Acetyl-L-carnitine arginine amide prevents β 25-35-induced neurotoxicity in cerebellar granule cells

• Published in: Neurochemical research Vol. 22; no. 3; pp. 257 - 265
• Main Authors: SCORZIELLO, A, MEUCCI, O, CALVANI, M, SCHETTINI, G
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.03.1997
• Subjects: Acetyl-L-carnitine; Acetylcarnitine - analogs & derivatives; Acetylcarnitine - pharmacology; Amyloid beta-Peptides - antagonists & inhibitors; Amyloid beta-Peptides - toxicity; Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Basal Metabolism; Biological and medical sciences; Cells, Cultured; Cerebellum - cytology; Cerebellum - drug effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Drug Evaluation, Preclinical; Glutamic Acid - pharmacology; Homeostasis - drug effects; Medical sciences; Nerve Degeneration - drug effects; Nerve Growth Factors - pharmacology; Neurology; Neurons - drug effects; Neurotoxins - antagonists & inhibitors; Neurotoxins - toxicity; Peptide Fragments - antagonists & inhibitors; Peptide Fragments - toxicity; Rats; Rats, Wistar; Cerebellum; Nervous system diseases; Granule neuron; Rat; Alzheimer disease; Toxicity; Rodentia; Central nervous system; Neuroprotective agent; In vitro; Cerebral disorder; Vertebrata; Mammalia; Peptide fragment; β Amyloid protein; Animal; Central nervous system disease; Degenerative disease; Brain (vertebrata)
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1023/A:1022430503520

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.