The Role of Nerve Growth Factor During Chronic Inflammation of the Descending Colon In Vivo: a Novel Source for Nerve Growth Factor
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In these experiments, we primarily investigate the role and source of nerve growth factor (NGF) in peripheral tissues undergoing chronic inflammation. It has been previously determined that there is a significant increase in the levels of NGF following prolonged inflammation of the urinary bladder or the colon, and the first of two projects discussed here mimics this increase with transgenic mice which ectopically produce NGF under control of the smooth muscle alpha-actin promoter. It was determined by this increase that a p75-sensitive increase in sympathetic innervation occurs when an abundance of NGF is produced locally in the descending colon. Sensory innervation in the colon was found to come from two unique populations, one of which increased following heightened NGF levels. The urinary bladders of NGF overexpressing mice were determined to have an increase in sensory axonal density. The second project described here features chemically induced colonic inflammation and observes the nervous and growth factor changes as a response. Transgenic reporter mice are used to observe the cellular source of NGF in the descending colon, which unexpectedly was determined to be Dogiel type II (DgII neurons) based on morphological and chemical characteristics. We report the increase in NGF mRNA and protein observed following a brief 5-day colonic inflammation, and note that there is no increase in axonal density observed. The chemical inflammation did, however, induce an increase in axonal varicosities, used as a measure of axon damage. Finally, a heterozygous null-mutation of NGF was made in a line of transgenic mice to observe changes in local sensory neurons, sympathetic innervation or NGF protein production, but no differences between the heterozygous null mutants and age-matched wild-type siblings were observed.