BDNF induces late-phase LTP of C-fiber evoked field potentials in rat spinal dorsal horn.
Several lines of evidence have shown that in some brain regions brain-derived neurotrophic factor (BDNF) is important for long-term potentiation (LTP), a synaptic model of memory storage. In the present work we evaluate the role of BDNF in LTP of C-fiber evoked field potentials in spinal dorsal horn, a synaptic model of pain memory. We found that spinal application of BDNF-induced LTP of C-fiber evoked field potentials with a long latency, lasting for >8 h, and the effect was blocked by either tyrosine kinase inhibitor (K252a) or BNDF scavenger (TrkB-Fc). The potentiation produced by BDNF was occluded by late-phase LTP (L-LTP) but not by early-phase LTP (E-LTP) induced by electrical stimulation. Pretreatment of K252a or TrkB-Fc selectively blocked spinal L-LTP induced by low-frequency stimulation (LFS) but not E-LTP. BDNF-induced LTP was completely abolished by the protein synthesis inhibitor (anisomycin), by N-methyl-D-aspartate (NMDA) receptor blocker (MK-801), by extracellular signal-regulated protein kinase (ERK) inhibitor (PD98059) or by p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580) but not by c-Jun N-terminal kinase (JNK) inhibitor (SP600125). Nuclear factor-kappaB (NF-kappaB) inhibitor (PDTC) also suppressed spinal BDNF-LTP. The results suggest that BDNF play a crucial role in protein synthesis-dependent L-LTP in spinal dorsal horn via activation of ERK, p38 MAPK and NF-kappaB signal pathways.
Pain Research Center and Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 510089 Guangzhou, China.
Li-Jun
LJ
Zhou
Yi
Y
Zhong
Wen-Jie
WJ
Ren
Yong-Yong
YY
Li
Tong
T
Zhang
Xian-Guo
XG
Liu
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026121:Indole Alkaloids / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008297:Male; D016328:NF-kappa B / Q000494:pharmacology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D020813:Receptor, trkB / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*
D000873:Anthracenes; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D016328:NF-kappa B; C432165:pyrazolanthrone; C049985:staurosporine aglycone; D020813:Receptor, trkB