SYMPATHETIC AXONS INVADE THE BRAINS OF MICE OVEREXPRESSING NERVE GROWTH-FACTOR

Transgenic mice that overexpress nerve growth factor (NGF) in cells pr oducing glial fibrillary acidic protein were used to determine whether sympathetic axons will invade the undamaged, postnatal mammalian brai n. By using reverse transcriptase-polymerase chain reaction, NGF mRNA transgene expression was detectable in the hippocampi and cerebella of transgenic mice but not in age-matched, wild type mice. Elevated leve ls of NGF protein were detected in the hippocampi and cerebella of pos tnatal and adult transgenic animals as well as in conditioned media fr om transgenic cerebellar astrocytes in culture. The brains of these tr ansgenic mice were found to contain postganglionic sympathetic fibers, as identified by their immunohistochemical staining for tyrosine hydr oxylase and by their disappearance following superior cervical ganglio nectomy. In the cerebellum, a robust plexus of sympathetic fibers was evident in the deep white matter and in the inferior cerebellar pedunc les. These axons within the cerebellum were observed as early as 14 da ys after birth and dramatically increased in number with age. Sympathe tic axons were also associated with the large blood vessels of the hip pocampal fissure and were present within the hilar region of the denta te gyrus. NGF immunoreactivity was present within the sympathetic axon s as well as within glial cells in the transgenic cerebellum and hippo campus. Wild type mice, however, lacked similar patterns of immunostai ning. These results demonstrate that elevated expression of NGF in the intact mammalian brain results in the growth of sympathetic axons int o the central nervous system in the absence of injury. (C) 1997 Wiley- Liss, Inc.