Regulation of the Synthesis of Nerve Growth Factor and Nerve Growth Factor Receptor

Abstract

The importance of Nerve Growth Factor (NGF) for the development and the maintenance of differentiated properties of peripheral sympathetic and neural crest- derived sensory neurons as well as for basal forebrain cholinergic neurons is well established (cf Levi-Montalcini & Angeletti, 1968; Greene & Shooter, 1980; Thoenen & Barde, 1980; Thoenen et al. 1987). NGF interacts with specific neuronal receptors, is internalized and is subsequently retrogradely transported to the perikaryon. During the last few years new methodological approaches allowed the direct analysis of the retrograde messenger function of NGF between target organs and corresponding NGF-responsive neurons. In the adult animal it was demonstrated that the density of sympathetic innervation is correlated with the levels of NGF (Korsching & Thoenen 1983) and mRNANGF (Heumann et al. 1984, Shelton & Reichardt 1984). Thus, the ratio between NGF and mRNANGF in various target tissues of sympathetic or sensory neurons is relatively constant. However, in sympathetic and sensory ganglia containing the cell bodies of NGF-responsive neurons the levels of NGF are (relatively) very high whereas the mRNANGF levels are at the detection limit (Heumann et al. 1984, Davies et al. 1987a). Similarly, in the sciatic nerve (Heumann et al. 1987a) the ratio between NGF and mRNANFG is up to 100–fold higher than in peripheral target tissues of sympathetic and sensory neurons, reflecting the very low contribution of local synthesis to the sciatic NGF content. This is in agreement with the observation that after ligation of the sciatic nerve NGF accumulates distally to the ligature whereas proximaily NGF levels are reduced to the detection limit of the NGF assay (Korsching and Thoenen, 1983b). The importance of the NGF supply from the peripheral target tissues is also demonstrated by the fact that destruction of sympathetic nerve terminals by 6–OH- dopamine results in a rapid decay of NGF levels in the sympathetic ganglia (t1/2 = 4-5 hours) (Korsching and Thoenen, 1985) with a concomitant increase of NGF in the corresponding peripheral target organs.