy's Campus, London SE1 1UL, UK. 3
MRC Centre for Developmental Neurobiology, King's College London, New Hunts House, Guy's Campus, London SE1 1UL, UK. 4
These authors contributed equally to this work.
Correspondence should be addressed to Liang-Fong Wong l.wong@oxfordbiomedica.co.uk or Nicholas D Mazarakis n.mazarakis@oxfordbiomedica.co.uk The embryonic CNS readily undergoes regeneration, unlike the adult CNS, which has limited axonal repair after injury. Here we tested the hypothesis that retinoic acid receptor  2 (RAR2), critical in development for neuronal growth, may enable adult neurons to grow in an inhibitory environment. Overexpression of RAR2 in adult rat dorsal root ganglion cultures increased intracellular levels of cyclic AMP and stimulated neurite outgrowth. Stable RAR2 expression in DRG neurons in vitro and in vivo enabled their axons to regenerate across the inhibitory dorsal root entry zone and project into the gray matter of the spinal cord. The regenerated neurons enhanced second-order neuronal activity in the spinal cord, and RAR2-treated rats showed highly significant improvement in sensorimotor tasks. These findings show that RAR2 induces axonal regeneration programs within injured neurons and may thus offer new therapeutic opportunities for CNS regeneration.
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