Treatment of chronically injured spinal cord with neurotrophic factors stimulates betaII-tubulin and GAP-43 expression in rubrospinal tract neurons.
Exogenous neurotrophic factors provided at a spinal cord injury site promote regeneration of chronically injured rubrospinal tract (RST) neurons into a peripheral nerve graft. The present study tested whether the response to neurotrophins is associated with changes in the expression of two regeneration-associated genes, betaII-tubulin and growth-associated protein (GAP)-43. Adult female rats were subjected to a right full hemisection lesion via aspiration of the C3 spinal cord. A second aspiration lesion was made 4 weeks later and gel foam saturated in brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), or phosphate-buffered saline (PBS) was applied to the lesion site for 60 min. Using in situ hybridization, RST neurons were examined for changes in mRNA levels of betaII-tubulin and GAP-43 at 1, 3, and 7 days after treatment. Based on analysis of gene expression in single cells, there was no effect of BDNF treatment on either betaII-tubulin or GAP-43 mRNA expression at any time point. betaII-Tubulin mRNA levels were enhanced significantly at 1 and 3 days in animals treated with GDNF relative to levels in animals treated with PBS. Treatment with GDNF did not affect GAP-43 mRNA levels at 1 and 3 days, but at 7 days there was a significant increase in mRNA expression. Interestingly, 7 days after GDNF treatment, the mean cell size of chronically injured RST neurons was increased significantly. Although GDNF and BDNF both promote axonal regeneration by chronically injured neurons, only GDNF treatment is associated with upregulation of betaII-tubulin or GAP-43 mRNA. It is not clear from the present study how exogenous BDNF stimulates regrowth of injured axons.
Department of Anatomy and Neurobiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Paul D
PD
Storer
Dirk
D
Dolbeare
John D
JD
Houle
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D048429:Cell Size; D002908:Chronic Disease; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014404:Tubulin