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Treatment of chronically injured spinal cord with neurotrophic factors stimulates βII‐tubulin and GAP‐43 expression in rubrospinal tract neurons
Author(s) -
Storer Paul D.,
Dolbeare Dirk,
Houle John D.
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10787
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , neurotrophin , spinal cord , lesion , in situ hybridization , brain derived neurotrophic factor , endocrinology , medicine , biology , spinal cord injury , neuroscience , messenger rna , pathology , receptor , biochemistry , gene
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, βII‐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 βII‐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 βII‐tubulin or GAP‐43 mRNA expression at any time point. βII‐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 βII‐tubulin or GAP‐43 mRNA. It is not clear from the present study how exogenous BDNF stimulates regrowth of injured axons. © 2003 Wiley‐Liss, Inc.