Differences in neurotrophic factor gene expression profiles between neonate and adult rat spinal cord after injury.
The capacity of the central nervous system for axonal growth decreases as the age of the animal at the time of injury increases. Changes in the expression of neurotrophic factors within embryonic and early postnatal spinal cord suggest that a lack of trophic support contributes to this restrictive growth environment. We examined neurotrophic factor gene profiles by ribonuclease protection assay in normal neonate and normal adult spinal cord and in neonate and adult spinal cord after injury. Our results show that in the normal developing spinal cord between postnatal days 3 (P3) and P10, compared to the normal adult spinal cord, there are higher levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and glial-derived neurotrophic factor (GDNF) mRNA expression and a lower level of ciliary neurotrophic factor (CNTF) mRNA expression. Between P10 and P17, there is a significant decrease in the expression of NGF, BDNF, NT-3, and GDNF mRNA and a contrasting steady and significant increase in the level of CNTF mRNA expression. These findings show that there is a critical shift in neurotrophic factor expression in normal developing spinal cord between P10 and P17. In neonate spinal cord after injury, there is a significantly higher level of BDNF mRNA expression and a significantly lower level of CNTF mRNA expression compared to those observed in the adult spinal cord after injury. These findings suggest that high levels of BDNF mRNA expression and low levels of CNTF mRNA expression play important roles in axonal regrowth in early postnatal spinal cord after injury.
Nakamura
M
M
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.
Bregman
B S
BS
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D020934:Ciliary Neurotrophic Factor / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020932:Nerve Growth Factor / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D020933:Neurotrophin 3 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D020932:Nerve Growth Factor; C073922:neurotrophin 4