Acetyl-L-Carnitine Arginine Amide Prevents β 25–35-Induced Neurotoxicity in Cerebellar Granule Cells

Abstract

Cerebellar granule cells (CGC) at different stages of maturation in vitro (1 or 6 DIV), were treated with β 25–35 and acetyl-L-carnitine arginine amide (ST857) in presence of 25 mM KC1 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 die five days later β-amyloid matching. Similarly, a significative neurotoxic effect was observed on 6 DIV treated-cells after 5 days of exposure to the peptide, while the death occurred within 8 days. ST857 coincubated with β 25–35 was able to rescue neurons from β 25–35-induced neurotoxicity. We also studied the changes in Ca²⁺ homeostasis following glutamate stimulation, in control and β-amyloid treated single cells, either in presence or in absence of ST857. β 25–35 did not affect basal [Ca²⁺]_i, while modified glutamate-induced [Ca²⁺]_i increase, causing a sustained plateau phase of [Ca²⁺]_i, that persisted after the removal of the agonist. ST857 pretreatment completely reverted this effect suggesting that, in CGC chronically treated with β 25–35, ST857 could protect the cells by neurotoxic insults of the peptide likely interfering with the cellular mechanisms involved in the control of Ca²⁺ homeostasis.