TY - JOUR
T1 - Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism
AU - Cai, Dongming
AU - Yingjing, Shen
AU - De Bellard, Maria Elena
AU - Tang, Song
AU - Filbin, Marie T.
N1 - Funding Information:
We thank Dr. Roger Persell for critically reading this manuscript and Dr. Lloyd Williams for his assistance with the image analysis. This work was supported by a grant from the National Multiple Sclerosis Society, the National Institutes of Health (NS 37060), and a core facility grant from the Research Centers for Minorities Institute-NIH. M. T. F. is the Marie L. Hesselbach Professor of Biological Sciences and is a recipient of an Established Investigator Award from the American Heart Association, New York chapter.
PY - 1999/1
Y1 - 1999/1
N2 - MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the G(i) protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a G(i) protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo.
AB - MAG is a potent inhibitor of axonal regeneration. Here, inhibition by MAG, and myelin in general, is blocked if neurons are exposed to neurotrophins before encountering the inhibitor; priming cerebellar neurons with BDNF or GDNF, but not NGF, or priming DRG neurons with any of these neurotrophins blocks inhibition by MAG/myelin. Dibutyryl cAMP also overcomes inhibition by MAG/myelin, and cAMP is elevated by neurotrophins. A PKA inhibitor present during priming abrogates the block of inhibition. Finally, if neurons are exposed to MAG/myelin and neurotrophins simultaneously, but with the G(i) protein inhibitor, inhibition is blocked. We suggest that priming neurons with particular neurotrophins elevates cAMP and activates PKA, which blocks subsequent inhibition of regeneration and that priming is required because MAG/myelin activates a G(i) protein, which blocks increases in cAMP. This is important for encouraging axons to regrow in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0032960457&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80681-9
DO - 10.1016/S0896-6273(00)80681-9
M3 - Article
C2 - 10027292
AN - SCOPUS:0032960457
VL - 22
SP - 89
EP - 101
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 1
ER -