title: Prolonged exposure to elevated levels of endogenous nerve growth factor affects the morphological and neurochemical features of sympathetic neurons of postnatal and adult mice.
abstract: It is well documented that acute increases of target-derived nerve growth factor affect the morphological and neurochemical features of post-ganglionic sympathetic neurons. It has yet to be determined, however, whether similar changes are still evident after prolonged exposure to increased levels of endogenous nerve growth factor. Using a transgenic line of mice which overexpresses nerve growth factor in the brain commencing after the first week of postnatal life and continuing into adulthood, we have shown previously that sympathetic axons sprout into the nerve growth factor-rich cerebellum of these animals; no such axons are seen in the cerebellum of age-matched wild type animals. The aim of this study was to examine and characterize the effects of chronically elevated levels of endogenous nerve growth factor on sympathetic neurons of the superior cervical ganglion. In comparison to adult wild type mice, adult transgenic animals possessed hypertrophied ganglia which displayed both an increase in sympathetic somal size and a decrease in their density. At the electron microscope level, sympathetic somata of the adult transgenic animals had numerous electron-dense lysosome-like structures in the cytoplasm, as compared to that seen in the sympathetic somata of adult wild type animals. Immunodetection of nerve growth factor in the sympathetic somata revealed that the staining intensity in postnatal (day 28) transgenic mice was greater than that in age-matched wild type mice. By adulthood, however, such differences in the intensities of nerve growth factor immunostaining were no longer evident. In situ hybridization analyses of trkA receptor messenger RNA revealed that levels of expression among somata of similar sizes were comparable between the transgenic and wild type neuronal populations of both postnatal day 28 and adult animals. A small subpopulation of sympathetic somata in postnatal transgenic mice displayed a marked increase in p75NTR messenger RNA expression in comparison to somata of a similar size in age-matched wild type animals. By adulthood, the proportion of sympathetic somata in the transgenic animals possessing elevated levels of p75NTR messenger RNA expression had increased. These results reveal that chronically elevated levels of endogenous nerve growth factor in the postnatal and adult mouse brain can induce both structural and neurochemical remodelling of sympathetic neurons. The preferential increase in p75NTR messenger RNA expression among sympathetic somata of transgenic mice may be required for their growth of collateral axons into the nerve growth factor-rich cerebellum during postnatal development and may facilitate the increased immunodetection of nerve growth factor on these aberrant sympathetic axons in adult transgenic animals.
authors.affiliation: Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada.
authors.forename: G E
authors.initials: GE
authors.lastname: Coome
authors.forename: M D
authors.initials: MD
authors.lastname: Kawaja
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology*; D006984:Hypertrophy; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D012016:Reference Values; D017783:Superior Cervical Ganglion / Q000378:metabolism* / Q000473:pathology*
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020917:Receptor, trkA