ACETYL-L-CARNITINE ARGININE AMIDE PREVENTS BETA-25-35-INDUCED NEUROTOXICITY IN CEREBELLAR GRANULE CELLS

Cerebellar granule cells (CGC) at different stages of maturation in vi tro (1 or 6 DIV), were treated with beta 25-35 and acetyl-L-carnitine arginine amide (ST857) in presence of 25 mM KCl in the culture medium, and neuronal viability was assessed. Three days of treatment slightly modified the survival of 1 DIV-treated cells, which degenerate and di e five days later beta-amyloid matching. Similarly, a significative ne urotoxic effect was observed on 6 DIV treated-cells after 5 days of ex posure to the peptide, while the death occurred within 8 days. ST857 c oincubated with beta 25-35 was able to rescue neurons from beta 25-35- induced neurotoxicity. We also studied the changes in Ca2+ homeostasis following glutamate stimulation, in control and P-amyloid treated sin gle cells, either in presence or in absence of ST857. beta 25-35 did n ot affect basal [Ca2+](i), while modified glutamate-induced [Ca2+](i) increase, causing a sustained plateau phase of [Ca2+](i), that persist ed after the removal of the agonist. ST857 pretreatment completely rev erted this effect suggesting that, in CGC chronically treated with bet a 25-35, ST857 could protect the cells by neurotoxic insults of the pe ptide likely interfering with the cellular mechanisms involved in the control of Ca2+ homeostasis.