RESUMEN
beta-Amyloid (1-40) and (25-35) have been reported to be toxic to primary cultured neurons. beta-Amyloid (1-40) was also reported to induce neurodegeneration following intracerebral injection. We attempted to replicate and extend these findings by injecting both the full length amyloid peptide and the 25-35 fragment. beta 1-40 (3 nmol in 1 microliter) or beta 25-35 (20 nmol in 2 microliters) in a vehicle of 10% DMSO (3 and 10 mM concentration, respectively) induced tissue loss and neurodegeneration. We also attempted to prevent the amyloid-induced damage by coinjecting 200 nmol of Substance P. There was no obvious reduction in the size of the lesions. Other studies, however, have reported antagonism of amyloid toxicity with tachykinin agonists. Since beta-amyloid does not appear to bind to tachykinin receptors, there is some question as to the site of the putative interaction of these peptides and, therefore, the mechanism by which beta-amyloid induces tissue damage. Our own results and published cell culture toxicity studies suggest that aggregation of the peptide and physical displacement of tissue may be responsible for both the neuronal and tissue loss, although this hypothesis is not consistent with other published findings.