Effects of long-term nerve growth factor deprivation on the nervous system of the adult rat: An experimental autoimmune approach

Adult rats immunized with 2.5S mouse nerve growth factor (NGF) produced antibodies which cross-reacted with rat NGF. By the criterion of ammonium sulfate precipitation followed by Sephadex G-200 chromatography, all serum anti-NGF activity was retained in the IgG fraction. Animals which developed and maintained chronic (5–6 months) serum titers of anti-NGF demonstrated a pronounced biochemical and morphological atrophy of the superior cervical ganglion which was accompanied by a 35–40% reduction in neuronal number. Norepinephrine was reduced by approximately 90% in heart and brown fat. The extent of biochemical atrophy correlated well with serum titers of anti-NGF. No effects were observed on the short adrenergic neurons of the vas deferens, adrenal medullary chromaffin cells, central adrenergic neurons, or peripheral sensory neurons. These results strongly suggest that mature peripheral sympathetic neurons remain dependent on NGF for survival as well as for maintenance.