Retinoic acid receptor beta2 promotes functional regeneration of sensory axons in the spinal cord.
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 beta2 (RARbeta2), critical in development for neuronal growth, may enable adult neurons to grow in an inhibitory environment. Overexpression of RARbeta2 in adult rat dorsal root ganglion cultures increased intracellular levels of cyclic AMP and stimulated neurite outgrowth. Stable RARbeta2 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 RARbeta2-treated rats showed highly significant improvement in sensorimotor tasks. These findings show that RARbeta2 induces axonal regeneration programs within injured neurons and may thus offer new therapeutic opportunities for CNS regeneration.
Wong
Liang-Fong
LF
Oxford BioMedica (UK) Ltd., Medawar Centre, Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK. l.wong@oxfordbiomedica.co.uk
Yip
Ping K
PK
Battaglia
Anna
A
Grist
John
J
Corcoran
Jonathan
J
Maden
Malcolm
M
Azzouz
Mimoun
M
Kingsman
Susan M
SM
Kingsman
Alan J
AJ
Mazarakis
Nicholas D
ND
McMahon
Stephen B
SB
D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000293:injuries / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*
D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta