title: Myenteric expression of nerve growth factor and the p75 neurotrophin receptor regulate axonal remodeling as a consequence of colonic inflammation in mice.
abstract: Nerve growth factor (NGF) levels increase in response to inflammation of the mammalian colon. The precise cellular sources of colonic NGF synthesis, however, remain elusive. Using lines of transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the NGF promoter, we found a subpopulation of adendritic EGFP(+) neurons in the myenteric plexus. These colonic EGFP(+) neurons display positive immunostaining for calretinin but not nitric oxide synthase 1 (NOS1) two biomarkers of mouse myenteric neurons. A loss of NGF expression in null mutant postnatal mice does not affect the survival of these EGFP(+) neurons. Induction of colonic inflammation confirms local increases in NGF mRNA/protein levels, which coincide with heightened detection of EGFP by myenteric neurons. Though NOS1(+) myenteric neurons display positive immunostaining for trkA (the receptor required for NGF binding/signaling), transgenic overexpression of NGF by smooth muscle cells in the colon does not alter the survival, somal size, or axonal density of trkA-expressing NOS1(+) myenteric neurons. Mice lacking functional p75NTR (the second receptor required for NGF binding) exhibit significantly less axonal damage among NOS1(+) myenteric neurons, in response to chemically induced colonic inflammation. Likewise, trkA-expressing sympathetic axons that innervate the myenteric ganglia display less damage in the absence of p75NTR. These data are the first to implicate calretinin(+) myenteric neurons as a source of NGF in the murine colon, and that in response to colonic inflammation, increases in NGF can exaggerate damage of intrinsic NOS1(+) axons and extrinsic sympathetic axons that co-express trkA and p75NTR.
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Casey N
authors.initials: CN
authors.lastname: Petrie
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Armitage
authors.affiliation: Centre for Neuroscience Studies, Queen's University, Kingston, ON K7L 3N6, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. Electronic address: kawajam@queensu.ca.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kawaja
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D064032:Calbindin 2 / Q000378:metabolism; D003092:Colitis / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009197:Myenteric Plexus / Q000473:pathology*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000199:Actins; D064032:Calbindin 2; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D014446:Tyrosine 3-Monooxygenase
keywords: Myenteric; Nerve growth factor; P75 neurotrophin receptor; Sympathetic