Differential changes in brain-derived neurotrophic factor and extracellular signal-regulated kinase in rat primary afferent pathways with colitis.
Brain-derived neurotrophic factor (BDNF) has been postulated to participate in inflammation-induced visceral hypersensitivity by modulating the sensitivity of visceral afferents through the activation of intracellular signalling pathways such as the extracellular signal-regulated kinase (ERK) pathway. In the current study, we assessed the expression levels of BDNF and phospho-ERK in lumbosacral dorsal root ganglia (DRG) and spinal cord before and during tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in rats with real-time PCR, ELISA, western blot and immunohistochemical techniques. BDNF mRNA and protein levels were increased in L1 and S1 but not L6 DRG when compared with control (L1: two- to five-fold increases, P < 0.05; S1: two- to three-fold increases, P < 0.05); however, BDNF protein but not mRNA level was increased in L1 and S1 spinal cord when compared with control. In parallel, TNBS colitis significantly induced phospho-ERK1/2 expression in L1 (four- to five-fold, P < 0.05) and S1 (two- to three-fold, P < 0.05) but not in L6 spinal cord levels. Immunohistochemistry results showed that the increase in phospho-ERK1/2 expression occurred at the region of the superficial dorsal horn and grey commisure of the spinal cord. In contrast, there was no change in phospho-ERK5 in any level of the spinal cord examined during colitis. The regional and time-specific changes in the levels of BDNF mRNA, protein and phospho-ERK with colitis may be a result of increased transcription of BDNF in DRG and anterograde transport of BDNF from DRG to spinal cord where it activates intracellular signalling molecules such as ERK1/2.
Qiao
L-Y
LY
Department of Physiology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0551, USA. lqiao2@vcu.edu
Gulick
M A
MA
Bowers
J
J
Kuemmerle
J F
JF
Grider
J R
JR
D000344:Afferent Pathways / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D008161:Lumbosacral Region; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D019208:Brain-Derived Neurotrophic Factor; D014302:Trinitrobenzenesulfonic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7