Prolonged exposure to elevated levels of endogenous nerve growth factor affects the morphological and neurochemical features of sympathetic neurons of postnatal and adult mice

It is well documented that acute increases of target-derived nerve growth f actor affect the morphological and neurochemical features of post-ganglioni c sympathetic neurons. It has yet to be determined, however, whether simila r changes are still evident after prolonged exposure to increased levels of endogenous nerve growth factor. Using a transgenic line of mice which over expresses nerve growth factor in the brain commencing after the first week of postnatal life and continuing into adulthood, we have shown previously t hat sympathetic axons sprout into the nerve growth factor-rich cerebellum o f these animals; no such axons are seen in the cerebellum of age-matched wi ld 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 ad ult wild type mice, adult transgenic animals possessed hypertrophied gangli a 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 stru ctures 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 2 8) transgenic mice was greater than that in age-matched wild type mice. By adulthood, however, such differences in the intensities of nerve growth fac tor immunostaining were no longer evident. Insitu hybridization analyses of trkA receptor messenger RNA revealed that levels of expression among somat a of similar sizes were comparable between the transgenic and wild type neu ronal populations of both postnatal day 28 and adult animals. A small subpo pulation of sympathetic somata in postnatal transgenic mice displayed a mar ked increase in p75(NTR) messenger RNA expression in comparison to somata o f a similar size in age-matched wild type animals. By adulthood, the propor tion of sympathetic somata in the transgenic animals possessing elevated le vels of p75(NTR) messenger RNA expression had increased. These results reveal that chronically elevated levels of endogenous nerve g rowth factor in the postnatal and adult mouse brain can induce both structu ral and neurochemical remodelling of sympathetic neurons. The preferential increase in p75(NTR) messenger RNA expression among sympathetic somata of t ransgenic mice may be required for their growth of collateral axons into th e nerve growth factor-rich cerebellum during postnatal development and may facilitate the increased immunodetection of nerve growth factor on these ab errant sympathetic axons in adult transgenic animals. (C) 1999 IBRO. Publis hed by Elsevier Science Ltd.