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 vitro (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 die five days later beta-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 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 beta-amyloid treated single cells, either in presence or in absence of ST857. beta 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 beta 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.
Scorziello
A
A
Institute of Pharmacology, School of Medicine, University of Genova, Italia.
Meucci
O
O
Calvani
M
M
Schettini
G
G
D000108:Acetylcarnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001481:Basal Metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D018698:Glutamic Acid / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D009410:Nerve Degeneration / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014741:Video Recording
D016229:Amyloid beta-Peptides; D009414:Nerve Growth Factors; D009498:Neurotoxins; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C079452:acetylcarnitine arginyl amide; D018698:Glutamic Acid; D000108:Acetylcarnitine; D001120:Arginine