Nerve growth factor in the primate central nervous system: Regional distribution and ontogeny

Abstract

An enzyme immunoassay for nerve growth factor was developed to determine the regional distribution and ontogenic change in the macaque ( Macaca fascicularis) CNS. The standard curve of mouse nerve growth factor paralleled the dilution curves of extracts from the primate CNS at the adult and pre-natal stages. Furthermore, the nerve growth factor immunoreactive material comigrated with mouse nerve growth factor by means of carboxy methyl cellulose chromatography. These findings suggest that the immunoreactive material extracted from the primate CNS is mouse nerve growth factor-like molecules. At the adult stage, the highest level of nerve growth factor was in the hippocampus, with relatively high levels also in the hypothalamus, the cerebral cortex, the amygdala, the basal nucleus of Meynert, the septal nucleus, the cerebellum and the caudate nucleus. No detectable amounts were observed in the spinal cord, the substantia nigra or the dentate nucleus. In addition to the CNS, the pituitary gland contained about four times the level found in the hippocampus. At embryonic day 120, a high level of nerve growth factor already existed in the occipital cortex (80% of the level at the adult stage) and in the hippocampus (70% of the level at the adult stage). Between embryonic day 120 and the newborn stage in the occipital cortex and between embryonic day 120 and postnatal day 60 in the hippocampus, nerve growth factor levels increased about 1.7-fold, and after that, they gradually decreased until the adult stage was reached. In contrast, in the cerebellum, the level was quite high during the pre-natal period and declined to one-third at postnatal day 60. The developmental changes in nerve growth factor and choline acetyltransferase activity in the hippocampus were well correlated ( r = 0.963) between embryonic day 120 and postnatal day 60. Our studies reveal that nerve growth factor is present in the primate CNS. The high level of nerve growth factor during embyronic stages and the good correlation with choline acetyltransferase activity suggest a physiological role for nerve growth factor in the development of the primate CNS.