Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation.

Abstract

The levels of nerve growth factor (NGF) and its mRNA in the rat central nervous system were determined by two‐site enzyme immunoassay and quantitative Northern blots, respectively. Relatively high NGF levels (0.4‐1.4 ng NGF/g wet weight) were found both in the regions innervated by the magnocellular cholinergic neurons of the basal forebrain (hippocampus, olfactory bulb, neocortex) and in the regions containing the cell bodies of these neurons (septum, nucleus of the diagonal band of Broca, nucleus basalis of Meynert). Comparatively low, but significant NGF levels (0.07‐0.21 ng NGF/g wet weight) were found in various other brain regions. mRNANGF was found in the hippocampus and cortex but not in the septum. This suggests that magnocellular cholinergic neurons of the basal forebrain are supplied with NGF via retrograde axonal transport from their fields of innervation. These results, taken together with those of previous studies showing that these neurons are responsive to NGF, support the concept that NGF acts as trophic factor for magnocellular cholinergic neurons.

Brain‐derived neurotrophic factor‐transduced fibroblasts: Production of BDNF and effects of grafting to the adult rat brain

“…Neurotrophin mRNA and protein as well as receptors for neurotrophins are present in the adult nervous system (Korsching et al, 1985;Shelton and Reichardt, 1986), and adult neurons are able to transport retrogradely 125 I-NGF (Schwab et al, 1979;Seiler and Schwab, 1984) and 125 I-BDNF (Wiegand et al, 1991;DiStefano et al, 1992). Neurotrophic molecules promote neuronal survival when exogenously administered in amounts that exceed normal physiological levels.…”

Rescue of lesioned septal cholinergic neurons by nerve growth factor: specificity and requirement for chronic treatment

“…The fact that NGF is synthesized by target tissues of forebrain cholinergic neurons (Korsching et al, 1985;Goedert et al, 1986;Shelton and Reichardt, 1986;Whittemore et al, 1986) and the selective localization of NGF-R on cholinergic neurons Richardson et al, 1986;Hefti and Mash, 1988;Raivich and Kreutzberg, 1987;Springer et al, 1987) strongly suggest that NGF is involved in the function of these neurons in the adult brain. However, such a physiological role has not been clearly established since its unequivocal demonstration would require "removal" of NGF from the brain.…”

“…Lesions of the septohippocampal pathway in neonatal rats result in increases of both mRNANGF and NGF in the hippocampus (Whittemore et al, 1987). In adult rats, levels of NGF mRNANGF correlate with the anatomical distribution of basal forebrain cholinergic neurons (Crutcher and Collins, 1982;Korsching et al, 1985;Goedert et al, 1986;Shelton and Reichardt, 1986;Whittemore et al, 1986). NGF receptors (NGF-R) were demonstrated in the adult brain by crosslinking iodinated NGF (Taniuchi et al, 1986b) and were visualized on forebrain cholinergic neurons in rat and human brains using autoradiographic and immunohistochemical techniques Richardson et al, 1986;Raivich and Kreutzberg, 1987;Springer et al, 1987).…”

Reduction of nerve growth factor level in the brain of genetically ataxic mice (weaver, reeler)

“…This sex-dependent difference may be peculiar to the mouse, because it is not. the ease in the rat [3]. Since NGF synthesis and accumulation in the mouse submax~1lary gIand is known to be regulated by testosterone 1191, it is expected that some kinds of sex-specific hormones may influence NGF synthesis and/or degradation in the mouse brain Eventually, normals and mutants of each sex must be examined for possible hormonal involvement in these differences.…”