Up-regulation of tyrosine kinase (Trka, Trkb) receptor expression and phosphorylation in lumbosacral dorsal root ganglia after chronic spinal cord (T8-T10) injury.
Previous studies have demonstrated changes in urinary bladder neurotrophic factors after bladder dysfunction. We have hypothesized that retrograde transport of neurotrophin(s) from the bladder to lumbosacral dorsal root ganglia (DRG) may play a role in bladder reflex reorganization after spinal cord injury (SCI). In this study, we determined whether the expression of tyrosine kinase receptors (TrkA, TrkB) is altered in lumbosacral DRG after SCI through immunofluorescence techniques. Complete transection of the spinal cord (T8-T10) was performed in female Wistar rats (120-150 g), and animals were studied 5-6 weeks after SCI. One week before killing, Fast Blue (FB) was injected into the bladder to label bladder afferent cells in the L1, L2, L6, and S1 DRG. After SCI, a significant increase in the number of TrkA-immunoreactive (IR) positive cells was detected in the L6-S1 DRG (L6: 1.9-fold, P < or = 0.01; S1: 1.7-fold, P < or = 0.05) and in the L1 DRG (3.0-fold; P < or = 0.01) but not in the L4-L5 DRG compared with spinal-intact (control) rats. After SCI, a significant increase in the number of TrkB-IR cells was also detected in the L6-S1 DRG (L6: 2.2-fold, P < or = 0.01; S1: 1.5-fold, P < or = 0.05) and in the L1-L2 DRG (L1: 1.5-fold, P < or = 0.01; L2: 1.3-fold, P < or = 0.05) but not in the L4-L5 DRG compared with control rats. After SCI, the percentage of FB-labeled cells expressing TrkA immunoreactivity (approximately 68%) or TrkB immunoreactivity (approximately 65%) in L1 and L6 DRG significantly (P < or = 0.01) increased compared with control (20-30%) DRG. After SCI, the percentage of TrkA-IR cells expressing phosphorylated (p)-Trk immunoreactivity significantly increased (1.5- to 2.3-fold increase) in the L1, L6, and S1 DRG. The percentage of TrkB-IR cells expressing p-Trk immunoreactivity after SCI also increased (1.3-fold increase) in the L1 and L6 DRG. These results demonstrate that (1) TrkA and TrkB immunoreactivity is increased in bladder afferent cells after SCI and (2) TrkA and TrkB receptors are phosphorylated in DRG after SCI. Neuroplasticity of lower urinary tract reflexes after SCI may be mediated by both nerve growth factor and brain-derived neurotrophic factor.
Qiao
Liya
L
Department of Neurology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Vizzard
Margaret A
MA
D000818:Animals; D002908:Chronic Disease; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D007150:Immunohistochemistry; D008161:Lumbosacral Region; D009475:Neurons, Afferent / Q000378:metabolism; D009929:Organ Size; D010766:Phosphorylation; D051381:Rats / Q000378:metabolism*; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013904:Thoracic Vertebrae; D015854:Up-Regulation; D001743:Urinary Bladder / Q000294:innervation / Q000473:pathology
D020917:Receptor, trkA; D020813:Receptor, trkB