PMID- 22921460 OWN - NLM STAT- MEDLINE DCOM- 20130121 LR - 20211021 IS - 1090-2430 (Electronic) IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 238 IP - 2 DP - 2012 Dec TI - Up-regulation of brain-derived neurotrophic factor is regulated by extracellular signal-regulated protein kinase 5 and by nerve growth factor retrograde signaling in colonic afferent neurons in colitis. PG - 209-17 LID - S0014-4886(12)00316-0 [pii] LID - 10.1016/j.expneurol.2012.08.007 [doi] AB - Brain-derived neurotrophic factor (BDNF) plays an essential role in sensory neuronal activation in response to visceral inflammation. Here we report that BDNF up-regulation in the primary afferent neurons in the dorsal root ganglia (DRG) in a rat model of colitis is mediated by the activation of endogenous extracellular signal-regulated protein kinase (ERK) 5 and by nerve growth factor (NGF) retrograde signaling. At 7 days of colitis, the expression level of BDNF is increased in conventional neuronal tracing dye Fast Blue labeled primary afferent neurons that project to the distal colon. In these neurons, the phosphorylation (activation) level of ERK5 is also increased. In contrast, the level of phospho-ERK1/2 is not changed in the DRG during colitis. Prevention of the ERK5 activation in vivo with an intrathecal application of the MEK inhibitor PD98059 significantly attenuates the colitis-induced increases in BDNF expression in the DRG. Further studies show that BDNF up-regulation in the DRG is triggered by NGF retrograde signaling which also involves activation of the MEK/ERK pathways. Application of exogenous NGF exclusively to the compartment containing DRG nerve terminals in an ex vivo ganglia-nerve preparation markedly increases the BDNF expression level in the DRG neuronal cell body that is placed in a different compartment; this BDNF elevation is attenuated by U0126, PD98059 and a specific ERK5 inhibitor BIX02188. These results demonstrate the mechanisms and pathways by which BDNF expression is elevated in primary sensory neurons following visceral inflammation that is mediated by increased activity of ERK5 and is likely to be triggered by the elevated NGF level in the inflamed viscera. CI - Published by Elsevier Inc. FAU - Yu, Sharon J AU - Yu SJ AD - Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA. FAU - Grider, John R AU - Grider JR FAU - Gulick, Melisa A AU - Gulick MA FAU - Xia, Chun-mei AU - Xia CM FAU - Shen, Shanwei AU - Shen S FAU - Qiao, Li-Ya AU - Qiao LY LA - eng GR - DK034153/DK/NIDDK NIH HHS/United States GR - R01 DK034153/DK/NIDDK NIH HHS/United States GR - R01 DK077917/DK/NIDDK NIH HHS/United States GR - DK077917/DK/NIDDK NIH HHS/United States GR - R56 DK034153/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120819 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Amidines) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Diterpenes) RN - 0 (Enzyme Inhibitors) RN - 0 (diamidino compound 253-50) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) RN - 9061-61-4 (Nerve Growth Factor) RN - A5O6P1UL4I (resiniferatoxin) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7) SB - IM MH - Amidines MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/immunology/*metabolism MH - Colitis/chemically induced/*pathology MH - Colon/innervation/*pathology MH - Disease Models, Animal MH - Diterpenes/pharmacology MH - Enzyme Inhibitors/pharmacology/therapeutic use MH - Enzyme-Linked Immunosorbent Assay MH - Ganglia, Spinal/pathology MH - Male MH - Mitogen-Activated Protein Kinase 7/*metabolism MH - Nerve Growth Factor/immunology MH - Neurons, Afferent/drug effects/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects/*physiology MH - Time Factors MH - Trinitrobenzenesulfonic Acid/toxicity MH - Up-Regulation/drug effects/*physiology PMC - PMC3498573 MID - NIHMS401949 COIS- Conflict of Interest: All authors claim no conflict of interest EDAT- 2012/08/28 06:00 MHDA- 2013/01/23 06:00 PMCR- 2013/12/01 CRDT- 2012/08/28 06:00 PHST- 2012/04/04 00:00 [received] PHST- 2012/07/25 00:00 [revised] PHST- 2012/08/03 00:00 [accepted] PHST- 2012/08/28 06:00 [entrez] PHST- 2012/08/28 06:00 [pubmed] PHST- 2013/01/23 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - S0014-4886(12)00316-0 [pii] AID - 10.1016/j.expneurol.2012.08.007 [doi] PST - ppublish SO - Exp Neurol. 2012 Dec;238(2):209-17. doi: 10.1016/j.expneurol.2012.08.007. Epub 2012 Aug 19.