Selective loss of NGF-sensitive neurons following experimental colitis.
Nerve growth factor (NGF) enhances neuronal survival during injury to the mature central and peripheral nervous systems, but its potential as a neuroprotective factor in the enteric nervous system (ENS) has not been examined. We used the trinitrobenzene sulfonic acid (TNBS)-induced model of colitis to examine if NGF-sensitive neurons were selectively spared from inflammation-induced cell loss. Immunocytochemistry of whole mounts of the rat colon showed that total myenteric neuronal number decreased by 32.9% +/- 1.4% by 35 days after inflammation. At this time, the proportion of neurons expressing both the p75 and trkA receptor decreased to 38.4% from a control value of 62.0%. The distribution of expression of neural phenotypes among the NGF receptor-expressing population was differentially affected by inflammation, with selective decrease among cholinergic excitatory neurons and calbindin-expressing neurons, and a trend to increase among inhibitory nitrergic neurons. This is evidence of a novel mechanism whereby intestinal inflammation can give rise to a permanent imbalance between excitatory and inhibitory neural pathways, thus tending to compromise intestinal function.
Lin
A
A
Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada K7L 5G2.
Lourenssen
S
S
Stanzel
R D P
RD
Blennerhassett
M G
MG
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D064026:Calbindins; D002452:Cell Count; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000473:pathology*; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000187:drug effects / Q000473:pathology*; D008297:Male; D020932:Nerve Growth Factor / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis; D020917:Receptor, trkA / Q000096:biosynthesis; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis; D014302:Trinitrobenzenesulfonic Acid
D015415:Biomarkers; D064026:Calbindins; D020800:Receptor, Nerve Growth Factor; D064030:S100 Calcium Binding Protein G; D014302:Trinitrobenzenesulfonic Acid; D020932:Nerve Growth Factor; D020917:Receptor, trkA