Changes in spinal GDNF, BDNF, and NT-3 expression after transient spinal cord ischemia in the rat.

Abstract

Previous studies have demonstrated that the expression of several growth factors including glial cell-derived neurotrophic factor (GDNF), brain-derived growth factor (BDNF), and neurotrophin-3 (NT-3) play an important role in defining neuronal survival after brain ischemia. In the present study, using a well-defined model of transient spinal ischemia in rat, we characterized the changes in spinal GDNF, BDNF, and NT-3 expression as defined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence coupled with deconvolution microscopy. In control animals, baseline levels of GDNF, BDNF, and NT-3 (74 +/- 22, 3,600 +/- 270, 593 +/- 176 pg/g tissue, respectively) were measured. In the ischemic group, 6 min of spinal ischemia resulted in a biphasic response with increases in tissue GDNF and BDNF concentrations at the 2-hr and 72-hr points after ischemia. No significant differences in NT-3 concentration were detected. Deconvolution analysis revealed that the initial increase in tissue GDNF concentration corresponded to a neuronal upregulation whereas the late peak seen at 72 hr corresponded with increased astrocyte-derived GDNF synthesis. Increased expression of BDNF was seen in neurons, astrocytes, and oligodendrocytes. These data suggest that the early increase in neuronal GDNF/BDNF expression likely modulates neuronal resistance/recovery during the initial period of postischemic reflow. Increased astrocyte-derived BDNF/GDNF expression corresponds with transient activation of astrocytes and may play an active role in neuronal plasticity after non-injurious intervals of spinal ischemia.

• Authors: Joho Tokumine, Osamu Kakinohana, Dasa Cizkova, Doug W Smith, Martin Marsala
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 74 Issue 4 Pg. 552-61 (Nov 15 2003) ISSN: 0360-4012 [Print] United States
• PMID: 14598299 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• Brain-Derived Neurotrophic Factor
• Gdnf protein, rat
• Glial Cell Line-Derived Neurotrophic Factor
• Nerve Growth Factors
• Neurotrophin 3

Topics

• Animals
• Brain-Derived Neurotrophic Factor (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Glial Cell Line-Derived Neurotrophic Factor
• Male
• Microscopy, Fluorescence
• Nerve Growth Factors (metabolism)
• Neuroglia (metabolism)
• Neuronal Plasticity (physiology)
• Neurons (metabolism)
• Neurotrophin 3 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord Ischemia (metabolism)
• Up-Regulation