Growth-associated proteins and regeneration-induced gene expression in the aging neuron.
Axonal elongation and sprouting during regeneration are retarded with aging but the etiology of this is unclear. We investigated whether this age-associated decline is related to a decline in expression of three different growth-associated proteins (GAPs): alpha(1)-tubulin, neurofilament (NF) light subunit (NF-L) and GAP-43. Northern analysis was performed on L4-L5 dorsal root ganglia (DRG) of young (3 months) and aged (23 months) rats following a sciatic nerve crush and compared to their age-matched controls. The results show that initial mRNA levels of alpha(1)-tubulin and NF-L in the control aged rat DRG were half those of the control young adults, whereas expression of GAP-43 was unchanged. Two weeks after axotomy, the expression of alpha(1)-tubulin and GAP-43 in the aged DRG was induced to the same levels as in the axotomized young adult, and the expression of NF-L decreased proportionately in both age groups. These results indicate that certain neuronal mRNAs, such as alpha(1)-tubulin and NF-L may be maintained at lower levels in aging DRG neurons, whereas others, such as GAP-43 appear to be unaltered. However, during regeneration, the aging DRG neuron appears capable of inducing alpha(1)-tubulin, NF-L and GAP-43 as well as the young adult.
Willcox
Bradley J
BJ
Gerontology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Rabb 440, Boston, MA 02215, USA. bjwillcox@phrihawaii.org
Scott
James N
JN
D000375:Aging / Q000502:physiology*; D000818:Animals; D019922:GAP-43 Protein / Q000235:genetics; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D015870:Gene Expression; D008297:Male; D009416:Nerve Regeneration / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016900:Neurofilament Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000235:genetics
D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D014404:Tubulin; C044882:neurofilament protein L