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Trk Moves on Track: retrograde transport of TrkA mediates sensory neuroplasticity in experimental colitis
Author(s) -
QIAO LIYA,
Yu Sharon,
Gulick Melisa,
Xia Chunmei
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.701.13
Subject(s) - tropomyosin receptor kinase a , neurotrophin , nerve growth factor , resiniferatoxin , trk receptor , neuroscience , neurotrophic factors , brain derived neurotrophic factor , dorsal root ganglion , low affinity nerve growth factor receptor , mapk/erk pathway , tropomyosin receptor kinase b , medicine , endocrinology , chemistry , microbiology and biotechnology , kinase , sensory system , receptor , biology , trpv1 , transient receptor potential channel
The prototypical neurotrophin nerve growth factor (NGF) has long been known to mediate visceral hypersensitivity caused by inflammation. By employing spinal nerve ligation or by prolonged pre‐treatment with resiniferatoxin (RTX) to desensitize primary afferent neurons, we demonstrate that in the rat TNBS‐induced colonic inflammation causes elevation of NGF in the distal colon where NGF binds to its high affinity receptor, TrkA. The NGF/TrkA complex is then retrogradely transported to the colonic afferent neurons in the dorsal root ganglia (DRG), and induces neuroplasticity by activating extracellular signal‐regulated protein kinase (ERK) 5, the big MAP kinase 1 (BMK1), as well as upregulating brain‐derived neurotrophic factor (BDNF). In these specifically labeled colonic afferent neurons, the phosphorylation level of ERK1/2 is not changed. BDNF up‐regulation in the colonic afferent neurons is significantly attenuated by blockade of ERK5 in vivo by intrathecal injection of a specific MEK inhibitor PD98059. Blockade of ERK5 activity in the ex vivo ganglia‐nerve two compartmented culture also inhibits retrograde NGF‐induced BDNF up‐regulation in the neuronal soma. These findings imply that colonic NGF regulates visceral hypersensitivity through retrograde activation of colonic primary afferent neurons in the DRG involving ERK5‐mediated BDNF up‐regulation. NIDDK DK077917