Carbachol blocks beta-amyloid fragment 31-35-induced apoptosis in culturedcortical neurons

We reported previously that many neurodegenerative changes characteristic o f apoptosis could be induced by a short fragment of beta-amyloid protein, A beta 31-35, in cultured newborn mice cortical neurons, and that these chan ges were accompanied with alterations in expression of some genes. This stu dy was designed to examine whether the apoptotic processes and related gene modulations in this model could be affected by coadministration of carbach ol by electrophoretic analysis for DNA ladder formation and by RT-PCR assay s for genomic modulation. The results showed that (1) simultaneous incubati on with carbachol dose- and time-dependently blocked the specific DNA ladde r formation induced by exposure to A beta 31-35 and (2) the A beta 31-35-in duced downregulation of bcl-2 and upregulations of bax, p53, and c-fos gene s were reversed or ameliorated by the coadministration of carbachol. It is proposed that A beta 31-35-induced apoptosis can be prevented by carbachol through mechanisms that modulate the expression of related genes. (C) 2000 Elsevier Science Inc.