Amyloid beta peptide is not a candidate for the neurotrophic activities released from chromaffin cells

We have previously shown that chromaffin cells, the neuron-like cells of the adrenal medulla, release proteins, which promote in vitro survival of a large number of peripheral and central nervous system neurons (cf. Lachmund, A., Gehrke, D., Krieglstein, K. and Unsicker, K, Trophic factors from chromaffin granules promote survival of peripheral and central nervous system neurons. Neuroscience, 1994, 62, 361-370). In a search for the active molecules we are testing compounds that are known to be synthesized and released by chromaffin cells. Amyloid precursor protein (beta APP) is one of these factors (Bieger, S., Klafki, H.-W. and Unsicker, K., Synthesis and release of the beta-amyloid precursor protein by bovine chromaffin cells. Neurosci. Lett., 1993, 162, 173-175). In the present study we have investigated the possibility that amyloid beta peptide (A beta P) generated from beta APP may have survival supporting effects for neurons from embryonic chick ciliary (CG) and dorsal root ganglia (DRG). Embryonic rat hippocampal neurons, for which promotion of short-term survival by A beta P has been reported (Whitson, J. S., Selkoe, D. J. and Cotman, C. W., Amyloid beta protein enhances the survival of hippocampal neurons in vitro. Science, 1989, 243, 1488-1490), were employed as a reference. A beta P fragment 1-40, administered over a wide range of concentrations (1.5-100 micrograms/ml) did not promote the survival of CG and DRG neurons isolated from embryonic day (E) 8 chick embryos. The peptide also failed to toxically suppress survival of these neuron populations in the presence of survival promoting factors. In confirmation of previous reports, the 1-40 peptide, in comparison to the reverse 40-1 peptide, significantly enhanced survival of hippocampal neurons. These results suggest that A beta P is not a trophic factor for the peripheral neuron populations tested and most likely, not a neurotrophic component among the neurotrophic factors released by chromaffin cells.